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CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 1a)

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ClinicalTrials.gov Identifier: NCT01010061
Recruitment Status : Completed
First Posted : November 9, 2009
Results First Posted : April 1, 2014
Last Update Posted : September 14, 2018
Sponsor:
Collaborators:
German CLL Study Group
Genentech, Inc.
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 Lymphocytic Leukemia, Chronic
Interventions Drug: obinutuzumab
Drug: rituximab
Drug: chlorambucil
Enrollment 787
Recruitment Details 787 patients were enrolled in the study. Following a 6 patient safety run-in prior to randomization, 781 patients were randomized.
Pre-assignment Details 589 patients were randomized to 1 of 3 treatment groups in 2:2:1 ratio: GClb (n=238), RClb (n=233) or Clb (n=118) in Stage 1 and an additional 192 randomized to GClb or RClb in Stage 2 [NCT02053610]. Stage 1 was divided for analysis into: Stage 1a (GClb vs Clb) n=356 reported here and Stage 1b (RClb vs Clb) [NCT01998880] reported separately.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [First infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Period Title: Overall Study
Started 238 118
Received Study Drug 236 116
Completed 190 [1] 78
Not Completed 48 40
Reason Not Completed
Adverse Events or Intercurrent Illness             33             16
Disease Progression             2             8
Withdrew Consent             5             1
Death             3             6
Administrative/Other             0             1
Refused Treatment/Did Not Cooperate             2             0
Insufficient Therapeutic Response             1             5
Violation of Selection Criteria             0             1
Did Not Receive Treatment             2             2
[1]
Completed=Completed treatment.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb) Total
Hide Arm/Group Description Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [First infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil. Total of all reporting groups
Overall Number of Baseline Participants 238 118 356
Hide Baseline Analysis Population Description
Baseline measures are based on the participants who were included in the Stage 1a analysis.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 238 participants 118 participants 356 participants
<65 years 42 26 68
>=65 years 196 92 288
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 118 participants 356 participants
Female
98
  41.2%
43
  36.4%
141
  39.6%
Male
140
  58.8%
75
  63.6%
215
  60.4%
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by the investigator. Progressive disease (PD) required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels >20 g/L or <10 g/dL or a decrease of platelet counts >50% or <100 x 10^9/L or by a decrease of neutrophil counts >50% or <1.0 x 10^9/L).
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants. Patients without PFS events were censored.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Median (95% Confidence Interval)
Unit of Measure: Months
31.1
(26.5 to 35.6)
11.1
(10.7 to 11.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obinutuzumab + Chlorambucil (GClb), Chlorambucil (Clb)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Type I error controlled through closed test procedure.
Method Log Rank, Stratified
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.16 to 0.28
Estimation Comments Stratified by Binet stage at Baseline.
2.Primary Outcome
Title Percentage of Participants With Progression Free Survival Events
Hide Description Percentage of Participants with Progression Free Survival Events: disease progression, relapse, or death.
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Measure Type: Number
Unit of Measure: Percentage of participants
72.7 90.7
3.Secondary Outcome
Title Progression Free Survival Based on Independent Review Committee (IRC) Data
Hide Description PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by Independent Review Committee. Progressive disease required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels >20 g/L or <10 g/dL or a decrease of platelet counts >50% or <100 x 10^9/L or by a decrease of neutrophil counts >50% or <1.0 x 10^9/L).
Time Frame Randomization to clinical cutoff date of 9 May 2013 (median observation 22.8 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants. Patients without PFS events were censored.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Median (95% Confidence Interval)
Unit of Measure: Months
27.2
(23.5 to 33.0)
11.2
(11.0 to 12.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obinutuzumab + Chlorambucil (GClb), Chlorambucil (Clb)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank, Stratified
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.14 to 0.27
Estimation Comments Stratified by Binet stage at Baseline.
