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A Study of Rituximab (MabThera) Subcutaneous (SC) Versus Rituximab (MabThera) Intravenous in Participannts With Follicular Non-Hodgkin's Lymphoma

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: NCT01200758
Recruitment Status : Completed
First Posted : September 14, 2010
Results First Posted : August 5, 2015
Last Update Posted : November 27, 2018
Sponsor:
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: Rituximab SC
Drug: Rituximab IV
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone/Prednisolone
Enrollment 410
Recruitment Details  
Pre-assignment Details Screening/baseline tests were performed within 28 days before randomization. Randomization was centralized in a 1:1 fashion using the Pocock and Simon dynamic randomization algorithm. The study was conducted in 2 stages: Stage I & II. All participants irrespective of the treatment period completion commenced follow-up period in both Stage I and II.
Arm/Group Title Stage I: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I: Rituximab SC + Chemotherapy (CHOP/CVP) Stage II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description Eight cycles of rituximab intravenous (IV) infusion (375 milligrams per square meter [mg/m^2]; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least partial response (PR) during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months. First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 milligrams [mg]; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months. Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months. First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Period Title: Stage I
Started 64 63 0 [1] 0 [1]
Completed 46 [2] 46 [2] 0 0
Not Completed 18 17 0 0
Reason Not Completed
Death             0             1             0             0
Physician Decision             1             1             0             0
Lack of Efficacy             2             1             0             0
Adverse Event             5             5             0             0
Withdrawal by Subject             1             2             0             0
Disease Progression             9             7             0             0
[1]
Different participants were randomized into different stages of the study.
[2]
Participants completed treatment period.
Period Title: Stage 2
Started 0 [1] 0 [1] 141 142
Completed 0 0 100 [2] 92 [2]
Not Completed 0 0 41 50
Reason Not Completed
Disease Progression             0             0             16             21
Lack of Efficacy             0             0             4             2
Physician Decision             0             0             5             7
Adverse Event             0             0             5             9
Withdrawal by Subject             0             0             4             1
Lost to Follow-up             0             0             3             1
Protocol Violation             0             0             1             4
Death             0             0             3             5
[1]
Different participants were randomized into different stages of the study.
[2]
Participants completed treatment period.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP) Total
Hide Arm/Group Description Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months. First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months. Total of all reporting groups
Overall Number of Baseline Participants 205 205 410
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Population included all participants who were randomized into study irrespective whether they received study drug or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 205 participants 205 participants 410 participants
56.9  (12.69) 56.1  (12.66) 56.5  (12.67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 205 participants 205 participants 410 participants
Female
99
  48.3%
120
  58.5%
219
  53.4%
Male
106
  51.7%
85
  41.5%
191
  46.6%
1.Primary Outcome
Title Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab
Hide Description [Not Specified]
Time Frame Stage I: Cycle (Cy) 7 Day (D) 21 (within 2 hours predose on Cy8) of induction treatment (1 Cy=3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Stage I pharmacokinetic (PK) evaluable population comprised all participants with data for Ctrough available at Cycle 7 and/or observed area under the serum concentration-time curve (AUC) available at Cycle 7. Participants were analyzed as per treatment received. Number of participants analyzed = participants analyzed for this outcome measure.
Arm/Group Title Stage I: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 48 54
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms per milliliter (mcg/mL)
83.1
(36.7%)
134.6
(43.2%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferior Ctrough in SC formulation was demonstrated, if the lower bound of 90% confidence interval (CI) was above 0.8.
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.62
Confidence Interval (2-Sided) 90%
1.36 to 1.94
Estimation Comments Geometric mean ratio adjusted for tumor load at baseline.
2.Primary Outcome
Title Stage II: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for Non-Hodgkin Lymphoma (NHL)
Hide Description Overall Response comprised complete response (CR), CR unconfirmed (CRu), or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and computed tomography (CT) scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by more than (>) 75% in the sum of the products of greatest diameters (SPD); PR: Greater than or equal to (≥) 50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.
Time Frame Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Stage II ITT Population included all participants who were randomized in Stage II irrespective whether they received study drug or not.
Arm/Group Title Stage II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 141 142
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
85.1
(78.1 to 90.5)
80.3
(72.8 to 86.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2835
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value -4.82
Confidence Interval (2-Sided) 95%
-14.0 to 4.4
Estimation Comments The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.38 to 1.33
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Stage I: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Hide Description Overall Response comprised CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in the SPD; PR: ≥50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.
Time Frame Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Stage I ITT Population included all participants who were randomized in Stage I irrespective whether they received study drug or not.
Arm/Group Title Stage I: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 64 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
82.8
(71.3 to 91.1)
90.5
(80.4 to 96.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2047
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 7.66
Confidence Interval (2-Sided) 95%
-5.0 to 20.3
Estimation Comments The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.97
Confidence Interval (2-Sided) 95%
0.68 to 5.71
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Hide Description Overall Response comprised of CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumour response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD; PR: ≥50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 205 205
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
84.9
(79.2 to 89.5)
84.4
(78.7 to 89.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8911
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value -0.49
Confidence Interval (2-Sided) 95%
-7.7 to 6.8
Estimation Comments The 95% CI for the difference in response rates was estimated using the Hauck-Anderson.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.56 to 1.65
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Stage I: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Hide Description Complete Response was comprised CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Stage I ITT Population.
