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A Study of Obinutuzumab (RO5072759) Plus Chemotherapy in Comparison With Rituximab Plus Chemotherapy Followed by Obinutuzumab or Rituximab Maintenance in Patients With Untreated Advanced Indolent Non-Hodgkin's Lymphoma (GALLIUM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01332968
Recruitment Status : Active, not recruiting
First Posted : April 11, 2011
Results First Posted : June 7, 2017
Last Update Posted : June 30, 2020
Sponsor:
Collaborators:
German Low Grade Lymphoma Study Group
Institute of Cancer Research, United Kingdom
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Hodgkin's Lymphoma
Interventions Drug: Obinutuzumab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Drug: Bendamustine
Drug: Rituximab
Enrollment 1401
Recruitment Details  
Pre-assignment Details Eleven patients withdrew from the study after randomization but prior to receiving study treatment.
Arm/Group Title Rituximab+Chemotherapy - Induction Period Obinutuzumab+Chemotherapy - Induction Period Rituximab+Chemotherapy - Maintenance Period Obinutuzumab+Chemotherapy - Maintenance Period Rituximab+Chemotherapy - Observation Period Obinutuzumab+Chemotherapy - Observation Period Rituximab+Chemotherapy - Follow-Up Period Obinutuzumab+Chemotherapy - Follow-Up Period
Hide Arm/Group Description Participants received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study. Participants received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Rituximab+Chemotherapy – Observation: The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Non-responders received no protocol specified treatment during the 2-year observation period. Obinutuzumab+Chemotherapy – Observation: The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. Finally, participants were followed during a 5-year follow-up period.
Period Title: Induction Period
Started 699 702 0 0 0 0 0 0
Completed 641 646 0 0 0 0 0 0
Not Completed 58 56 0 0 0 0 0 0
Reason Not Completed
Withdrawal by Subject             3             5             0             0             0             0             0             0
Protocol Violation             3             4             0             0             0             0             0             0
Progressive disease             15             7             0             0             0             0             0             0
Physician Decision             6             1             0             0             0             0             0             0
Other             2             2             0             0             0             0             0             0
Non-compliance             1             0             0             0             0             0             0             0
Death             1             4             0             0             0             0             0             0
Adverse Event             23             26             0             0             0             0             0             0
Randomized, but not treated             4             7             0             0             0             0             0             0
Period Title: Maintenance/Observation Period
Started 0 0 612 624 12 11 0 0
Completed 0 0 399 417 2 2 0 0
Not Completed 0 0 213 207 10 9 0 0
Reason Not Completed
Withdrawal by Subject             0             0             10             5             0             0             0             0
Protocol Violation             0             0             1             1             0             0             0             0
Progressive disease             0             0             72             39             0             0             0             0
Physician Decision             0             0             14             19             0             0             0             0
Other             0             0             4             5             0             0             0             0
Non-compliance             0             0             2             3             0             1             0             0
Lost to Follow-up             0             0             1             2             0             0             0             0
Death             0             0             5             6             0             0             0             0
Adverse Event             0             0             50             65             0             0             0             0
Treatment ongoing             0             0             54             62             10             8             0             0
Period Title: Follow-Up Period
Started 0 0 0 0 0 0 542 531
Completed 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 542 531
Reason Not Completed
Death             0             0             0             0             0             0             38             22
Follow-up ongoing             0             0             0             0             0             0             502             505
Withdrawal by Subject             0             0             0             0             0             0             1             2
Lost to Follow-up             0             0             0             0             0             0             1             2
Arm/Group Title Rituximab+Chemotherapy - Induction Period Obinutuzumab+Chemotherapy - Induction Period Total
Hide Arm/Group Description Participants received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study. Participants received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study. Total of all reporting groups
Overall Number of Baseline Participants 699 702 1401
Hide Baseline Analysis Population Description
The intent-to treat (ITT) population was defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 699 participants 702 participants 1401 participants
58.1  (12.3) 58.9  (11.6) 58.5  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 699 participants 702 participants 1401 participants
Female
374
  53.5%
365
  52.0%
739
  52.7%
Male
325
  46.5%
337
  48.0%
662
  47.3%
Age Continuous in Follicular Lymphoma Sub-Population   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 699 participants 702 participants 1401 participants
57.7  (12.2) 58.2  (11.5) 57.9  (11.9)
[1]
Measure Description: Age continuous for participants with follicular lymphoma (FL) in each arm, who encompassed the population for the primary outcome measure. The FL ITT included participants in the ITT population with follicular histology (n=601 in each arm).
Gender in Follicular Lymphoma Sub-Population   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 699 participants 702 participants 1401 participants
Female 321 318 639
Male 280 283 563
[1]
Measure Description: Gender of participants with follicular lymphoma, who encompassed the population for the primary outcome measure. The FL ITT included participants in the ITT population with follicular histology (n=601 for each arm).
1.Primary Outcome
Title Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed
Hide Description Progression-free survival in participants with follicular lymphoma was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by computed tomography (CT) or magnetic resonance imaging (MRI).
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat follicular lymphoma population (FL ITT), defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
24.0 16.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab+Chemotherapy, Obinutuzumab+Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Log Rank
Comments Stratified by chemotherapy regimen and Follicular Lymphoma International Prognostic Index (FLIPI) risk group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.51 to 0.85
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-Free Survival in the Overall Study Population, Investigator-Assessed
Hide Description Progression-free survival in the overall study population was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
24.5 17.4
3.Secondary Outcome
Title Progression-Free Survival (Follicular Lymphoma Population), IRC-Assessed
Hide Description Progression-free survival in the participants with follicular lymphoma was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. In the first 170 patients with follicular lymphoma, an FDG-PET was mandatory where a PET scanner was available.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
20.8 15.5
4.Secondary Outcome
Title Progression-Free Survival (Overall Study Population), Assessed by Independent Review Committee (IRC)
Hide Description Progression-free survival in the overall study population was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
21.6 16.1
5.Secondary Outcome
Title Overall Response (Follicular Lymphoma Population), Investigator-Assessed
Hide Description Overall response in the follicular lymphoma population was defined as percentage of participants with PR or complete response CR determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with and without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Overall Response (OR) = CR + PR.
Time Frame Baseline up to end of induction period (up to approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
Without PET 86.9 88.5
With PET 81.5 85.9
6.Secondary Outcome
Title Overall Response (Overall Study Population), Investigator-Assessed
Hide Description Overall response in the overall study population was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without positron emission tomography (PET). CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%; Overall Response (OR) = CR + PR.
Time Frame Baseline up to end of induction period (up to approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
Without PET 86.1 87.6
With PET 82.1 85.7
7.Secondary Outcome
Title Complete Response (Follicular Lymphoma Population), Investigator-Assessed
Hide Description Percentage of participants with complete response in the follicular lymphoma population was determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.
Time Frame Baseline up to end of induction period (up to approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
Without PET 23.8 19.5
With PET 56.7 62.3
8.Secondary Outcome
Title Complete Response (Overall Study Population), Investigator-Assessed
Hide Description Percentage of participants with complete response in the overall study population was determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.
Time Frame Baseline up to end of induction period (up to approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
Without PET 23.2 18.9
With PET 57.3 61.4
9.Secondary Outcome
Title Overall Response (Follicular Lymphoma Population), IRC-Assessed
Hide Description Overall response in the follicular lymphoma population was defined as percentage of participants with PR or complete response CR determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Overall Response (OR) = CR + PR.
Time Frame Baseline up to end of induction period (up to approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
Without PET 88.0 91.2
With PET 85.2 88.6
10.Secondary Outcome
Title Overall Response (Overall Study Population), IRC-Assessed
Hide Description Overall response in the overall study population was defined as percentage of participants with PR or CR determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%; Overall Response (OR) = CR + PR.