4.Secondary Outcome
Title Percentage of Participants With Progression Free Survival Events Based on Independent Review Committee (IRC) Data
Hide Description Percentage of Participants with Progression Free Survival Events: progression, relapse, or death from any cause as assessed by an Independent Review Committee.
Time Frame Randomization to clinical cutoff date of 9 May 2013 (median observation 22.8 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants. Participants without PFS events were censored.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Measure Type: Number
Unit of Measure: Percentage of participants
37.4 76.3
5.Secondary Outcome
Title Percentage of Participants With End of Treatment Response (EOTR)
Hide Description EOTR was the first response assessment 56 days from the last dose according to the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) guidelines. CR required: Peripheral blood lymphocytes below 4 x 10^9/L, Absence of significant lymphadenopathy, No hepatomegaly, No splenomegaly, Absence of disease, Blood counts above the following values (Neutrophils >1.5 x 10^9/L, Platelets >100 x 10^9/L, Hemoglobin >11g/dL) and Bone marrow at least normocellular for age. CRi was CR with incomplete bone marrow recovery. PR required the following for at least 2 months from end of treatment: ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value AND Either a ≥ 50% reduction in lymphadenopathy OR ≥50% reduction of liver enlargement OR ≥50% reduction of spleen enlargement PLUS at least one of the following: Neutrophils >1.5 x 10^9/ or ≥50% increase, Platelets >100 x 10^9/L or ≥50% increase, Hemoglobin 11 g/dL or ≥50% increase.
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants) with data available for analysis. Participants who did not reach the 3 month Follow-up visit at the time of the clinical cutoff are excluded.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Complete Response (CR)
17.2
(12.7 to 22.6)
0.0
(0.0 to 3.1)
Complete Response incomplete (CRi)
4.2
(2 to 7.6)
0.0
(0.0 to 3.1)
Partial Response (PR)
48.3
(41.8 to 54.9)
28.8
(20.8 to 37.9)
Nodular Partial Response (nPR)
7.6
(4.5 to 11.7)
2.5
(0.5 to 7.3)
Stable Disease
5
(2.6 to 8.6)
22.9
(15.7 to 31.5)
Progressive Disease
4.2
(2.0 to 7.6)
28.8
(20.8 to 37.9)
No Response Assessment
13.4 [1] 
(NA to NA)
16.9 [1] 
(NA to NA)
[1]
95% CI not estimated.
6.Secondary Outcome
Title Percentage of Participants With Best Overall Response
Hide Description Best overall response according to IWCLL guidelines was defined as the percentage of patients with CR, CRi,PR or nPR. CR required all of the following: Peripheral blood lymphocytes below 4 x 10^9/L, Absence of significant lymphadenopathy, No hepatomegaly, No splenomegaly, Absence of disease, Blood counts above the following values (Neutrophils >1.5 x 10^9/L, Platelets >100 x 10^9/L, Hemoglobin >11g/dL) and Bone marrow at least normocellular for age. CRi was CR with incomplete bone marrow recovery. PR required the following for at least 2 months from end of treatment: ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value AND Either a ≥ 50% reduction in lymphadenopathy OR ≥50% reduction of liver enlargement OR ≥50% reduction of spleen enlargement PLUS at least one of the following: Neutrophils >1.5 x 10^9/ or ≥50% increase, Platelets >100 x 10^9/L or ≥50% increase, Hemoglobin 11 g/dL or ≥50% increase.