Arm/Group Title Stage I: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 64 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
25.0
(15.0 to 37.4)
42.9
(30.5 to 56.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0335
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in CRR
Estimated Value 17.86
Confidence Interval (2-Sided) 95%
0.8 to 35.0
Estimation Comments The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
1.06 to 4.78
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Stage II: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Hide Description Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Stage II ITT Population.
Arm/Group Title Stage II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 141 142
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
34.8
(26.9 to 43.2)
28.2
(20.9 to 36.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2331
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value -6.58
Confidence Interval (2-Sided) 95%
-17.8 to 4.6
Estimation Comments The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.44 to 1.22
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Hide Description Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 205 205
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
31.7
(25.4 to 38.6)
32.2
(25.9 to 39.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9157
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
-8.8 to 9.8
Estimation Comments The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.66 to 1.51
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL
Hide Description Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; only participants who entered the maintenance phase and received at least 1 cycle of rituximab maintenance treatment from Cycle 9 to Cycle 20 were included in the analysis.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 178 172
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
57.9
(50.3 to 65.2)
50.6
(42.9 to 58.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1715
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value -7.28
Confidence Interval (2-Sided) 95%
-18.0 to 3.5
Estimation Comments The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.52 to 1.22
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL
Hide Description Overall Response comprised of CR, CRu, or PR . A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks)
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Hide Analysis Population Description
ITT population; only participants who entered the maintenance phase and received at least 1 cycle of rituximab maintenance treatment from Cycle 9 to Cycle 20 were included in the analysis.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 178 172
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
78.1
(71.3 to 83.9)
77.9
(71.0 to 83.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9671
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-9.2 to 8.8
Estimation Comments The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.60 to 1.64
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse or Death
Hide Description Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Time Frame Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 205 205
Measure Type: Number
Unit of Measure: percentage of participants
34.6 31.7
11.Secondary Outcome
Title Stage I and II (Pooled): Progression-Free Survival (PFS) Assessed Using International Working Group Response Criteria for NHL
Hide Description PFS was defined as the time from randomization to disease progression/relapse or death due to any cause. If the specified event (disease progression/relapse, death) did not occur, PFS was censored at the last tumor assessment date showing no disease progression, either during treatment or follow-up. Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. PFS analysis was performed using Kaplan - Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Time Frame Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 205 205
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
Data for upper limit of 95% CI were not reached due to low number (<50%) of participants with event of interest.
[2]
Data for median and corresponding 95% CI were not reached due to low number (<50%) of participants with event of interest.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5526
Comments [Not Specified]
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.64 to 1.26
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse, New Anti-Lymphoma Treatment or Death Assessed Using International Working Group Response Criteria for NHL
Hide Description Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Time Frame Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 205 205
Measure Type: Number
Unit of Measure: percentage of participants
36.1 35.1
13.Secondary Outcome
Title Stage I and II (Pooled): Event-Free Survival Assessed Using International Working Group Response Criteria for NHL
Hide Description Event-free survival was defined as the time from randomization to disease progression/relapse, death or initiation of new NHL therapy. If the specified event (progression/relapse, death or new anti-lymphoma treatment) did not occur, event-free survival was censored at the last tumor assessment date either during treatment or follow up. Event-free survival analysis was performed using Kaplan-Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Time Frame Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 205 205
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(2126 to NA)
NA [2] 
(NA to NA)
[1]
Data for upper limit of 95% CI was not reached due to low number (<50%) of participants with event of interest.
[2]
Data for median and upper limit of 95% CI were not reached due to low number (<50%) of participants with event of interest.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9115
Comments [Not Specified]
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.71 to 1.36
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Participants Who Died
Hide Description [Not Specified]
Time Frame Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 205 205
Measure Type: Number
Unit of Measure: percentage of participants
12.7 8.8
15.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause. Participants without event were censored at the time of last follow-up information for survival, ie, at the last time known to be alive.
Time Frame Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 205 205
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Data for median and corresponding 95% CI were not reached due to low number (<10%) of participants with event of interest.
16.Secondary Outcome
Title Stage I: Observed Area Under the Serum Concentration-Time Curve (AUC) of Rituximab
Hide Description AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Predose (within 2 hr) and 24 hrs postdose on Cy 7 (D1,3,7,15), predose (0 hr) on Cy 8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy 7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])
Time Frame Stage I (Induction): Predose (within 2 hour [hr]) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
Stage I PK evaluable population. Here, number of participants analyzed = participants evaluable for this outcome measure.