Time Frame Baseline up to end of induction period (up to approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
Without PET 86.7 89.7
With PET 83.3 87.2
11.Secondary Outcome
Title Complete Response (Follicular Lymphoma Population), IRC-Assessed
Hide Description Percentage of participants with complete response in the follicular lymphoma population was determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.
Time Frame Baseline up to end of induction period (up to approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
Without PET 26.5 28.5
With PET 59.7 71.4
12.Secondary Outcome
Title Complete Response (Overall Study Population), IRC-Assessed
Hide Description Percentage of participants with complete response in the overall study population was determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.
Time Frame Baseline up to end of induction period (up to approximately 7 months)]
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
Without PET 25.9 26.9
With PET 59.4 69.5
13.Secondary Outcome
Title Overall Survival (Follicular Lymphoma Population)
Hide Description Overall survival in the follicular lymphoma population was defined as the time from the date of randomization to the date of death from any cause. Reported is the percentage of participants with event.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
7.7 5.8
14.Secondary Outcome
Title Overall Survival (Overall Study Population)
Hide Description Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. Reported is the percentage of participants with event.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
9.0 7.1
15.Secondary Outcome
Title Event-Free Survival (Follicular Lymphoma Population)
Hide Description Event-free survival in the follicular lymphoma population was defined as the time from the date of randomization to the date to disease progression/relapse, death from any cause, or initiation of a new anti-lymphoma treatment (NALT) on the basis of investigator assessment assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. Reported is the percentage of participants with an event.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
26.5 18.6
16.Secondary Outcome
Title Event-Free Survival (Overall Study Population)
Hide Description Event-free survival in the overall study population was defined as the time from the date of randomization to the date to disease progression/relapse, death from any cause, or initiation of a new anti-lymphoma treatment (NALT) on the basis of investigator assessment assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. Reported is the percentage of participants with event.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
27.0 19.7
17.Secondary Outcome
Title Disease-Free Survival (Follicular Lymphoma Population)
Hide Description Disease-free survival in the follicular lymphoma population was defined as the time from the date of the first occurrence of a documented CR to the date of disease progression/ relapse, or death from any cause for the subgroup of participants with a response of CR at any time prior to NALT on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma (RRCML). Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Reported is the percentage of participants with event.
Time Frame From first occurrence of documented CR to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with CR within the FL ITT population were included in the analysis.The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 281 298
Measure Type: Number
Unit of Measure: percentage of participants with event
11.7 9.1
18.Secondary Outcome
Title Disease-Free Survival (Overall Study Population)
Hide Description Disease-free survival in the overall study population was defined as the time from the date of the first occurrence of a documented CR to the date of disease progression/ relapse, or death from any cause for the subgroup of participants with a response of CR at any time prior to NALT on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Reported is the percentage of participants with event.
Time Frame From first occurrence of documented CR to data cut-off (up to approximately 4 years and 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with CR within the ITT population were included in the analysis.The ITT population was defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 320 343
Measure Type: Number
Unit of Measure: percentage of participants with event
12.8 8.7
19.Secondary Outcome
Title Duration of Response (DOR) (Follicular Lymphoma Population), Investigator-Assessed
Hide Description DOR was defined as the time from first occurrence of a documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR any time prior to NALT based on RRCML. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. PR was defined as >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm.
Time Frame From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with CR or PR within the FL ITT population were included in the analysis.The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 567 571
Measure Type: Number
Unit of Measure: percentage of participants with event
21.9 15.4
20.Secondary Outcome
Title Duration of Response (DOR) (Overall Study Population), Investigator-Assessed
Hide Description DOR was defined as the time from first occurrence of a documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR any time prior to NALT based on RRCML. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. PR was defined as >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm.
Time Frame From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with CR or PR within the ITT population were included in the analysis. The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 656 659
Measure Type: Number
Unit of Measure: percentage of participants with event
22.1 15.6
21.Secondary Outcome
Title Time to Next Anti-Lymphoma Treatment (Follicular Lymphoma Population)
Hide Description Time to next anti-lymphoma treatment was defined as the time from the date of randomization to the start date of the next anti-lymphoma treatment or death from any cause. Reported is the percentage of participants with event.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 601 601
Measure Type: Number
Unit of Measure: percentage of participants with event
18.5 13.3
22.Secondary Outcome
Title Time to Next Anti-Lymphoma Treatment (Overall Study Population)
Hide Description Time to next anti-lymphoma treatment was defined as the time from the date of randomization to the start date of the next anti-lymphoma treatment or death from any cause. Reported is the percentage of participants with event.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 699 702
Measure Type: Number
Unit of Measure: percentage of participants with event
19.7 14.7
23.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received any amount of any study drug and participants were analyzed according to the treatment received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 692 698
Measure Type: Number
Unit of Measure: percentage of participants
98.6 99.6
24.Secondary Outcome
Title Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population)
Hide Description FACT-G consists of the following 4 FACT-Lym sub-questionnaires: Physical Well-being (range: 0-28), Social/Family Well-being (range: 0-28), Emotional Well-being (range: 0-24) and Functional Well-being (range: 0-28). Higher scores indicate better outcomes. A positive change from baseline indicates improvement. Maint = Maintenance period.
Time Frame Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population was defined as all randomized participants with follicular histology grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study.
Participants received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 557 566
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical Well-being (PW), Baseline (n=557, n=566) 23.36  (4.77) 23.14  (4.85)
PW Change, Cycle 3, Day 1 (n=511,496) -0.91  (4.54) -0.21  (4.59)
PW Change, End Induction (n=482, 480) -0.06  (4.83) 0.56  (5.14)
PW Change, Maint Month 2 (n=362, 398) 0.83  (4.76) 1.42  (5.09)
PW Change, Maint Month 12 (n=362, 406) 1.14  (4.29) 1.34  (4.74)
PW Change, End Maint (n=352, 370) 0.86  (4.61) 1.27  (5.01)
Social/Family Well-being , Baseline (n=555, 563) 22.84  (4.92) 23.28  (4.77)
S/FW Change, Cycle 3 Day 1 (n=506, 492) -0.52  (4.03) -0.67  (3.92)
S/FW Change, End Induction (n=482, 475) -0.46  (4.77) -0.56  (5.00)
S/FW Change, Maint Month 2 (n=359, 396) -0.39  (4.72) -0.67  (4.68)
S/FW Change, Maint Month 12 (n=359, 403) -0.61  (5.56) -0.97  (5.34)
S/FW Change, End Maint (n=352, 369) -0.98  (5.64) -0.64  (5.18)
Emotional Well-being (EW), Baseline (n=556, 563) 17.64  (4.19) 17.87  (4.13)
EW Change, Cycle 3 Day 1 (n=503, 490) 1.49  (3.40) 1.35  (3.35)
EW Change, End Induction (n=478, 476) 1.16  (3.90) 1.14  (3.87)
EW Change, Maint Month 2 (n=359, 396) 1.77  (3.88) 1.49  (4.16)
EW Change, Maint Month 12 (n=360, 402) 1.45  (3.92) 1.46  (3.88)
EW Change, End Maint (n=347, 368) 1.37  (3.94) 1.49  (4.01)
Functional Well-being (FW), Baseline (n=556, 563) 18.66  (6.19) 18.76  (5.98)
FW Change, Cycle 3 Day 1 (n=504, 488) -0.30  (5.30) -0.07  (5.24)
FW Change, End Induction (n=480, 476) 0.44  (5.63) 0.93  (5.85)
FW Change, Maint Month 2 (n=359, 396) 1.04  (5.31) 1.25  (6.02)
FW Change, Maint Month 12 (n=360, 402) 1.84  (5.54) 1.65  (5.95)
FW Change, End Maint (n=348, 369) 1.37  (6.18) 1.79  (6.24)
25.Secondary Outcome
Title Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population)
Hide Description The FACT-Lym TOI Score for the follicular lymphoma population was derived from the following 3 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym TOI Score is the sum of the 3 individual subscales (range 0-116). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.