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants) with data available for analysis. Participants who did not reach the 3 month Follow-up visit at the time of the clinical cutoff are excluded.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Complete Response (CR)
26.5
(21.0 to 32.6)
0.0
(0 to 3.1)
Complete Response incomplete (CRi)
2.5
(0.9 to 5.4)
1.7
(0.2 to 6)
Partial Response (PR)
47.1
(40.6 to 53.6)
31.4
(23.1 to 40.5)
Nodular Partial Response (nPR)
2.1
(0.7 to 4.8)
0
(0 to 3.1)
Stable Disease
4.2
(2 to 7.6)
21.2
(14.2 to 29.7)
Progressive Disease
4.2
(2.0 to 7.6)
28.8
(20.8 to 37.9)
No Response Assessment
13.4 [1] 
(NA to NA)
16.9 [1] 
(NA to NA)
[1]
95% CI was not estimated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obinutuzumab + Chlorambucil (GClb), Chlorambucil (Clb)
Comments Includes subjects with best overall response: CR, CRi, PR or nPR.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 45.1
Confidence Interval (2-Sided) 95%
34.7 to 55.5
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Event Free Survival
Hide Description Event-free survival (EFS) was defined as the time between date of randomization and the date of disease progression/relapse, death, or start of a new anti-leukemic therapy. Progressive disease as per IWCLL criteria required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels >20 g/L or <10 g/dL or a decrease of platelet counts >50% or <100 x 10^9/L or by a decrease of neutrophil counts >50% or <1.0 x 10^9/L).
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants. Patients without EFS events were censored.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Median (95% Confidence Interval)
Unit of Measure: Months
28.7
(23.9 to 32.9)
10.8
(8.0 to 11.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obinutuzumab + Chlorambucil (GClb), Chlorambucil (Clb)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank, Stratified
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.15 to 0.26
Estimation Comments Stratified by Binet stage at Baseline.
8.Secondary Outcome
Title Overall Survival
Hide Description Overall Survival (OS) was defined as the time between the date of randomization and the date of death due to any cause.
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants. Patients without OS events were censored.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(74.2 to NA)
66.7 [2] 
(50.9 to NA)
[1]
The median survival time and upper limit of 95% CI could not be estimated due to a low number of deaths.
[2]
The upper limit of 95% CI could not be estimated due to a low number of deaths.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obinutuzumab + Chlorambucil (GClb), Chlorambucil (Clb)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0196
Comments [Not Specified]
Method Log Rank, Stratified
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.49 to 0.94
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Duration of Response
Hide Description Duration of Response was defined as the date the response [either Complete Response (CR) or Partial Response (PR)] was first recorded until the date of Disease Progression or death due to any cause. Response was assessed according IWCLL guidelines.
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants) with CR or PR. Participants without response were censored.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 191 41
Median (95% Confidence Interval)
Unit of Measure: Months
24.8
(22.1 to 33.5)
5.1
(3.3 to 6.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obinutuzumab + Chlorambucil (GClb), Chlorambucil (Clb)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank, Stratified
Comments Stratified by Binet stage at Baseline.
Method of Estimation Estimation Parameter Hazard Ratio (stratified)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.13 to 0.28
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With Molecular Remission at the End of Treatment
Hide Description Molecular remission was defined as a minimal residual disease (MRD)-negative result at the end of treatment (assessment that occurred between 56 days and 6 months of last treatment). Molecular remission was assessed for all patients using a blood sample. Additionally, a bone marrow sample was obtained from patients whom the investigator assumed to have a complete response, consistent with the IWCLL guidelines. A combined analysis of blood and bone marrow results was conducted. A patient was considered MRD negative if result was less than 1 chronic lymphocytic leukemia (CLL) cell in 10000 leukocytes (MRD value < 0.0001) based on the method of allele specific polymerase chain reaction (ASO-PCR).
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants) with data available for analysis. Participants who did not reach the 3 month Follow-up visit at the time of the clinical cutoff are excluded.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 166 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
25
(18.9 to 32.6)
0
(0.0 to 4.0)
11.Secondary Outcome
Title Time to Re-Treatment/New-antileukemic Therapy
Hide Description Time to re-treatment/new anti-leukemic therapy was defined as time between the date of randomization and the date of first intake of re-treatment or new anti-leukemic therapy.