Arm/Group Title Stage I: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 58 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg*day/mL
2734.21
(32.51%)
3778.93
(37.59%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments The ratio of observed rituximab serum was determined as AUC SC/AUC IV during Cycle 7 of induction treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.38
Confidence Interval (2-Sided) 90%
1.24 to 1.53
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Stage I: Maximum Serum Concentrations (Cmax) of IV and SC Rituximab
Hide Description Predose (within 2 hr) and 24 hrs postdose on Cy7 (D1,3,7,15), predose (0 hr) on Cy8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])
Time Frame Stage I (Induction): Predose (within 2hr) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 1 PK Evaluable Population. Here, number of participants analyzed = participants evaluable for this outcome measure.
Arm/Group Title Stage I: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 58 59
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
250.63
(19.66%)
236.82
(31.45%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.941
Confidence Interval (2-Sided) 95%
0.872 to 1.015
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Stage I and II (Pooled): Ctrough of Rituximab at Each Induction Treatment Cycle
Hide Description Stage I and II (Induction): Rituximab IV: Predose (within 2 hr) on D1 of Cy1-8 (1 Cy=3 weeks & 4 weeks for Cy8); Rituximab SC: Predose (within 2 hr) on D1 of Cy1 & Cy3-8 (1 Cy=3 weeks and 4 weeks for Cy8), predose (within 2 hr) on D0 of Cy2 (up to data cutoff of 31 Oct 2013 [up to 32 months])
Time Frame Stage I and II (Pooled): Predose (within 2hr) up to data cutoff of 31 Oct 2013 [up to 32 months]) (See detailed timeframe in Outcome Measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 198 193
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
Cycle 1 (n = 198, 193)
14.00
(157.53%)
12.88
(189.70%)
Cycle 2 (n = 197, 190)
30.13
(145.36%)
40.00
(124.50%)
Cycle 3 (n = 192, 190)
45.25
(110.35%)
63.83
(101.83%)
Cycle 4 (n = 186, 185)
54.06
(108.90%)
81.71
(92.28%)
Cycle 5 (n = 185, 185)
64.68
(89.90%)
98.00
(71.91%)
Cycle 6 (n = 187, 180)
71.02
(87.60%)
109.56
(58.74%)
Cycle 7 (n = 183, 172)
78.31
(77.76%)
120.75
(55.60%)
Cycle 8 (n = 52, 54)
77.60
(70.53%)
131.48
(50.20%)
19.Secondary Outcome
Title Stage I and II (Pooled): Ctrough of Rituximab at Each Maintenance Treatment Cycle
Hide Description Stage I and II (maintenance): D29 of Cy8 (induction; 1 Cy=4 weeks), predose (within 2 hr) on D1 of Cy9 to 19 (maintenance Cy1 to 12 [1 Cy=8 weeks]; up to data cutoff of 11 Jan 2016 [up to 6 years])
Time Frame Stage I and II (maintenance): Predose (within 2hr) up to data cutoff of 11 Jan 2016 [up to 6 years]) (See detailed timeframe in Outcome Measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 174 170
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
Cycle 8 (n = 174, 170)
37.69
(94.30%)
61.31
(65.52%)
Cycle 9 (n = 171, 168)
30.35
(75.03%)
49.47
(81.23%)
Cycle 10 (n = 164, 160)
28.44
(84.64%)
47.27
(73.03%)
Cycle 11 (n = 164, 157)
28.77
(65.28%)
46.70
(66.80%)
Cycle 12 (n = 160, 150)
28.80
(56.97%)
44.72
(68.74%)
Cycle 13 (n = 157, 150)
28.84
(54.04%)
44.32
(67.67%)
Cycle 14 (n = 153, 147)
28.09
(55.61%)
43.32
(67.97%)
Cycle 15 (n = 148, 143)
28.19
(52.69%)
44.11
(67.92%)
Cycle 16 (n = 150, 145)
28.05
(57.19%)
42.96
(64.32%)
Cycle 17 (n = 149, 143)
28.24
(57.51%)
42.82
(65.67%)
Cycle 18 (n = 143, 132)
28.59
(62.06%)
44.79
(68.56%)
Cycle 19 (n = 138, 131)
27.75
(78.26%)
43.69
(69.02%)
20.Secondary Outcome
Title Stage I and II (Pooled): Rituximab Levels 12 Weeks, 24 Weeks, and 36 Weeks After the Last Rituximab Administration
Hide Description [Not Specified]
Time Frame 12 weeks, 24 weeks, and 36 weeks after the last rituximab administration (up to data cutoff of 11 Jan 2016 [up to 6 years])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Population included all participants who received at least one dose of rituximab, either IV or SC. Participants were analyzed as treated. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 117 118
Median (Full Range)
Unit of Measure: mcg/mL
Week 12: Follow-up Visit 1 (n = 117, 118)
15.60
(0.70 to 80.40)
22.35
(0.65 to 107.00)
Week 24: Follow-up Visit 2 (n = 88, 96)
2.89
(0.58 to 17.40)
5.19
(0.69 to 62.10)
Week 36: Follow-up Visit 3 (n = 38, 53)
1.08
(0.52 to 51.40)
2.02
(0.53 to 33.90)
21.Secondary Outcome
Title Percentage of Participants With B-Cell Depletion by Cycle for Induction Phase
Hide Description Depletion is defined as a cluster of differentiation (CD) 19 value <80 cells per cubic millimeter (cells/mm^3).
