A Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+Obinutuzumab (GA101) in Participants With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma (GADOLIN)
Study Details
Study Description
Brief Summary
This open-label, multicenter, randomized Phase III study will investigate the efficacy, safety, pharmacokinetics and pharmacoeconomics of obinutuzumab (RO5072759, GA101) combined with bendamustine followed by continued obinutuzumab treatment (maintenance monotherapy) compared with bendamustine alone treatment in participants with rituximab-refractory indolent Non-Hodgkin's lymphoma (iNHL). The end of study was defined to when safety follow-up for all patients had been completed (2 years' safety follow-up from last dose).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Bendamustine Alone Participants will receive bendamustine 120 milligrams per meter square (mg/m^2) Intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. |
Drug: Bendamustine
IV infusion.
|
| Experimental: Obinutuzumab + Bendamustine Induction phase: Participants will receive bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants will also receive obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with complete response (CR), partial response (PR) or stable response (SD) then will receive obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurs first). |
Drug: Obinutuzumab
IV infusion.
Other Names:
Drug: Bendamustine
IV infusion.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death [Baseline until PD or death, whichever occurred first (assessed at baseline, 14 days prior to Cycle [Cy] 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1, then every 3 months up to 2 years and every 6 months for next 2 years [up to 4.5 years overall])]
PD was assessed by an IRC according to the modified response criteria for indolent Non-Hodgkin's Lymphoma (iNHL) (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50 percent (%) increase from nadir in the sum of product diameter (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions (example: splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of less than (<) 1.0 cm must increase by greater than or equal to (≥) 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node greater than (>) 1 cm in its short axis.
- Progression-Free Survival (PFS) as Assessed by IRC [Baseline until PD or death, whichever occurred first (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1, then every 3 months up to 2 years and every 6 months for next 2 years [up to 4.5 years overall])]
PFS was defined as the time from randomization to the first occurrence of PD or death as assessed by an IRC according to the modified response criteria for iNHL (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be PD, a lymph node with a diameter of the short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis. PFS was estimated using Kaplan-Meier method and 95% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.
Secondary Outcome Measures
- Number of Participants With PD or Death as Assessed by Investigator [Baseline until PD or death, whichever occurred first (up to 8.5 years overall))]
PD was assessed by an investigator according to the modified response criteria for iNHL (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis.
- PFS as Assessed by Investigator [Baseline until PD or death, whichever occurred first (up to 8.5 years overall)]
PFS was defined as the time from randomization to the first occurrence of PD as assessed by an investigator according to the modified response criteria for iNHL (Modified Cheson et al, 2007), or death from any cause on study. PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis. PFS was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley.
- Percentage of Participants With Objective Response as Assessed by IRC [Baseline until PD or death, whichever occurred first (up to approximately 5 years)]
Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. IRC review was performed up clinical cutoff date of to 1 May 2015.
- Percentage of Participants With Objective Response as Assessed by Investigator [Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)]
Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.
- Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC [Baseline until PD or death, whichever occurred first (up to approximately 5 years)]
BOR observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease & disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by baseline scan & no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic & hepatic nodules, involvement of other organs is usually assessable & no measurable disease should be present, SD: Failing to attain criteria needed for a CR/PR, but not fulfilling those for PD, PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions (e.g., splenic or hepatic nodules). IRC review was performed up clinical cutoff date of to 1 May 2015.
- Percentage of Participants With Best Overall Response (BOR) as Assessed by Investigator [Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)]
BOR: best response for a participant, observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present, SD: Failing to attain the criteria needed for a CR or PR, but not fulfilling those for PD, PD: appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in single involved node, or the size of other lesions (e.g., splenic or hepatic nodules).
- Percentage of Participants With BOR at the End of Induction Treatment as Assessed by IRC [Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1)]
BOR observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease & disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan & no new sites; no increase in size of other nodes, liver or spleen; with exception of splenic & hepatic nodules, involvement of other organs is usually assessable & no measurable disease should be present, SD: Failing to attain criteria needed for a CR/PR, but not fulfilling those for PD, PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or size of other lesions (e.g., splenic/hepatic nodules). IRC review was performed up clinical cutoff date of to 1 May 2015.