Time Frame Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants. Participants without events (re-treatment or new anti-leukemic therapy) were censored.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Median (95% Confidence Interval)
Unit of Measure: Months
55.7 [1] 
(47.4 to NA)
15.1
(11.7 to 18.0)
[1]
The upper level of the 95% CI was not reached.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obinutuzumab + Chlorambucil (GClb), Chlorambucil (Clb)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank, Stratified
Comments Stratified by Binet stage at Baseline.
Method of Estimation Estimation Parameter Hazard Ratio (stratified)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.19 to 0.35
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Pharmacokinetics of Obinutuzumab (RO5072759) in Combination With Chlorambucil (Clb)
Hide Description Blood samples were collected from all patients allocated to the GClb treatment arm pre- and post-dose Day 1 of Cycles 1 to 6 and were sent to a laboratory. The concentration of obinutzumab in serum was determined using a validated enzyme-linked immunosorbent assay (ELISA) and was reported in micrograms/milliliter (μg/mL).
Time Frame Pre- and post-dose sampling on day 1 of cycles 1-6 (Up to 26.8 months)
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Hide Analysis Population Description
PK population includes all participants with PK data available at the given time-point.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb)
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Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [First infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Overall Number of Participants Analyzed 220
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
Post-dose Cycle 1 (n=201)
247
(41.6%)
Pre-dose Cycle 2 (n=198)
227
(57.9%)
Post-dose Cycle 2 (n=197)
587
(36.5%)
Pre-dose Cycle 3 (n=193)
165
(68.7%)
Post-dose Cycle 3 (n=192)
527
(39.7%)
Pre-dose Cycle 4 (n=191)
156
(74.3%)
Post-dose Cycle 4 (n=189)
535
(41.0%)
Pre-dose Cycle 5 (n=185)
163
(72.4%)
Post-dose Cycle 5 (n=181)
534
(39.1%)
Pre-dose Cycle 6 (n=185)
181
(69.0%)
Post-dose Cycle 6 (n=183)
525
(39.6%)
13.Secondary Outcome
Title European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire Score
Hide Description The EORTC Quality of Life Questionnaire QLQ-C30 was used to assess patient-reported outcomes (PRO) and symptom burden. The QLQ-C30 contains 30 items including the functional scales of physical functioning (5 items), role functioning (2 items), emotional functioning (4 items), cognitive functioning (2 items), social functioning (2 items) and symptom scales including fatigue (3 items), nausea and vomiting (2 items), and pain (4 items) and six single item scales on dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact. Final scores are transformed such that they range from 0 − 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 − 10 points considered to be of minimally important difference to participants. A positive change from Baseline indicated improvement.
Time Frame Baseline and Cycle 4 Day 1 (Cy4D1)
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Hide Analysis Population Description