Time Frame Stage I and II (induction): for rituximab IV - D1 of Cy 1 to 8 (1 Cy=3 weeks); for rituximab SC - D1 of Cy 1 and Cy 3 to 8, D0 of Cy 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 188 180
Measure Type: Number
Unit of Measure: percentage of participants
Cycle 1 Day 1 - Baseline (n=188, 168) 51.6 54.8
Cycle 2 Day 0 (n=183, 180) 95.1 95.0
Cycle 3 Day 1 (n=175, 175) 99.4 99.4
Cycle 4 Day 1 (n=178, 180) 99.4 100.0
Cycle 5 Day 1 (n=179, 176) 100.0 100.0
Cycle 6 Day 1 (n=173, 175) 100.0 100.0
Cycle 7 Day 1 (n=178, 173) 100.0 100.0
Cycle 8 Day 1 (n=175, 174) 100.0 100.0
22.Secondary Outcome
Title Percentage of Participants With B-Cell Depletion by Cycle for Maintenance Phase
Hide Description Depletion is defined as a CD19 value <80 cells/mm^3.
Time Frame Stage I and II (maintenance): D1 of Cy 9 to 20 (1 Cy=8 weeks) (up to data cutoff of 11 Jan 2016 [up to 6 years])
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ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
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Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 170 164
Measure Type: Number
Unit of Measure: percentage of participants
Cycle 9 Day 1 (n=170, 161) 99.4 100.0
Cycle 10 Day 1 (n=165, 164) 99.4 100.0
Cycle 11 Day 1 (n=158, 158) 99.4 100.0
Cycle 12 Day 1 (n=151, 146) 100.0 100.0
Cycle 13 Day 1 (n=149, 143) 100.0 100.0
Cycle 14 Day 1 (n=152, 143) 100.0 100.0
Cycle 15 Day 1 (n=149, 140) 100.0 100.0
Cycle 16 Day 1 (n=142, 141) 100.0 100.0
Cycle 17 Day 1 (n=145, 142) 100.0 100.0
Cycle 18 Day 1 (n=141, 140) 100.0 100.0
Cycle 19 Day 1 (n=140, 138) 100.0 100.0
Cycle 20 Day 1 (n=139, 134) 100.0 100.0
23.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Hide Description Levels of HACA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])
Time Frame Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description)
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Safety Analysis Population: included 6 participants who were randomized under Rituximab SC arm but withdrew after Cy1 and then analyzed under Rituximab IV arm. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
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Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 208 197
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (n=208, 191) 5.8 2.6
Post-Baseline (n=206, 197) 1.5 2.0
24.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Human Antibodies (HAHAs) to Rituximab
Hide Description Levels of HAHA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])
Time Frame Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description)
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Hide Analysis Population Description
Safety Analysis Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description:
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 68 197
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (n=68, 188) 10.3 11.2
Post-Baseline (n=66, 197) 7.6 13.2
25.Secondary Outcome
Title Stage I and II (Pooled): Percentage of Responses Showing Time Saved of Staff as Per Physician/Nurse Opinions With Each Administration of Rituximab SC as Compared to Rituximab IV at the End of Cy 8, 15 and 20
Hide Description All investigator physicians and nurses involved in this study were asked to provide the staff time that could be saved with each administration of rituximab SC as compared with rituximab IV to participants in routine practice afetr Cy 8, 15, 20 and categorized as less than (<) 1 hr, at least 1 hr but <2 hrs, at least 2 hrs but <3 hrs, at least 3 hrs but <4 hrs, >/=4 hrs. Staff were asked not to consider the time needed for the first IV administration. Analysis was done in all participants to show a comparison on the time saved by staffs when administered via SC and IV.
Time Frame After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20)
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ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title All Participants
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Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP): First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months. Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP): Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 166
Measure Type: Number
Unit of Measure: percentage of responses
After Cy8: <1 hour (n=166) 11
After Cy8: ≥1 to <2 hours (n=166) 20
After Cy8: ≥2 to <3 hours (n=166) 35
After Cy8: ≥3 to <4 hours (n=166) 18
After Cy8: ≥4 hours (n=166) 16
After Cy15: <1 hour (n=130) 13
After Cy15: ≥1 to <2 hours (n=130) 17
After Cy15: ≥2 to <3 hours (n=126) 34
After Cy15: ≥3 to <4 hours (n=130) 14
After Cy15: ≥4 hours (n=130) 22
After Cy20: <1 hour (n=126) 14
After Cy20: ≥1 to <2 hours (n=126) 32
After Cy20: ≥2 to <3 hours (n=126) 21
After Cy20: ≥3 to <4 hours (n=126) 13
After Cy20: ≥4 hours (n=126) 19
26.Secondary Outcome
Title Percentage of Responses Who Showed Rituximab SC Formulation Convenient as Compared to Rituximab IV Formulation as Assessed by Physician/Nurse Opinion
Hide Description All investigator physicians and nurses involved in this study were asked to complete question i.e. "Which formulation of rituximab (SC or IV) do you think is more convenient?" based on their experience with the rituximab SC and IV formulations across all participants and presented as rituximab SC is much more convenient; rituximab SC is a little more convenient; both formulations are equally convenient; rituximab IV is a little more convenient; and rituximab IV is much more convenient.