Time Frame Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population was defined as all randomized participants with follicular histology grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study.
Participants received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 559 567
Mean (Standard Deviation)
Unit of Measure: units on a scale
TOI Score, Baseline (n=559, 567) 86.61  (18.16) 86.94  (18.05)
TOI Score Change, Cycle 3 Day 1 (n=514, 497) 0.46  (15.03) 2.18  (15.95)
TOI Score Change, End Induction (n=485, 481) 2.91  (17.00) 4.57  (16.71)
TOI Score Change, Maint M2 (n=363, 400) 6.22  (16.16) 7.17  (16.57)
TOI Score Change, Maint M12 (n=362, 408) 7.61  (15.62) 7.20  (16.75)
TOI Score Change, End Maint (n=353, 373) 6.52  (17.01) 7.57  (17.28)
26.Secondary Outcome
Title Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population)
Hide Description The FACT-Lym Individual Subscale Lymphoma Score for the follicular lymphoma population was derived from the Lymphoma subscale questionnaire (range: 0-60). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.
Time Frame Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population was defined as all randomized participants with follicular histology grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study.
Participants received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 556 563
Mean (Standard Deviation)
Unit of Measure: units on a scale
Lymphoma, Baseline (n=556, 563) 45.01  (9.37) 45.54  (9.29)
Lymphoma Change, Cycle 3 Day 1 (n=509, 491) 2.04  (7.18) 2.71  (7.46)
Lymphoma Change, End Induction (n=477, 478) 2.99  (8.63) 3.01  (8.36)
Lymphoma Change, Maint Month 2 (n=360, 395) 4.80  (8.29) 4.52  (8.32)
Lymphoma Change, Maint Month 12 (n=360, 404) 4.93  (8.34) 4.27  (8.31)
Lymphoma Change, End Maint (n=350, 371) 4.45  (8.83) 4.72  (8.73)
27.Secondary Outcome
Title Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population)
Hide Description The FACT-Lym Total Score for the follicular lymphoma population was derived from the following 5 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Social/Family Well-being (range: 0-28), Emotional Well-being (range: 0-24),Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym Total Score is the sum of all 5 individual subscales (range 0-168). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.
Time Frame Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population was defined as all randomized participants with follicular histology grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study.
Participants received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, participants were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 552 559
Mean (Standard Deviation)
Unit of Measure: units on a scale
Total Score, Baseline (n=552, 559) 127.40  (22.43) 128.42  (22.16)
Total Score Change, Cycle 3 Day 1 (n=499, 484) 1.98  (17.01) 3.21  (17.12)
Total Score Change, End Induction (n=471, 471) 4.18  (19.75) 5.10  (20.03)
Total Score Change, Maint Month 2 (n=356, 392) 8.40  (19.16) 8.13  (19.80)
Total Score Change, Maint Month 12 (n=358, 396) 8.87  (19.31) 7.90  (19.55)
Total Score Change, End Maint (n=344, 366) 7.48  (19.63) 8.83  (20.84)
28.Secondary Outcome
Title Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase
Hide Description The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1. Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Completion (Compl) includes completion visit and early termination visit. Maintenance/Observation is indicated as Maint/Obs.
Time Frame Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months); Maintenance: 2, 12 months after Day 1 of last induction cycle, Follow-up: every year up to data cut-off (up to 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 558 559
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Induction (n=558, 559) 0.80  (0.24) 0.81  (0.21)
Change Baseline, Cycle 1 Day 1 (n=0, 0) NA [1]   (NA) NA [1]   (NA)
Change Baseline, Cycle 3 Day 1 (n=505, 487) 0.03  (0.21) 0.03  (0.20)
Change Baseline, Induction Compl (n=468, 466) 0.04  (0.23) 0.03  (0.22)
Change Baseline, Maint/Obs Month 2 (n=348, 377) 0.05  (0.23) 0.06  (0.22)
Change from Baseline, Maint/Obs Month 12 (n=2, 1) 0.00  (0.00) -0.20 [2]   (NA)
Change Baseline, Maint/Obs Completion (n=0, 1) NA [1]   (NA) -0.10 [2]   (NA)
[1]
NA = NE = Not estimable based on 0 participants evaluated
[2]
NA = NE = Not estimable based on 1 participant evaluated
29.Secondary Outcome
Title Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase
Hide Description The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1 Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Maintenance/Observation is indicated as Maint/Obs. Completion includes completion visit and early termination visit.
Time Frame Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months); Maintenance: 2, 12 months after Day 1 of last induction cycle, Follow-up: every year up to data cut-off (up to 4 years and 7 months)
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Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 354 395
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change Baseline, Maint/Obs Month 2 (n=11, 14) 0.04  (0.34) 0.04  (0.14)
Change Baseline, Maint/Obs Month 12 (n=354, 395) 0.06  (0.24) 0.06  (0.21)
Change Baseline, Maint/Obs Completion (n=344, 355) 0.04  (0.24) 0.05  (0.23)
30.Secondary Outcome
Title Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase
Hide Description The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1. Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Maintenance/Observation is indicated as Maint/Obs in data categories. Completion includes completion visit and early termination visit.
Time Frame Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months); Maintenance: 2, 12 after Day 1 of last induction cycle, Follow-up: every year for up to data cut-off (up to 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description:
Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
Overall Number of Participants Analyzed 149 151
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change Baseline, Follow-Up Month 36 (n=149, 151) 0.04  (0.23) 0.05  (0.25)
Change Baseline, Follow-Up Month 48 (n=26, 29) 0.07  (0.27) 0.08  (0.26)
Time Frame Baseline up to data cut-off (up to approximately 4 years and 7 months)
Adverse Event Reporting Description The safety analysis population included all participants who received any amount of any study drug and participants were analyzed according to the treatment received.
 
Arm/Group Title Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Hide Arm/Group Description Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study. Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.