ITT population. Here, n signifies the number of participants who were evaluated for specified categories.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [First infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Mean (Standard Deviation)
Unit of Measure: unit on a scale
Appetite Loss Scale: Baseline (n=226, 111) 18.1  (28.46) 19.8  (29.26)
Appetite Loss Scale: Cy4D1 (n=189, 92) 10.2  (21.77) 14.5  (24.36)
Cognitive Functioning Scale: Baseline (n=227, 111) 80.6  (21.35) 81.8  (22.76)
Cognitive Functioning Scale:Cy4D1 (n=190,93) 83.9  (20.31) 85.8  (18.54)
Constipation Scale: Baseline (n=225, 111) 14.8  (23.94) 16.8  (26.92)
Constipation Scale: Cy4D1 (n=188, 93) 15.1  (25.16) 12.5  (23.53)
Diarrhoea Scale: Baseline (n=226, 110) 9.3  (20.05) 8.8  (18.98)
Diarrhoea Scale: Cy4D1 (n=189, 93) 9.3  (19.47) 6.5  (14.95)
Dyspnoea Scale: Baseline (n=225, 109) 27.1  (29.89) 23.9  (27.63)
Dyspnoea: Cy4D1 (n=189, 91) 15.9  (23.71) 22.3  (26.78)
Emotional Functioning Scale: Baseline (n=226, 111) 73.8  (23.45) 72.9  (25.7)
Emotional Functioning Scale: Cy4D1(n=190,93) 82.5  (18.62) 80.6  (18.48)
Fatigue Scale: Baseline (n=226, 111) 38  (25.72) 36.9  (27.01)
Fatigue Scale: Cy4D1(n=189, 93) 29.2  (20.39) 30.8  (23.00)
Financial Difficulties Scale: Baseline (n=224,110) 8.9  (20.69) 13.6  (25.26)
Financial Difficulty Scale: Cy4D1(n=189,93) 7.4  (17.64) 9.3  (19.88)
Nausea, Vomiting Scale: Baseline (n=227, 111) 5  (11.18) 7.4  (18.49)
Nausea, Vomiting Scale: Cy4D1 (n=189,93) 5.5  (11.51) 7.5  (17.81)
Pain scale: Baseline (n=228, 111) 22.9  (27.57) 21.5  (25.66)
Pain scale: Cy4D1 (n=190, 93) 17.9  (24.09) 17.7  (25.98)
Physical Functioning Scale: Baseline (n=228, 111) 73.7  (19.86) 77.3  (18.87)
Physical Functioning Scale: Cy4D1(n=189,93) 78.6  (18.71) 80.9  (16.24)
Global Health Status Scale: Baseline (n=226, 111) 58.4  (22.8) 57.4  (22.9)
Global Health Status Scale: Cy4D1(n=189,93) 66.7  (20.03) 63.4  (20.56)
Role Functioning Scale: Baseline(n=227,110) 76.1  (26.18) 74.7  (28.35)
Role Functioning Scale: Cy4D1(n=189,93) 79.7  (23.64) 81.5  (21.35)
Social Functioning Scale:Baseline(n=226,110) 86.3  (22.52) 83.3  (25.34)
Social Functioning Scale: Cy4D1(n=190,93) 87.8  (19.97) 85.5  (19.38)
Insomnia Scale: Baseline (n=228,111) 29.4  (31.12) 31.5  (32.98)
Insomnia Scale: Cy4D1(n=189,93) 20.6  (27.13) 24.4  (29.13)
14.Secondary Outcome
Title European Organization for Research and Treatment of Cancer (EORTC) QLQ-CLL16 Questionnaire Score
Hide Description EORTC Quality of Life Questionnaire (QLQ-CLL16) module was used to assess patient-reported outcomes and symptom burden. The QLQ-CLL16 module includes three multi-item scales assessing fatigue (2 items), treatment side effects and disease symptoms (8 items), infection (4 items) and two single item scales on social activities and future health worries. Final scores are transformed such that they range from 0 − 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 − 10 points considered to be of minimally important difference to participants. A positive change from Baseline indicated improvement.
Time Frame Baseline and Cycle 4 Day 1 (Cy4D1)
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Hide Analysis Population Description
ITT population. Here, n signifies the number of participants who were evaluated for specified categories.