Time Frame After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20)
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ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title All Participants
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Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP): First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months. Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP): Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
Overall Number of Participants Analyzed 166
Measure Type: Number
Unit of Measure: percentage of responses
Cy8: Rituximab SC much more convenient (n=166) 81
Cy8: Rituximab SC little more convenient (n=166) 13
Cy8: Both formulations equally convenient (n=166) 2
Cy8: Rituximab IV little more convenient (n=166) 4
Cy8: Rituximab IV much more convenient (n=166) 0
Cy15: Rituximab SC much more convenient (n=130) 88
Cy15: Rituximab SC little more convenient (n=130) 7
Cy15: Both formulations equally convenient (n=130) 5
Cy15: Rituximab IV little more convenient (n=130) 0
Cy15: Rituximab IV much more convenient (n=130) 0
Cy20: Rituximab SC much more convenient (n=126) 88
Cy20: Rituximab SC little more convenient (n=126) 9
Cy20: Both formulations equally convenient (n=126) 2
Cy20: Rituximab IV little more convenient (n=126) 1
Cy20: Rituximab IV much more convenient (n=126) 0
Time Frame Baseline up to data cutoff date of 31 Oct 2017 (up to 6 years)
Adverse Event Reporting Description Safety Analysis Population included all participants who received at least one dose of rituximab, either IV or SC. Safety Analysis Population included 6 participants who were randomized under Rituximab SC arm but withdrew after Cy1 and then analyzed under Rituximab IV arm.
 
Arm/Group Title Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Hide Arm/Group Description Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months. First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
All-Cause Mortality
Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Affected / at Risk (%) Affected / at Risk (%)
Total   76/210 (36.19%)   74/197 (37.56%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  10/210 (4.76%)  12/197 (6.09%) 
Neutropenia * 1  4/210 (1.90%)  6/197 (3.05%) 
Anaemia * 1  1/210 (0.48%)  2/197 (1.02%) 
Thrombocytopenia * 1  1/210 (0.48%)  0/197 (0.00%) 
Cardiac disorders     
Acute coronary syndrome * 1  1/210 (0.48%)  0/197 (0.00%) 
Atrial fibrillation * 1  0/210 (0.00%)  2/197 (1.02%) 
Myocardial infarction * 1  1/210 (0.48%)  1/197 (0.51%) 
Acute myocardial infarction * 1  0/210 (0.00%)  1/197 (0.51%) 
Cardiac arrest * 1  1/210 (0.48%)  0/197 (0.00%) 
Cardiac failure congestive * 1  1/210 (0.48%)  1/197 (0.51%) 
Myocardial ischaemia * 1  1/210 (0.48%)  0/197 (0.00%) 
Bradycardia * 2  1/210 (0.48%)  0/197 (0.00%) 
Ear and labyrinth disorders     
Vertigo * 2  1/210 (0.48%)  2/197 (1.02%) 
Gastrointestinal disorders     
Abdominal pain * 1  2/210 (0.95%)  2/197 (1.02%) 
Constipation * 1  3/210 (1.43%)  0/197 (0.00%) 
Ascites * 1  1/210 (0.48%)  0/197 (0.00%) 
Oral lichen planus * 1  1/210 (0.48%)  0/197 (0.00%) 
Pancreatitis * 1  1/210 (0.48%)  0/197 (0.00%) 
Colitis ulcerative * 1  0/210 (0.00%)  1/197 (0.51%) 
Diarrhoea * 1  0/210 (0.00%)  1/197 (0.51%) 
Duodenal ulcer * 1  1/210 (0.48%)  0/197 (0.00%) 
Enteritis * 1  1/210 (0.48%)  0/197 (0.00%) 
Ileus paralytic * 1  0/210 (0.00%)  1/197 (0.51%) 
Mouth ulceration * 1  0/210 (0.00%)  1/197 (0.51%) 
Proctalgia * 1  1/210 (0.48%)  0/197 (0.00%) 