All-Cause Mortality
Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   286/692 (41.33%)   340/698 (48.71%) 
Blood and lymphatic system disorders     
Anaemia  1  0/692 (0.00%)  5/698 (0.72%) 
Autoimmune haemolytic anaemia  1  1/692 (0.14%)  0/698 (0.00%) 
Bone marrow failure  1  0/692 (0.00%)  1/698 (0.14%) 
Disseminated intravascular coagulation  1  0/692 (0.00%)  1/698 (0.14%) 
Febrile Neutropenia  1  24/692 (3.47%)  34/698 (4.87%) 
Haemolysis  1  1/692 (0.14%)  0/698 (0.00%) 
Haemolytic anaemia  1  1/692 (0.14%)  0/698 (0.00%) 
Histiocytosis haematophagic  1  1/692 (0.14%)  0/698 (0.00%) 
Immune thrombocytopenic purpura  1  0/692 (0.00%)  1/698 (0.14%) 
Leukopenia  1  5/692 (0.72%)  3/698 (0.43%) 
Neutropenia  1  30/692 (4.34%)  25/698 (3.58%) 
Splenomegaly  1  1/692 (0.14%)  2/698 (0.29%) 
Thrombocytopenia  1  2/692 (0.29%)  5/698 (0.72%) 
Cardiac disorders     
Acute myocardial infarction  1  0/692 (0.00%)  4/698 (0.57%) 
Angina pectoris  1  1/692 (0.14%)  1/698 (0.14%) 
Aortic valve stenosis  1  1/692 (0.14%)  0/698 (0.00%) 
Arrhythmia  1  0/692 (0.00%)  2/698 (0.29%) 
Atrial fibrillation  1  2/692 (0.29%)  9/698 (1.29%) 
Atrial flutter  1  0/692 (0.00%)  1/698 (0.14%) 
Bradycardia  1  0/692 (0.00%)  1/698 (0.14%) 
Cardiac arrest  1  1/692 (0.14%)  1/698 (0.14%) 
Cardiac failure  1  3/692 (0.43%)  2/698 (0.29%) 
Cardiac failure congestive  1  0/692 (0.00%)  2/698 (0.29%) 
Cardio-respiratory arrest  1  0/692 (0.00%)  1/698 (0.14%) 
Cardiogenic shock  1  1/692 (0.14%)  2/698 (0.29%) 
Coronary artery disease  1  2/692 (0.29%)  0/698 (0.00%) 
Coronary artery stenosis  1  1/692 (0.14%)  0/698 (0.00%) 
Myocardial infarction  1  1/692 (0.14%)  1/698 (0.14%) 
Myocardial ischaemia  1  0/692 (0.00%)  1/698 (0.14%) 
Palpitations  1  1/692 (0.14%)  0/698 (0.00%) 
Right ventricular failure  1  0/692 (0.00%)  1/698 (0.14%) 
Sinus bradycardia  1  0/692 (0.00%)  5/698 (0.72%) 
Sinus tachycardia  1  0/692 (0.00%)  3/698 (0.43%) 
Supraventricular bradycardia  1  1/692 (0.14%)  1/698 (0.14%) 
Tachycardia  1  0/692 (0.00%)  3/698 (0.43%) 
Ventricular tachycardia  1  0/692 (0.00%)  1/698 (0.14%) 
Congenital, familial and genetic disorders     
Peroneal muscular atrophy  1  1/692 (0.14%)  0/698 (0.00%) 
Ear and labyrinth disorders     
Deafness  1  0/692 (0.00%)  1/698 (0.14%) 
Ear pain  1  1/692 (0.14%)  0/698 (0.00%) 
Eye disorders     
Corneal opacity  1  0/692 (0.00%)  1/698 (0.14%) 
Gastrointestinal disorders     
Abdominal pain  1  5/692 (0.72%)  10/698 (1.43%) 
Abdominal pain upper  1  2/692 (0.29%)  0/698 (0.00%) 
Ascites  1  2/692 (0.29%)  1/698 (0.14%) 
Colitis  1  2/692 (0.29%)  3/698 (0.43%) 
Constipation  1  1/692 (0.14%)  3/698 (0.43%) 
Diarrhoea  1  7/692 (1.01%)  11/698 (1.58%) 
Dyspepsia  1  0/692 (0.00%)  1/698 (0.14%) 
Dysphagia  1  0/692 (0.00%)  1/698 (0.14%) 
Enterovesical fistula  1  0/692 (0.00%)  1/698 (0.14%) 
Faecaloma  1  0/692 (0.00%)  1/698 (0.14%) 
Gastric haemorrhage  1  0/692 (0.00%)  1/698 (0.14%) 
Gastric ulcer  1  0/692 (0.00%)  1/698 (0.14%) 
Gastritis  1  0/692 (0.00%)  1/698 (0.14%) 
Gastritis erosive  1  1/692 (0.14%)  0/698 (0.00%) 
Gastroenteritis eosinophilic  1  1/692 (0.14%)  0/698 (0.00%) 
Gastrooesophageal reflux disease  1  1/692 (0.14%)  0/698 (0.00%) 
Haematemesis  1  0/692 (0.00%)  1/698 (0.14%) 
Haemorrhoids  1  0/692 (0.00%)  1/698 (0.14%) 
Hiatus hernia  1  1/692 (0.14%)  0/698 (0.00%) 
Ileus  1  0/692 (0.00%)  1/698 (0.14%) 
Inguinal hernia  1  0/692 (0.00%)  1/698 (0.14%) 
Intestinal ischaemia  1  0/692 (0.00%)  1/698 (0.14%) 
Intestinal obstruction  1  0/692 (0.00%)  3/698 (0.43%) 
Intestinal villi atrophy  1  1/692 (0.14%)  0/698 (0.00%) 
Large intestinal obstruction  1  1/692 (0.14%)  0/698 (0.00%) 
Large intestine polyp  1  0/692 (0.00%)  1/698 (0.14%) 
Melaena  1  0/692 (0.00%)  1/698 (0.14%) 
Mikulicz's syndrome  1  1/692 (0.14%)  0/698 (0.00%) 
Mouth ulceration  1  1/692 (0.14%)  1/698 (0.14%) 
Nausea  1  3/692 (0.43%)  6/698 (0.86%) 
Pancreatitis  1  1/692 (0.14%)  5/698 (0.72%) 
Pancreatitis acute  1  1/692 (0.14%)  1/698 (0.14%) 
Rectal haemorrhage  1  0/692 (0.00%)  1/698 (0.14%) 
Small intestinal obstruction  1  0/692 (0.00%)  2/698 (0.29%) 
Stomatitis  1  0/692 (0.00%)  1/698 (0.14%) 
Upper gastrointestinal heamorrhage  1  0/692 (0.00%)  1/698 (0.14%) 
Vomiting  1  9/692 (1.30%)  6/698 (0.86%) 
General disorders     
Adverse drug reaction  1  1/692 (0.14%)  0/698 (0.00%) 
Chest discomfort  1  0/692 (0.00%)  1/698 (0.14%) 
Chest pain  1  4/692 (0.58%)  2/698 (0.29%) 
Chills  1  3/692 (0.43%)  4/698 (0.57%) 
Cyst rupture  1  0/692 (0.00%)  1/698 (0.14%) 
Death  1  2/692 (0.29%)  1/698 (0.14%) 
General physical health deterioration  1  2/692 (0.29%)  3/698 (0.43%) 
Hyperthermia  1  1/692 (0.14%)  0/698 (0.00%) 
Ill-defined disorder  1  0/692 (0.00%)  1/698 (0.14%) 
Influenza like illness  1  1/692 (0.14%)  1/698 (0.14%) 
Injection site extravasation  1  0/692 (0.00%)  1/698 (0.14%) 
Mucosal inflammation  1  1/692 (0.14%)  1/698 (0.14%) 
Multi-organ failure  1  3/692 (0.43%)  0/698 (0.00%) 
Non-cardiac chest pain  1  0/692 (0.00%)  2/698 (0.29%) 
Oedema peripheral  1  1/692 (0.14%)  0/698 (0.00%) 
Pain  1  3/692 (0.43%)  0/698 (0.00%) 
Pyrexia  1  24/692 (3.47%)  37/698 (5.30%) 