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb)
Hide Arm/Group Description:
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [First infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
Overall Number of Participants Analyzed 238 118
Mean (Standard Deviation)
Unit of Measure: unit on a scale
Disease Effects Scale: Baseline (n=209, 102) 23  (18.89) 23.7  (20.18)
Disease Effects Scale: Cy4D1 (n=176, 86) 15.0  (15.12) 15.9  (14.16)
Fatigue Scale: Baseline (n=209, 102) 31.2  (25.83) 27.6  (24.65)
Fatigue Scale: Cy4D1 (n=176, 86) 20.9  (21.51) 23.4  (22.20)
Future Health: Baseline (n=206, 101) 47.7  (32.14) 50.8  (33.53)
Future Health: Cy4D1 (n=175, 86) 29.5  (31.74) 39.1  (30.33)
Infection Scale: Baseline (n=209, 102) 12  (15.91) 14.6  (17.97)
Infection Scale: Cy4D1 (n=176, 86) 8.9  (11.65) 8.5  (10.70)
Social Problems: Baseline (n=206, 100) 24.3  (31.99) 26.3  (33.26)
Social Problems: Cy4D1 (n=175, 85) 19.4  (27.75) 22.0  (27.00)
Treatment Side Effects Scale: Baseline (n=209,102) 19.8  (17.7) 17.2  (15.27)
Treatment Side Effect Scale: Cy4D1(n=176,86) 14.7  (14.68) 15.6  (16.11)
Time Frame Randomization to clinical cutoff (median observation 42 months)
Adverse Event Reporting Description Safety population included patients who received at least 1 dose of study drug. Adverse Events are reported for Stage 1a (GClb and Clb arms). In Stage 1a, 4 patients randomized to the RClb arm actually received obinutuzumab and were included in the GClb arm for analysis.
 
Arm/Group Title Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb) Crossover Subjects: Obinutuzumab + Chlorambucil (GClb)
Hide Arm/Group Description Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil. Subjects in Clb arm who progressed during/within 6 months after end of Clb treatment had opportunity to cross over to GClb arm at discretion of investigator. Subjects received 1000 mg obinutuzumab IV infusion, on Day 1 [First infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 of Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 milligram per kilogram of body weight (mg/kg) orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
All-Cause Mortality
Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb) Crossover Subjects: Obinutuzumab + Chlorambucil (GClb)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb) Crossover Subjects: Obinutuzumab + Chlorambucil (GClb)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   113/241 (46.89%)   45/116 (38.79%)   8/30 (26.67%) 
Blood and lymphatic system disorders       
Febrile neutropenia  1  2/241 (0.83%)  5/116 (4.31%)  1/30 (3.33%) 
Anaemia  1  3/241 (1.24%)  0/116 (0.00%)  0/30 (0.00%) 
Autoimmune haemolytic anaemia  1  1/241 (0.41%)  2/116 (1.72%)  0/30 (0.00%) 
Neutropenia  1  3/241 (1.24%)  0/116 (0.00%)  0/30 (0.00%) 
Thrombocytopenia  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Haemolysis  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Haemolytic anaemia  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Immune thrombocytopenic purpura  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Pancytopenia  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Cardiac disorders       
Myocardial infarction  1  4/241 (1.66%)  2/116 (1.72%)  0/30 (0.00%) 
Cardiac failure  1  3/241 (1.24%)  2/116 (1.72%)  0/30 (0.00%) 
Atrial fibrillation  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Acute coronary syndrome  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Atrial thrombosis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Cardiac failure congestive  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Nodal rhythm  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Tachyarrhythmia  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Congenital, familial and genetic disorders       
Hereditary non-polyposis colorectal cancer syndrome  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Phimosis  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Abdominal pain  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Ascites  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Colitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Enterocolitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Gastritis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Inguinal hernia  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Pancreatitis  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Pancreatitis acute  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Thrombosis mesenteric vessel  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Ileus  1  0/241 (0.00%)  0/116 (0.00%)  1/30 (3.33%) 
General disorders       
Chest pain  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Asthenia  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Death  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Fatigue  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
General physical health deterioration  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Impaired healing  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Malaise  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Pyrexia  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Hepatobiliary disorders       