Vomiting * 1  0/210 (0.00%)  1/197 (0.51%) 
Mesenteric vein thrombosis * 2  1/210 (0.48%)  0/197 (0.00%) 
Abdominal wall haematoma * 2  1/210 (0.48%)  0/197 (0.00%) 
Colitis * 2  0/210 (0.00%)  1/197 (0.51%) 
Large intestine polyp * 2  1/210 (0.48%)  0/197 (0.00%) 
General disorders     
Pyrexia * 1  5/210 (2.38%)  6/197 (3.05%) 
Malaise * 1  1/210 (0.48%)  0/197 (0.00%) 
Multi-organ failure * 1  1/210 (0.48%)  0/197 (0.00%) 
Death * 2  2/210 (0.95%)  0/197 (0.00%) 
Hepatobiliary disorders     
Cholangitis * 1  0/210 (0.00%)  1/197 (0.51%) 
Cholecystitis acute * 1  1/210 (0.48%)  0/197 (0.00%) 
Jaundice * 2  0/210 (0.00%)  1/197 (0.51%) 
Infections and infestations     
Pneumonia * 1  7/210 (3.33%)  11/197 (5.58%) 
Neutropenic sepsis * 1  4/210 (1.90%)  1/197 (0.51%) 
Cystitis * 1  1/210 (0.48%)  2/197 (1.02%) 
Lower respiratory tract infection * 1  2/210 (0.95%)  2/197 (1.02%) 
Urinary tract infection * 1  1/210 (0.48%)  2/197 (1.02%) 
Bronchitis * 1  2/210 (0.95%)  1/197 (0.51%) 
Infection * 1  2/210 (0.95%)  0/197 (0.00%) 
Sepsis * 1  1/210 (0.48%)  3/197 (1.52%) 
Bacterial prostatitis * 1  0/210 (0.00%)  1/197 (0.51%) 
Creutzfeldt-Jakob disease * 1  0/210 (0.00%)  1/197 (0.51%) 
Empyema * 1  0/210 (0.00%)  1/197 (0.51%) 
Gastroenteritis norovirus * 1  1/210 (0.48%)  0/197 (0.00%) 
Giardiasis * 1  0/210 (0.00%)  1/197 (0.51%) 
Meningitis * 1  0/210 (0.00%)  2/197 (1.02%) 
Otitis externa * 1  1/210 (0.48%)  0/197 (0.00%) 
Pneumocystis jirovecii pneumonia * 1  1/210 (0.48%)  0/197 (0.00%) 
Pneumonia mycoplasmal * 1  0/210 (0.00%)  1/197 (0.51%) 
Postoperative wound infection * 1  0/210 (0.00%)  1/197 (0.51%) 
Respiratory tract infection * 1  1/210 (0.48%)  1/197 (0.51%) 
Upper respiratory tract infection * 1  0/210 (0.00%)  1/197 (0.51%) 
Urinary tract infection bacterial * 1  0/210 (0.00%)  1/197 (0.51%) 
Appendicitis * 2  1/210 (0.48%)  1/197 (0.51%) 
Cellulitis * 2  1/210 (0.48%)  1/197 (0.51%) 
Urosepsis * 2  0/210 (0.00%)  2/197 (1.02%) 
Abscess * 2  1/210 (0.48%)  0/197 (0.00%) 
Bacteraemia * 2  0/210 (0.00%)  1/197 (0.51%) 
Chronic hepatitis B * 2  0/210 (0.00%)  1/197 (0.51%) 
Erysipelas * 2  0/210 (0.00%)  1/197 (0.51%) 
Hepatitis viral * 2  0/210 (0.00%)  1/197 (0.51%) 
Intestinal sepsis * 2  1/210 (0.48%)  0/197 (0.00%) 
Pulmonary tuberculosis * 2  1/210 (0.48%)  0/197 (0.00%) 
Pyelonephritis * 2  1/210 (0.48%)  0/197 (0.00%) 
Respiratory tract infection fungal * 2  1/210 (0.48%)  0/197 (0.00%) 
Cellulitis gangrenous * 2  1/210 (0.48%)  0/197 (0.00%) 
Injury, poisoning and procedural complications     
Stress fracture * 1  1/210 (0.48%)  0/197 (0.00%) 
Ankle fracture * 2  1/210 (0.48%)  0/197 (0.00%) 
Femoral neck fracture * 2  1/210 (0.48%)  0/197 (0.00%) 
Foreign body * 1  1/210 (0.48%)  0/197 (0.00%) 
Multiple injuries * 1  1/210 (0.48%)  0/197 (0.00%) 
Skull fracture * 2  0/210 (0.00%)  1/197 (0.51%) 
Fall * 2  0/210 (0.00%)  1/197 (0.51%) 
Lumbar vertebral fracture * 2  0/210 (0.00%)  1/197 (0.51%) 
Procedural pain * 2  0/210 (0.00%)  1/197 (0.51%) 
Traumatic intracranial haemorrhage * 2  1/210 (0.48%)  0/197 (0.00%) 
Wrist fracture * 2  0/210 (0.00%)  1/197 (0.51%) 
Investigations     
Eastern Cooperative Oncology Group performance status worsened * 1  1/210 (0.48%)  0/197 (0.00%) 
International normalised ratio increased * 2  0/210 (0.00%)  1/197 (0.51%) 
Metabolism and nutrition disorders     
Hyponatraemia * 2  0/210 (0.00%)  2/197 (1.02%) 