Stent-graft endoleak  1  1/692 (0.14%)  0/698 (0.00%) 
Device breakage  1  0/692 (0.00%)  1/698 (0.14%) 
Hepatobiliary disorders     
Bile duct stenosis  1  1/692 (0.14%)  0/698 (0.00%) 
Bile duct stone  1  0/692 (0.00%)  1/698 (0.14%) 
Biliary colic  1  1/692 (0.14%)  2/698 (0.29%) 
Cholangitis  1  1/692 (0.14%)  0/698 (0.00%) 
Cholecystitis  1  6/692 (0.87%)  4/698 (0.57%) 
Cholecystitis acute  1  1/692 (0.14%)  0/698 (0.00%) 
Cholelithiasis  1  1/692 (0.14%)  1/698 (0.14%) 
Drug-induced liver injury  1  0/692 (0.00%)  2/698 (0.29%) 
Gallbladder pain  1  0/692 (0.00%)  1/698 (0.14%) 
Hepatic function abnormal  1  1/692 (0.14%)  0/698 (0.00%) 
Hepatitis acute  1  0/692 (0.00%)  1/698 (0.14%) 
Immune system disorders     
Allergy to arthropod bite  1  0/692 (0.00%)  1/698 (0.14%) 
Anaphylactic reaction  1  0/692 (0.00%)  1/698 (0.14%) 
Anaphylactic shock  1  0/692 (0.00%)  1/698 (0.14%) 
Cytokine release syndrome  1  0/692 (0.00%)  2/698 (0.29%) 
Drug hypersensitivity  1  1/692 (0.14%)  0/698 (0.00%) 
Hypersensitivity  1  3/692 (0.43%)  0/698 (0.00%) 
Hypogammaglobulinaemia  1  1/692 (0.14%)  0/698 (0.00%) 
Infections and infestations     
Abdominal abscess  1  0/692 (0.00%)  1/698 (0.14%) 
Abscess  1  1/692 (0.14%)  0/698 (0.00%) 
Abscess intestinal  1  0/692 (0.00%)  1/698 (0.14%) 
Appendicitis  1  4/692 (0.58%)  1/698 (0.14%) 
Arthritis bacterial  1  1/692 (0.14%)  0/698 (0.00%) 
Arthritis infective  1  1/692 (0.14%)  0/698 (0.00%) 
Atypical pneumonia  1  3/692 (0.43%)  1/698 (0.14%) 
Bacteraemia  1  1/692 (0.14%)  1/698 (0.14%) 
Bacterial tracheitis  1  0/692 (0.00%)  1/698 (0.14%) 
Bk virus infection  1  0/692 (0.00%)  1/698 (0.14%) 
Breast abscess  1  0/692 (0.00%)  1/698 (0.14%) 
Bronchitis  1  3/692 (0.43%)  7/698 (1.00%) 
Campylobacter infection  1  0/692 (0.00%)  1/698 (0.14%) 
Catheter site cellulitis  1  0/692 (0.00%)  1/698 (0.14%) 
Cellulitis  1  3/692 (0.43%)  3/698 (0.43%) 
Chronic sinusitis  1  0/692 (0.00%)  1/698 (0.14%) 
Clostridium difficile colitis  1  0/692 (0.00%)  1/698 (0.14%) 
Cystitis  1  0/692 (0.00%)  1/698 (0.14%) 
Cytomegalovirus infection  1  0/692 (0.00%)  1/698 (0.14%) 
Device related infection  1  3/692 (0.43%)  2/698 (0.29%) 
Device related sepsis  1  0/692 (0.00%)  1/698 (0.14%) 
Diverticulitis  1  1/692 (0.14%)  0/698 (0.00%) 
Encephalitis enteroviral  1  0/692 (0.00%)  1/698 (0.14%) 
Enterococcal infection  1  0/692 (0.00%)  1/698 (0.14%) 
Epiglottitis  1  0/692 (0.00%)  1/698 (0.14%) 
Escherichia infection  1  0/692 (0.00%)  1/698 (0.14%) 
Escherichia urinary tract infection  1  0/692 (0.00%)  1/698 (0.14%) 
Febrile infection  1  1/692 (0.14%)  0/698 (0.00%) 
Gastroenteritis  1  1/692 (0.14%)  7/698 (1.00%) 
Gastroenteritis Escherichia coli  1  0/692 (0.00%)  1/698 (0.14%) 
Gastroenteritis viral  1  1/692 (0.14%)  0/698 (0.00%) 
Herpes zoster  1  8/692 (1.16%)  7/698 (1.00%) 
Herpes zoster disseminated  1  0/692 (0.00%)  2/698 (0.29%) 
Herpes zoster infection neurological  1  1/692 (0.14%)  0/698 (0.00%) 
Herpes zoster oticus  1  0/692 (0.00%)  1/698 (0.14%) 
Infected cyst  1  0/692 (0.00%)  1/698 (0.14%) 
Infection  1  8/692 (1.16%)  6/698 (0.86%) 
Infective exacerbation of chronic obstructive airways disease  1  0/692 (0.00%)  4/698 (0.57%) 
Influenza  1  0/692 (0.00%)  3/698 (0.43%) 
Intervertebral discitis  1  1/692 (0.14%)  0/698 (0.00%) 
Lower respiratory tract infection  1  7/692 (1.01%)  12/698 (1.72%) 
Lung infection  1  6/692 (0.87%)  8/698 (1.15%) 
Mastoiditis  1  1/692 (0.14%)  0/698 (0.00%) 
Meningitis enteroviral  1  0/692 (0.00%)  1/698 (0.14%) 
Mucosal infection  1  0/692 (0.00%)  1/698 (0.14%) 
Neuroborreliosis  1  1/692 (0.14%)  0/698 (0.00%) 
Neutropenic infection  1  1/692 (0.14%)  1/698 (0.14%) 
Neutropenic sepsis  1  5/692 (0.72%)  5/698 (0.72%) 
Oesophageal candidiasis  1  0/692 (0.00%)  1/698 (0.14%) 
Oesophageal infection  1  0/692 (0.00%)  1/698 (0.14%) 
Oral herpes  1  0/692 (0.00%)  1/698 (0.14%) 
Ovarian bacterial infection  1  1/692 (0.14%)  0/698 (0.00%) 
Pelvic abscess  1  0/692 (0.00%)  1/698 (0.14%) 
Periodontitis  1  0/692 (0.00%)  1/698 (0.14%) 
Peritonsillar abscess  1  0/692 (0.00%)  1/698 (0.14%) 
Pharyngeal abscess  1  0/692 (0.00%)  1/698 (0.14%) 
Pheumocystitis jirovecii infection  1  1/692 (0.14%)  0/698 (0.00%) 
Pneumocystitis jirovecii pneumonia  1  0/692 (0.00%)  1/698 (0.14%) 
Pneumonia  1  30/692 (4.34%)  42/698 (6.02%) 
Pneumonia bacterial  1  1/692 (0.14%)  1/698 (0.14%) 
Pneumonia fungal  1  0/692 (0.00%)  1/698 (0.14%) 
Pneumonia pneumococcal  1  1/692 (0.14%)  0/698 (0.00%) 
Post procedural infection  1  1/692 (0.14%)  0/698 (0.00%) 
Pulmonary sepsis  1  0/692 (0.00%)  1/698 (0.14%) 
Pyelonephritis  1  0/692 (0.00%)  1/698 (0.14%) 
Respiratory tract infection  1  4/692 (0.58%)  5/698 (0.72%) 
Rhinitis  1  0/692 (0.00%)  1/698 (0.14%) 
Rhinovirus infection  1  0/692 (0.00%)  1/698 (0.14%) 
Sepsis  1  6/692 (0.87%)  13/698 (1.86%) 
Septic shock  1  2/692 (0.29%)  0/698 (0.00%) 
Sinusitis  1  2/692 (0.29%)  1/698 (0.14%) 
Sinusitis bacterial  1  0/692 (0.00%)  1/698 (0.14%) 
Sinusitis fungal  1  0/692 (0.00%)  1/698 (0.14%) 
Staphylococcal bacteraemia  1  0/692 (0.00%)  1/698 (0.14%) 
Staphylococcal infection  1  0/692 (0.00%)  1/698 (0.14%) 