Biliary colic  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Cholecystitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Cholelithiasis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Liver disorder  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Immune system disorders       
Anaphylactic reaction  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Infections and infestations       
Pneumonia  1  10/241 (4.15%)  4/116 (3.45%)  1/30 (3.33%) 
Respiratory tract infection  1  2/241 (0.83%)  3/116 (2.59%)  0/30 (0.00%) 
Septic shock  1  2/241 (0.83%)  2/116 (1.72%)  0/30 (0.00%) 
Urinary tract infection  1  3/241 (1.24%)  1/116 (0.86%)  0/30 (0.00%) 
Erysipelas  1  1/241 (0.41%)  2/116 (1.72%)  0/30 (0.00%) 
Lower respiratory tract infection  1  2/241 (0.83%)  1/116 (0.86%)  0/30 (0.00%) 
Neutropenic sepsis  1  3/241 (1.24%)  0/116 (0.00%)  0/30 (0.00%) 
Sepsis  1  0/241 (0.00%)  4/116 (3.45%)  1/30 (3.33%) 
Infection  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Liver abscess  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Upper respiratory tract infection  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Bronchitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Cellulitis  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Dacryocystitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Diverticulitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Endocarditis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Epididymitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Escherichia sepsis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Gangrene  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Infective exacerbation of bronchiectasis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Intervertebral discitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Lung infection  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Neutropenic infection  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Ophthalmic herpes zoster  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Oral candidiasis  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Staphylococcal sepsis  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Stenotrophomonas sepsis  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Subcutaneous abscess  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Superinfection bacterial  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Wound infection  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Gastroenteritis  1  0/241 (0.00%)  0/116 (0.00%)  1/30 (3.33%) 
Injury, poisoning and procedural complications       
Infusion related reaction  1  27/241 (11.20%)  0/116 (0.00%)  0/30 (0.00%) 
Tibia fracture  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Femoral neck fracture  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Fracture displacement  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Spinal fracture  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Subdural haematoma  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Subdural haemorrhage  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Tendon rupture  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Radius Fracture  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Investigations       
Platelet count decreased  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Metabolism and nutrition disorders       
Tumour lysis syndrome  1  3/241 (1.24%)  0/116 (0.00%)  0/30 (0.00%) 
Dehydration  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Hyperglycaemia  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Musculoskeletal chest pain  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Spinal column stenosis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  7/241 (2.90%)  0/116 (0.00%)  1/30 (3.33%) 
Squamous cell carcinoma of skin  1  6/241 (2.49%)  0/116 (0.00%)  0/30 (0.00%) 
Lung adenocarcinoma  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Malignant melanoma  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Pancreatic carcinoma  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Plasma cell myeloma  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Prostate cancer  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Squamous cell carcinoma  1  3/241 (1.24%)  1/116 (0.86%)  0/30 (0.00%) 
Adenocarcinoma gastric  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Adenocarcinoma of colon  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Choroid melanoma  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Colon cancer  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Gastrointestinal stromal tumour  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Hepatocellular carcinoma  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Intraocular melanoma  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Keratoacanthoma  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Myelodysplastic syndrome  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Non-small cell lung cancer  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Rectal adenocarcinoma  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Rectal cancer  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Renal cell carcinoma  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Schwannoma  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Squamous cell carcinoma of lung  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Superficial spreading melanoma stage unspecified  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Basosquamous Carcinoma of Skin  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Cholangiocarcinoma  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Gastric Cancer  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Skin Cancer  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Bowen's disease  1  0/241 (0.00%)  0/116 (0.00%)  1/30 (3.33%) 