Tumour lysis syndrome * 2  0/210 (0.00%)  1/197 (0.51%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/210 (0.48%)  2/197 (1.02%) 
Osteoarthritis * 1  2/210 (0.95%)  0/197 (0.00%) 
Arthralgia * 1  0/210 (0.00%)  2/197 (1.02%) 
Flank pain * 1  0/210 (0.00%)  1/197 (0.51%) 
Pain in extremity * 1  1/210 (0.48%)  0/197 (0.00%) 
Pathological fracture * 1  0/210 (0.00%)  1/197 (0.51%) 
Arthritis * 2  0/210 (0.00%)  1/197 (0.51%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma * 1  1/210 (0.48%)  0/197 (0.00%) 
Prostate cancer * 2  1/210 (0.48%)  1/197 (0.51%) 
Rectal adenocarcinoma * 2  1/210 (0.48%)  0/197 (0.00%) 
Squamous cell carcinoma of lung * 1  1/210 (0.48%)  0/197 (0.00%) 
Squamous cell carcinoma of skin * 1  1/210 (0.48%)  1/197 (0.51%) 
Thyroid cancer * 1  1/210 (0.48%)  0/197 (0.00%) 
Adenocarcinoma of colon * 2  0/210 (0.00%)  1/197 (0.51%) 
Cervix Carcinoma Stage 0 * 2  0/210 (0.00%)  1/197 (0.51%) 
Colon cancer * 2  1/210 (0.48%)  1/197 (0.51%) 
Kaposi's sarcoma * 2  0/210 (0.00%)  1/197 (0.51%) 
Lung neoplasm malignant * 2  1/210 (0.48%)  0/197 (0.00%) 
Myelodysplastic syndrome * 2  1/210 (0.48%)  0/197 (0.00%) 
Renal cell carcinoma * 2  0/210 (0.00%)  1/197 (0.51%) 
Uterine leiomyoma * 2  0/210 (0.00%)  1/197 (0.51%) 
Adenocarcinoma * 2  1/210 (0.48%)  0/197 (0.00%) 
Breast cancer * 2  0/210 (0.00%)  1/197 (0.51%) 
Plasma cell myeloma * 2  0/210 (0.00%)  1/197 (0.51%) 
Squamous cell carcinoma * 2  0/210 (0.00%)  1/197 (0.51%) 
Nervous system disorders     
Coma hepatic * 1  1/210 (0.48%)  0/197 (0.00%) 
Hydrocephalus * 1  0/210 (0.00%)  1/197 (0.51%) 
Migraine * 1  1/210 (0.48%)  0/197 (0.00%) 
Paraesthesia * 1  0/210 (0.00%)  1/197 (0.51%) 
Sciatica * 1  1/210 (0.48%)  0/197 (0.00%) 
Cognitive disorder * 2  2/210 (0.95%)  0/197 (0.00%) 
Hypoglycaemic coma * 2  1/210 (0.48%)  0/197 (0.00%) 
Transient ischaemic attack * 2  1/210 (0.48%)  0/197 (0.00%) 
Psychiatric disorders     
Major depression * 2  1/210 (0.48%)  0/197 (0.00%) 
Bipolar disorder * 2  1/210 (0.48%)  0/197 (0.00%) 
Renal and urinary disorders     
Hydronephrosis * 1  0/210 (0.00%)  2/197 (1.02%) 
Urinary retention * 2  1/210 (0.48%)  0/197 (0.00%) 
Calculus bladder * 2  1/210 (0.48%)  0/197 (0.00%) 
Reproductive system and breast disorders     
Pelvic cyst * 2  0/210 (0.00%)  1/197 (0.51%) 
Ovarian cyst * 2  0/210 (0.00%)  1/197 (0.51%) 
Uterovaginal prolapse * 2  0/210 (0.00%)  1/197 (0.51%) 
Uterine polyp * 2  0/210 (0.00%)  1/197 (0.51%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  3/210 (1.43%)  2/197 (1.02%) 
Pulmonary embolism * 1  4/210 (1.90%)  1/197 (0.51%) 
Pleural effusion * 1  1/210 (0.48%)  1/197 (0.51%) 
Acute respiratory failure * 1  1/210 (0.48%)  1/197 (0.51%) 
Pneumothorax * 1  1/210 (0.48%)  0/197 (0.00%) 
Bronchitis chronic * 2  1/210 (0.48%)  0/197 (0.00%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis * 1  1/210 (0.48%)  0/197 (0.00%) 
Lichen planus * 1  1/210 (0.48%)  0/197 (0.00%) 
Rash * 1  1/210 (0.48%)  0/197 (0.00%) 
Skin ulcer * 1  1/210 (0.48%)  0/197 (0.00%) 
Surgical and medical procedures     
Bladder calculus removal * 2  1/210 (0.48%)  0/197 (0.00%) 
Hysterectomy * 2  0/210 (0.00%)  1/197 (0.51%) 
Vascular disorders     
Arterial occlusive disease * 1  0/210 (0.00%)  1/197 (0.51%) 
Deep vein thrombosis * 2  1/210 (0.48%)  0/197 (0.00%) 
Hypertensive crisis * 2  1/210 (0.48%)  1/197 (0.51%) 
Vena cava thrombosis * 1  0/210 (0.00%)  1/197 (0.51%) 
Subclavian artery occlusion * 2  0/210 (0.00%)  1/197 (0.51%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.1)