Subcutaneous abscess  1  2/692 (0.29%)  0/698 (0.00%) 
Tuberculosis  1  0/692 (0.00%)  1/698 (0.14%) 
Tubo-ovarian abscess  1  0/692 (0.00%)  1/698 (0.14%) 
Upper respiratory tract infection  1  3/692 (0.43%)  6/698 (0.86%) 
Urinary tract infection  1  6/692 (0.87%)  9/698 (1.29%) 
Urosepsis  1  3/692 (0.43%)  3/698 (0.43%) 
Viral infection  1  3/692 (0.43%)  1/698 (0.14%) 
Viral myositis  1  0/692 (0.00%)  1/698 (0.14%) 
Injury, poisoning and procedural complications     
Accident  1  0/692 (0.00%)  1/698 (0.14%) 
Alcohol poisoning  1  0/692 (0.00%)  1/698 (0.14%) 
Anastomotic stenosis  1  0/692 (0.00%)  1/698 (0.14%) 
Ankle fracture  1  2/692 (0.29%)  1/698 (0.14%) 
Brain contusion  1  0/692 (0.00%)  1/698 (0.14%) 
Cartilage injury  1  0/692 (0.00%)  1/698 (0.14%) 
Compression fracture  1  1/692 (0.14%)  0/698 (0.00%) 
Facial bones fracture  1  1/692 (0.14%)  0/698 (0.00%) 
Fall  1  1/692 (0.14%)  3/698 (0.43%) 
Femur fracture  1  1/692 (0.14%)  2/698 (0.29%) 
Foot fracture  1  0/692 (0.00%)  1/698 (0.14%) 
Humerus fracture  1  0/692 (0.00%)  1/698 (0.14%) 
Infusion related reaction  1  18/692 (2.60%)  36/698 (5.16%) 
Ligament sprain  1  0/692 (0.00%)  1/698 (0.14%) 
Lumbar vertebral fracture  1  1/692 (0.14%)  0/698 (0.00%) 
Medication error  1  0/692 (0.00%)  1/698 (0.14%) 
Meniscus injury  1  0/692 (0.00%)  1/698 (0.14%) 
Multiple fractures  1  1/692 (0.14%)  0/698 (0.00%) 
Pneumothorax traumatic  1  0/692 (0.00%)  1/698 (0.14%) 
Seroma  1  0/692 (0.00%)  1/698 (0.14%) 
Spinal compression fracture  1  1/692 (0.14%)  1/698 (0.14%) 
Spinal fracture  1  1/692 (0.14%)  0/698 (0.00%) 
Upper limb fracture  1  3/692 (0.43%)  1/698 (0.14%) 
Investigations     
Blood creatinine increased  1  1/692 (0.14%)  1/698 (0.14%) 
Eastern cooperative oncology group performance status worsened  1  0/692 (0.00%)  1/698 (0.14%) 
Hepatic enzyme increased  1  1/692 (0.14%)  0/698 (0.00%) 
International normalised ratio increased  1  0/692 (0.00%)  1/698 (0.14%) 
Liver function test abnormal  1  0/692 (0.00%)  1/698 (0.14%) 
Metabolism and nutrition disorders     
Dehydration  1  2/692 (0.29%)  3/698 (0.43%) 
Diabetes mellitus  1  0/692 (0.00%)  2/698 (0.29%) 
Fluid overload  1  0/692 (0.00%)  1/698 (0.14%) 
Hypercalcaemia  1  2/692 (0.29%)  2/698 (0.29%) 
Hyperglycaemia  1  0/692 (0.00%)  1/698 (0.14%) 
Hypokalaemia  1  1/692 (0.14%)  1/698 (0.14%) 
Hyponatraemia  1  1/692 (0.14%)  4/698 (0.57%) 
Tumour lysis syndrome  1  1/692 (0.14%)  3/698 (0.43%) 
Musculoskeletal and connective tissue disorders     
Arthropathy  1  0/692 (0.00%)  1/698 (0.14%) 
Back pain  1  3/692 (0.43%)  2/698 (0.29%) 
Flank pain  1  1/692 (0.14%)  1/698 (0.14%) 
Haemarthrosis  1  1/692 (0.14%)  0/698 (0.00%) 
Intervertebral disc protrusion  1  1/692 (0.14%)  1/698 (0.14%) 
Muscular weakness  1  1/692 (0.14%)  0/698 (0.00%) 
Myopathy  1  1/692 (0.14%)  1/698 (0.14%) 
Myositis  1  1/692 (0.14%)  1/698 (0.14%) 
Neck pain  1  0/692 (0.00%)  1/698 (0.14%) 
Osteitis deformans  1  1/692 (0.14%)  0/698 (0.00%) 
Osteoarthritis  1  3/692 (0.43%)  2/698 (0.29%) 
Pain in extremity  1  1/692 (0.14%)  0/698 (0.00%) 
Pathological fracture  1  0/692 (0.00%)  1/698 (0.14%) 
Rotator cuff syndrome  1  0/692 (0.00%)  1/698 (0.14%) 
Spinal column stenosis  1  2/692 (0.29%)  0/698 (0.00%) 
Spinal pain  1  0/692 (0.00%)  1/698 (0.14%) 
Synovitis  1  1/692 (0.14%)  0/698 (0.00%) 
Temporomandibular joint syndrome  1  0/692 (0.00%)  1/698 (0.14%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acoustic neuroma  1  0/692 (0.00%)  1/698 (0.14%) 
Acute lymphocytic leukaemia  1  0/692 (0.00%)  1/698 (0.14%) 
Acute myeloid leukaemia  1  0/692 (0.00%)  2/698 (0.29%) 
Adenocarcinoma  1  1/692 (0.14%)  0/698 (0.00%) 
Adenocarcinoma of colon  1  0/692 (0.00%)  1/698 (0.14%) 
Adenoma benign  1  1/692 (0.14%)  0/698 (0.00%) 
Basal cell carcinoma  1  2/692 (0.29%)  5/698 (0.72%) 
Benign neoplasm  1  0/692 (0.00%)  1/698 (0.14%) 
Breast cancer  1  0/692 (0.00%)  4/698 (0.57%) 
Cancer pain  1  0/692 (0.00%)  1/698 (0.14%) 
Colon cancer  1  2/692 (0.29%)  1/698 (0.14%) 
Colorectal cancer  1  1/692 (0.14%)  0/698 (0.00%) 
Ductal adenocarcinoma of pancreas  1  1/692 (0.14%)  0/698 (0.00%) 
Gastric cancer  1  1/692 (0.14%)  0/698 (0.00%) 
Hepatic neoplasm  1  0/692 (0.00%)  1/698 (0.14%) 
Hodgkin's disease  1  0/692 (0.00%)  2/698 (0.29%) 
Hodgkin's disease nodular sclerosis  1  0/692 (0.00%)  1/698 (0.14%) 
Intraductal proliferative breast lesion  1  1/692 (0.14%)  0/698 (0.00%) 
Intraocular melanoma  1  1/692 (0.14%)  0/698 (0.00%) 
Invasive ductal breast carcinoma  1  1/692 (0.14%)  1/698 (0.14%) 
Keratoacanthoma  1  1/692 (0.14%)  0/698 (0.00%) 
Lung adenocarcinoma  1  1/692 (0.14%)  0/698 (0.00%) 
Lung neoplasm malignant  1  1/692 (0.14%)  0/698 (0.00%) 
Malignant melanoma  1  2/692 (0.29%)  1/698 (0.14%) 
Meningioma  1  0/692 (0.00%)  1/698 (0.14%) 
Myelodysplastic syndrome  1  0/692 (0.00%)  2/698 (0.29%) 
Neuroendocrine carcinoma of the skin  1  1/692 (0.14%)  0/698 (0.00%) 
Non-small cell lung cancer  1  0/692 (0.00%)  2/698 (0.29%) 
Non-small cell lung cancer stage IV  1  0/692 (0.00%)  1/698 (0.14%) 
Oesophageal carcinoma  1  0/692 (0.00%)  1/698 (0.14%) 
Oestrogen receptor positive breast cancer  1  0/692 (0.00%)  1/698 (0.14%) 