Lung Neoplasm  1  0/241 (0.00%)  0/116 (0.00%)  1/30 (3.33%) 
Metastatic neoplasm  1  0/241 (0.00%)  0/116 (0.00%)  1/30 (3.33%) 
Nervous system disorders       
Cerebrovascular accident  1  3/241 (1.24%)  0/116 (0.00%)  0/30 (0.00%) 
Syncope  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Central nervous system haemorrhage  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Cerebral haemorrhage  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Haemorrhage intracranial  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Metabolic encephalopathy  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Major depression  1  0/241 (0.00%)  0/116 (0.00%)  1/30 (3.33%) 
Renal and urinary disorders       
Cystitis haemorrhagic  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Haematuria  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Renal failure  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Reproductive system and breast disorders       
Prostatic obstruction  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Testicular hypertrophy  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pleural effusion  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Pulmonary embolism  1  2/241 (0.83%)  0/116 (0.00%)  0/30 (0.00%) 
Chronic obstructive pulmonary disease  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Pneumonitis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Pulmonary oedema  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Respiratory failure  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis atopic  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Rash maculo-papular  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Surgical and medical procedures       
Fracture treatment  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  1/241 (0.41%)  1/116 (0.86%)  0/30 (0.00%) 
Aortic stenosis  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Capillary leak syndrome  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Diabetic macroangiopathy  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Dry gangrene  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Orthostatic hypotension  1  0/241 (0.00%)  1/116 (0.86%)  0/30 (0.00%) 
Peripheral artery thrombosis  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Thrombophlebitis superficial  1  1/241 (0.41%)  0/116 (0.00%)  0/30 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Obinutuzumab + Chlorambucil (GClb) Chlorambucil (Clb) Crossover Subjects: Obinutuzumab + Chlorambucil (GClb)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   215/241 (89.21%)   89/116 (76.72%)   23/30 (76.67%) 
Blood and lymphatic system disorders       
Neutropenia  1  99/241 (41.08%)  21/116 (18.10%)  12/30 (40.00%) 
Thrombocytopenia  1  36/241 (14.94%)  9/116 (7.76%)  7/30 (23.33%) 
Anaemia  1  27/241 (11.20%)  12/116 (10.34%)  3/30 (10.00%) 
Leukopenia  1  17/241 (7.05%)  0/116 (0.00%)  5/30 (16.67%) 
Gastrointestinal disorders       
Nausea  1  32/241 (13.28%)  29/116 (25.00%)  3/30 (10.00%) 
Diarrhoea  1  23/241 (9.54%)  13/116 (11.21%)  3/30 (10.00%) 
Constipation  1  17/241 (7.05%)  12/116 (10.34%)  2/30 (6.67%) 
Vomiting  1  13/241 (5.39%)  14/116 (12.07%)  0/30 (0.00%) 
General disorders       
Pyrexia  1  25/241 (10.37%)  8/116 (6.90%)  2/30 (6.67%) 
Fatigue  1  16/241 (6.64%)  12/116 (10.34%)  1/30 (3.33%) 
Asthenia  1  17/241 (7.05%)  8/116 (6.90%)  1/30 (3.33%) 
Infections and infestations       
Bronchitis  1  10/241 (4.15%)  8/116 (6.90%)  1/30 (3.33%) 
Urinary tract infection  2  14/241 (5.81%)  2/116 (1.72%)  0/30 (0.00%) 
Viral Upper Respiratory Tract Infections  2  14/241 (5.81%)  6/116 (5.17%)  0/30 (0.00%) 
Herpes Zoster  2  0/241 (0.00%)  0/116 (0.00%)  2/30 (6.67%) 
Injury, poisoning and procedural complications       
Infusion related reaction  1  147/241 (61.00%)  0/116 (0.00%)  15/30 (50.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  8/241 (3.32%)  9/116 (7.76%)  2/30 (6.67%) 
Nervous system disorders       
Headache  1  19/241 (7.88%)  8/116 (6.90%)  0/30 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  22/241 (9.13%)  8/116 (6.90%)  4/30 (13.33%) 
Dyspnoea  1  5/241 (2.07%)  8/116 (6.90%)  2/30 (6.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
2
Term from vocabulary, MedDRA 20.0
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
Name/Title: Medical Communications
Organization: Hoffman-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01010061     History of Changes
Obsolete Identifiers: NCT02035462
Other Study ID Numbers: BO21004 (Stage 1a)
2009-012476-28; CLL11
First Submitted: November 6, 2009
First Posted: November 9, 2009
Results First Submitted: December 2, 2013
Results First Posted: April 1, 2014
Last Update Posted: September 14, 2018