2
Term from vocabulary, MedDRA (18.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Affected / at Risk (%) Affected / at Risk (%)
Total   187/210 (89.05%)   186/197 (94.42%) 
Blood and lymphatic system disorders     
Neutropenia * 2  57/210 (27.14%)  65/197 (32.99%) 
Anaemia * 2  26/210 (12.38%)  30/197 (15.23%) 
Leukopenia * 2  23/210 (10.95%)  13/197 (6.60%) 
Gastrointestinal disorders     
Nausea * 1  47/210 (22.38%)  65/197 (32.99%) 
Constipation * 1  55/210 (26.19%)  50/197 (25.38%) 
Diarrhoea * 2  35/210 (16.67%)  34/197 (17.26%) 
Vomiting * 2  27/210 (12.86%)  29/197 (14.72%) 
Abdominal pain * 2  25/210 (11.90%)  29/197 (14.72%) 
Dyspepsia * 2  14/210 (6.67%)  16/197 (8.12%) 
Abdominal pain upper * 2  11/210 (5.24%)  11/197 (5.58%) 
Stomatitis * 2  11/210 (5.24%)  12/197 (6.09%) 
General disorders     
Injection site erythema * 1  0/210 (0.00%)  27/197 (13.71%) 
Fatigue * 2  38/210 (18.10%)  42/197 (21.32%) 
Asthenia * 2  27/210 (12.86%)  35/197 (17.77%) 
Pyrexia * 2  29/210 (13.81%)  29/197 (14.72%) 
Chills * 2  18/210 (8.57%)  16/197 (8.12%) 
Mucosal inflammation * 2  12/210 (5.71%)  9/197 (4.57%) 
Chest pain * 1  7/210 (3.33%)  14/197 (7.11%) 
Injection site pain * 2  0/210 (0.00%)  16/197 (8.12%) 
Oedema peripheral * 2  13/210 (6.19%)  10/197 (5.08%) 
Influenza like illness * 2  12/210 (5.71%)  5/197 (2.54%) 
Infections and infestations     
Upper respiratory tract infection * 1  26/210 (12.38%)  30/197 (15.23%) 
Urinary tract infection * 1  28/210 (13.33%)  16/197 (8.12%) 
Nasopharyngitis * 1  25/210 (11.90%)  22/197 (11.17%) 
Bronchitis * 1  15/210 (7.14%)  15/197 (7.61%) 
Sinusitis * 1  10/210 (4.76%)  14/197 (7.11%) 
Conjunctivitis * 2  12/210 (5.71%)  9/197 (4.57%) 
Influenza * 2  14/210 (6.67%)  9/197 (4.57%) 
Pneumonia * 2  4/210 (1.90%)  12/197 (6.09%) 
Musculoskeletal and connective tissue disorders     
Bone pain * 2  16/210 (7.62%)  20/197 (10.15%) 
Back pain * 2  25/210 (11.90%)  18/197 (9.14%) 
Myalgia * 2  10/210 (4.76%)  16/197 (8.12%) 
Arthralgia * 2  22/210 (10.48%)  26/197 (13.20%) 
Pain in extremity * 2  11/210 (5.24%)  22/197 (11.17%) 
Muscle spasms * 2  7/210 (3.33%)  17/197 (8.63%) 
Nervous system disorders     
Paraesthesia * 2  27/210 (12.86%)  30/197 (15.23%) 
Neuropathy peripheral * 2  30/210 (14.29%)  24/197 (12.18%) 
Dizziness * 2  15/210 (7.14%)  16/197 (8.12%) 
Headache * 1  20/210 (9.52%)  27/197 (13.71%) 
Hypoaesthesia * 2  7/210 (3.33%)  10/197 (5.08%) 
Psychiatric disorders     
Insomnia * 1  19/210 (9.05%)  19/197 (9.64%) 
Anxiety * 2  7/210 (3.33%)  11/197 (5.58%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  32/210 (15.24%)  49/197 (24.87%) 
Oropharyngeal pain * 1  16/210 (7.62%)  16/197 (8.12%) 
Dyspnoea * 1  13/210 (6.19%)  21/197 (10.66%) 
Skin and subcutaneous tissue disorders     
Alopecia * 2  23/210 (10.95%)  28/197 (14.21%) 
Erythema * 2  11/210 (5.24%)  19/197 (9.64%) 
Pruritus * 2  25/210 (11.90%)  20/197 (10.15%) 
Rash * 2  14/210 (6.67%)  20/197 (10.15%) 
Vascular disorders     
Hypertension * 2  13/210 (6.19%)  12/197 (6.09%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.1)
2
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: global-roche-genentech-trials@gene.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01200758    
Other Study ID Numbers: BO22334
2010-021377-36
First Submitted: September 10, 2010
First Posted: September 14, 2010
Results First Submitted: July 7, 2015
Results First Posted: August 5, 2015
Last Update Posted: November 27, 2018