Papillary thyroid cancer  1  0/692 (0.00%)  1/698 (0.14%) 
Prostate cancer  1  3/692 (0.43%)  3/698 (0.43%) 
Rectal adenocarcinoma  1  1/692 (0.14%)  1/698 (0.14%) 
Renal cancer  1  0/692 (0.00%)  1/698 (0.14%) 
Renal cell carcinoma  1  1/692 (0.14%)  0/698 (0.00%) 
Schwannoma  1  0/692 (0.00%)  1/698 (0.14%) 
Squamous cell carcinoma  1  2/692 (0.29%)  4/698 (0.57%) 
Squamous cell carcinoma of skin  1  1/692 (0.14%)  2/698 (0.29%) 
Thyroid cancer  1  0/692 (0.00%)  1/698 (0.14%) 
Transitional cell carcinoma  1  0/692 (0.00%)  1/698 (0.14%) 
Tumour flare  1  1/692 (0.14%)  0/698 (0.00%) 
Vulvovaginal warts  1  1/692 (0.14%)  0/698 (0.00%) 
Nervous system disorders     
Ataxia  1  1/692 (0.14%)  0/698 (0.00%) 
Brachial plexopathy  1  1/692 (0.14%)  0/698 (0.00%) 
Carotid artery stenosis  1  1/692 (0.14%)  0/698 (0.00%) 
Cerebellar syndrome  1  1/692 (0.14%)  0/698 (0.00%) 
Cerebral disorder  1  0/692 (0.00%)  1/698 (0.14%) 
Cerebral haematoma  1  1/692 (0.14%)  0/698 (0.00%) 
Cerebral ischaemia  1  1/692 (0.14%)  1/698 (0.14%) 
Cerebrovascular accident  1  1/692 (0.14%)  0/698 (0.00%) 
Dementia  1  0/692 (0.00%)  1/698 (0.14%) 
Dizziness  1  2/692 (0.29%)  1/698 (0.14%) 
Dizziness postural  1  0/692 (0.00%)  1/698 (0.14%) 
Encephalopathy  1  1/692 (0.14%)  0/698 (0.00%) 
Epilepsy  1  0/692 (0.00%)  1/698 (0.14%) 
Haemorrhage intracranial  1  1/692 (0.14%)  0/698 (0.00%) 
Haemorrhagic stroke  1  1/692 (0.14%)  0/698 (0.00%) 
Hypotonia  1  0/692 (0.00%)  1/698 (0.14%) 
Ischaemic stroke  1  1/692 (0.14%)  1/698 (0.14%) 
Lethargy  1  0/692 (0.00%)  2/698 (0.29%) 
Loss of consiousness  1  0/692 (0.00%)  1/698 (0.14%) 
Monoparesis  1  0/692 (0.00%)  1/698 (0.14%) 
Nervous system disorder  1  1/692 (0.14%)  0/698 (0.00%) 
Neuralgia  1  1/692 (0.14%)  1/698 (0.14%) 
Neuropathy peripheral  1  1/692 (0.14%)  0/698 (0.00%) 
Orthostatic intolerance  1  0/692 (0.00%)  1/698 (0.14%) 
Orthostatic tremor  1  1/692 (0.14%)  0/698 (0.00%) 
Parkinson's disease  1  1/692 (0.14%)  0/698 (0.00%) 
Polyneuropathy  1  1/692 (0.14%)  0/698 (0.00%) 
Presyncope  1  3/692 (0.43%)  0/698 (0.00%) 
Seizure  1  1/692 (0.14%)  1/698 (0.14%) 
Spinal cord compression  1  0/692 (0.00%)  1/698 (0.14%) 
Syncope  1  3/692 (0.43%)  3/698 (0.43%) 
Transient ischaemic attack  1  1/692 (0.14%)  4/698 (0.57%) 
Tremor  1  1/692 (0.14%)  0/698 (0.00%) 
Subarachnoid haemorrhage  1  1/692 (0.14%)  0/698 (0.00%) 
VIIth nerve paralysis  1  0/692 (0.00%)  1/698 (0.14%) 
Pregnancy, puerperium and perinatal conditions     
Abortion  1  0/692 (0.00%)  1/698 (0.14%) 
Psychiatric disorders     
Alcohol problem  1  0/692 (0.00%)  1/698 (0.14%) 
Anxiety  1  0/692 (0.00%)  1/698 (0.14%) 
Confusional state  1  1/692 (0.14%)  1/698 (0.14%) 
Depression  1  2/692 (0.29%)  2/698 (0.29%) 
Emotional disorder  1  1/692 (0.14%)  0/698 (0.00%) 
Mental status changes  1  0/692 (0.00%)  2/698 (0.29%) 
Psychotic disorder  1  0/692 (0.00%)  1/698 (0.14%) 
Substance-induced psychotic disorder  1  1/692 (0.14%)  0/698 (0.00%) 
Suicide attempt  1  0/692 (0.00%)  1/698 (0.14%) 
Renal and urinary disorders     
Acute kidney injury  1  1/692 (0.14%)  3/698 (0.43%) 
Acute prerenal failure  1  1/692 (0.14%)  0/698 (0.00%) 
Dysuria  1  1/692 (0.14%)  0/698 (0.00%) 
Nephrolithiasis  1  0/692 (0.00%)  1/698 (0.14%) 
Renal colic  1  1/692 (0.14%)  0/698 (0.00%) 
Renal failure  1  2/692 (0.29%)  1/698 (0.14%) 
Renal infarct  1  1/692 (0.14%)  0/698 (0.00%) 
Ureteric obstruction  1  1/692 (0.14%)  1/698 (0.14%) 
Hydronephrosis  1  0/692 (0.00%)  1/698 (0.14%) 
Reproductive system and breast disorders     
Ovarian cyst  1  0/692 (0.00%)  1/698 (0.14%) 
Ovarian mass  1  0/692 (0.00%)  1/698 (0.14%) 
Prostatitis  1  2/692 (0.29%)  1/698 (0.14%) 
Vaginal ulceration  1  1/692 (0.14%)  0/698 (0.00%) 
Vulvovaginal pain  1  0/692 (0.00%)  1/698 (0.14%) 
Respiratory, thoracic and mediastinal disorders     
Acute lung injury  1  0/692 (0.00%)  1/698 (0.14%) 
Acute respiratory distress syndrome  1  0/692 (0.00%)  2/698 (0.29%) 
Acute respiratory failure  1  0/692 (0.00%)  1/698 (0.14%) 
Asthma  1  2/692 (0.29%)  2/698 (0.29%) 
Bronchospasm  1  1/692 (0.14%)  1/698 (0.14%) 
Chronic obstructive pulmonary disease  1  3/692 (0.43%)  1/698 (0.14%) 
Cough  1  2/692 (0.29%)  0/698 (0.00%) 
Dyspnoea  1  8/692 (1.16%)  10/698 (1.43%) 
Dyspnoea exertional  1  1/692 (0.14%)  0/698 (0.00%) 
Emphysema  1  0/692 (0.00%)  1/698 (0.14%) 
Epistaxis  1  1/692 (0.14%)  1/698 (0.14%) 
Haemoptysis  1  1/692 (0.14%)  0/698 (0.00%) 
Hypoxia  1  0/692 (0.00%)  2/698 (0.29%) 
Interstitial lung disease  1  4/692 (0.58%)  2/698 (0.29%) 
Lung consolidation  1  1/692 (0.14%)  0/698 (0.00%) 
Lung disorder  1  0/692 (0.00%)  1/698 (0.14%) 
Oropharyngeal pain  1  1/692 (0.14%)  0/698 (0.00%) 
Paranasal cyst  1  0/692 (0.00%)  1/698 (0.14%) 
Pharyngeal inflammation  1  0/692 (0.00%)  1/698 (0.14%) 
Pharyngeal paraesthesia  1  0/692 (0.00%)  1/698 (0.14%) 
Pleural effusion  1  5/692 (0.72%)  5/698 (0.72%) 
Pleurisy  1  0/692 (0.00%)  1/698 (0.14%) 
Pleuritic pain  1  2/692 (0.29%)  1/698 (0.14%) 
Pneumonia aspiration  1  0/692 (0.00%)  1/698 (0.14%) 
Pneumonitis  1  1/692 (0.14%)  1/698 (0.14%) 
Pneumothorax  1  0/692 (0.00%)  1/698 (0.14%) 
Productive cough  1  1/692 (0.14%)  0/698 (0.00%) 
Pulmonary arterial hypertension  1  0/692 (0.00%)  1/698 (0.14%) 
Pulmonary congestion  1  1/692 (0.14%)  0/698 (0.00%) 
Pulmonary embolism  1  2/692 (0.29%)  8/698 (1.15%) 
Respiratory arrest  1  0/692 (0.00%)  1/698 (0.14%) 
Respiratory disorder  1  1/692 (0.14%)  0/698 (0.00%) 
Respiratory failure  1  2/692 (0.29%)  3/698 (0.43%) 
Vocal cord thickening  1  1/692 (0.14%)  0/698 (0.00%) 
Pulmonary oedema  1  0/692 (0.00%)  2/698 (0.29%) 
Skin and subcutaneous tissue disorders     
Dermatitis contact  1  0/692 (0.00%)  1/698 (0.14%) 
Dermatitis exfoliative  1  0/692 (0.00%)  1/698 (0.14%) 
Rash  1  2/692 (0.29%)  5/698 (0.72%) 
Rash maculo-papular  1  1/692 (0.14%)  1/698 (0.14%) 
Swelling face  1  1/692 (0.14%)  0/698 (0.00%) 
Urticaria  1  1/692 (0.14%)  1/698 (0.14%) 
Surgical and medical procedures     
Cancer surgery  1  1/692 (0.14%)  0/698 (0.00%) 
Ileectomy  1  1/692 (0.14%)  0/698 (0.00%) 
Thyroidectomy  1  0/692 (0.00%)  1/698 (0.14%) 
Vascular disorders     
Axillary vein thrombosis  1  0/692 (0.00%)  1/698 (0.14%) 
Circulatory collapse  1  0/692 (0.00%)  1/698 (0.14%) 
Deep vein thrombosis  1  2/692 (0.29%)  1/698 (0.14%) 
Embolism  1  3/692 (0.43%)  0/698 (0.00%) 
Hypertensive crisis  1  1/692 (0.14%)  2/698 (0.29%) 
Hypotension  1  2/692 (0.29%)  7/698 (1.00%) 
Peripheral artery aneurysm  1  1/692 (0.14%)  0/698 (0.00%) 
Peripheral ischaemia  1  0/692 (0.00%)  1/698 (0.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   663/692 (95.81%)   679/698 (97.28%) 
Blood and lymphatic system disorders     
Anaemia  1  65/692 (9.39%)  65/698 (9.31%) 
Leukopenia  1  80/692 (11.56%)  81/698 (11.60%) 
Neutropenia  1  285/692 (41.18%)  328/698 (46.99%) 
Thrombocytopenia  1  48/692 (6.94%)  84/698 (12.03%) 
Gastrointestinal disorders     
Abdominal pain  1  68/692 (9.83%)  68/698 (9.74%) 
Abdominal pain upper  1  41/692 (5.92%)  52/698 (7.45%) 
Constipation  1  205/692 (29.62%)  239/698 (34.24%) 
Diarrhoea  1  150/692 (21.68%)  183/698 (26.22%) 
Dyspepsia  1  42/692 (6.07%)  59/698 (8.45%) 
Nausea  1  312/692 (45.09%)  330/698 (47.28%) 
Stomatitis  1  50/692 (7.23%)  53/698 (7.59%) 
Vomiting  1  134/692 (19.36%)  160/698 (22.92%) 
General disorders     
Asthenia  1  36/692 (5.20%)  32/698 (4.58%) 
Chest discomfort  1  37/692 (5.35%)  42/698 (6.02%) 
Chills  1  71/692 (10.26%)  120/698 (17.19%) 
Fatigue  1  247/692 (35.69%)  259/698 (37.11%) 
Mucosal inflammation  1  40/692 (5.78%)  30/698 (4.30%) 
Oedema peripheral  1  33/692 (4.77%)  39/698 (5.59%) 
Pyrexia  1  141/692 (20.38%)  187/698 (26.79%) 
Infections and infestations     
Bronchitis  1  34/692 (4.91%)  43/698 (6.16%) 
Herpes zoster  1  39/692 (5.64%)  64/698 (9.17%) 
Lower respiratory tract infection  1  66/692 (9.54%)  54/698 (7.74%) 
Nasopharyngitis  1  120/692 (17.34%)  117/698 (16.76%) 
Oral herpes  1  36/692 (5.20%)  39/698 (5.59%) 
Respiratory tract infection  1  31/692 (4.48%)  35/698 (5.01%) 
Rhinitis  1  32/692 (4.62%)  46/698 (6.59%) 
Sinusitis  1  42/692 (6.07%)  67/698 (9.60%) 
Upper respiratory tract infection  1  119/692 (17.20%)  125/698 (17.91%) 
Urinary tract infection  1  57/692 (8.24%)  67/698 (9.60%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  333/692 (48.12%)  405/698 (58.02%) 
Investigations     
Weight decreased  1  38/692 (5.49%)  33/698 (4.73%) 
Metabolism and nutrition disorders     
Decreased appetite  1  77/692 (11.13%)  87/698 (12.46%) 
Hypokalaemia  1  25/692 (3.61%)  44/698 (6.30%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  88/692 (12.72%)  103/698 (14.76%) 
Back pain  1  108/692 (15.61%)  94/698 (13.47%) 
Bone pain  1  37/692 (5.35%)  36/698 (5.16%) 
Muscle spasms  1  36/692 (5.20%)  37/698 (5.30%) 
Myalgia  1  30/692 (4.34%)  47/698 (6.73%) 
Pain in extremity  1  56/692 (8.09%)  63/698 (9.03%) 
Nervous system disorders     
Dizziness  1  49/692 (7.08%)  66/698 (9.46%) 
Dysgeusia  1  55/692 (7.95%)  60/698 (8.60%) 
Headache  1  114/692 (16.47%)  138/698 (19.77%) 
Neuropathy peripheral  1  48/692 (6.94%)  49/698 (7.02%) 
Paraesthesia  1  45/692 (6.50%)  56/698 (8.02%) 
Peripheral sensory neuropathy  1  47/692 (6.79%)  55/698 (7.88%) 
Psychiatric disorders     
Anxiety  1  27/692 (3.90%)  36/698 (5.16%) 
Insomnia  1  78/692 (11.27%)  104/698 (14.90%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  163/692 (23.55%)  194/698 (27.79%) 
Dyspnoea  1  84/692 (12.14%)  106/698 (15.19%) 
Oropharyngeal pain  1  69/692 (9.97%)  76/698 (10.89%) 
Productive cough  1  27/692 (3.90%)  35/698 (5.01%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  75/692 (10.84%)  88/698 (12.61%) 
Dry skin  1  33/692 (4.77%)  38/698 (5.44%) 
Erythema  1  32/692 (4.62%)  37/698 (5.30%) 
Pruritus  1  89/692 (12.86%)  91/698 (13.04%) 
Rash  1  120/692 (17.34%)  113/698 (16.19%) 
Vascular disorders     
Flushing  1  39/692 (5.64%)  46/698 (6.59%) 
Hypertension  1  45/692 (6.50%)  53/698 (7.59%) 
Hypotension  1  23/692 (3.32%)  40/698 (5.73%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01332968    
Other Study ID Numbers: BO21223
2010-024132-41 ( EudraCT Number )
First Submitted: April 8, 2011
First Posted: April 11, 2011
Results First Submitted: February 3, 2017
Results First Posted: June 7, 2017
Last Update Posted: June 30, 2020