- Percentage of Participants With BOR at the End of Induction Treatment as Assessed by Investigator [Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1)]
BOR: best response for a participant, observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present, SD: Failing to attain criteria needed for a CR or PR, but not fulfilling those for PD, PD: appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules).
- Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC [Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1)]
Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. IRC review was performed up clinical cutoff date of to 1 May 2015.
- Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by Investigator [Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1)]
Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.
- Duration of Response (DoR) as Assessed by IRC [Baseline until PD or death, whichever occurred first (up to approximately 5 years)]
DoR: time from first objective response of CR/PR to first occurrence of PD/relapse/death from any cause. CR: Complete disappearance of all detectable evidence of disease & disease-related symptoms if present before therapy; liver, spleen returned to normal size; if bone marrow involved by lymphoma before treatment, infiltrate must be cleared on repeat bone marrow biopsy. PR: at least 50% measurable disease regressed vs. to baseline scan and no new sites; no increase in size of other nodes/liver/spleen, exception: splenic, hepatic nodules; other organs involved is usually assessable; no measurable disease present. PD: any new lesion >1.5 cm in any axis appear during or at end of therapy, even if other lesions are decreasing in size; at least 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions. DoR estimated using Kaplan-Meier method. IRC review performed up to clinical cutoff date 1 May 2015.
- Duration of Response (DoR) as Assessed by Investigator [Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)]
DoR: time from first objective response of CR/PR to first occurrence of PD/relapse/death from any cause. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy; liver, spleen returned to normal size (if enlarged at baseline); if bone marrow was involved by lymphoma prior to treatment, infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic, hepatic nodules; involvement of other organs is usually assessable; no presence of measurable disease. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions. DoR was estimated using Kaplan-Meier method.
- Disease-Free Survival (DFS) in Participants With CR as Assessed by IRC [Baseline until PD or death, whichever occurred first (up to approximately 5 years)]
DFS was defined as the time from the first occurrence of a documented CR until progression on the basis of the IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]) or death from any cause on study. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. DFS was estimated using Kaplan-Meier method. IRC review was performed up clinical cutoff date of to 1 May 2015.
- Disease-Free Survival (DFS) in Participants With CR as Assessed by Investigator [Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)]
DFS was defined as the time from the first occurrence of a documented CR until progression on the basis of the IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]) or death from any cause on study. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. DFS was estimated using Kaplan-Meier method.
- Event-free Survival (EFS) as Assessed by IRC [Baseline until PD or death, whichever occurred first (up to approximately 5 years)]
EFS was defined as the time between the date of randomization and the date of PD/relapse based on IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]), death from any cause on study, or start of a new anti-lymphoma therapy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. EFS was estimated using Kaplan-Meier method. IRC review was performed up clinical cutoff date of to 1 May 2015.
- Percentage of Participants Who Died [Baseline until death (up to 8.5 years overall)]
- Overall Survival (OS) [Baseline until death (up to 8.5 years overall)]
OS was defined as the time between the date of randomization and the date of death from any cause. OS was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley.
- Change From Baseline (CFB) in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)-Physical Well Being Sub-scale Score [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24]
The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Physical Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for physical well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better participant-reported outcome (PRO)/quality of life (QoL). In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- CFB in FACT-Lym-Social/Family Well-being Sub-scale Score [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24]
The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Social/family Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for social/family well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- CFB in FACT-Lym-Emotional Well-Being Sub-scale Score [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24]
The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Emotional Well-being sub-scale includes 6 items measured on 0-4 point scale. The total score for emotional well-being sub-scale is sum of each 6 items (range: 0-24). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- CFB in FACT-Lym-Functional Well-Being Sub-scale Score [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24]
The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Functional Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for functional well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- CFB in FACT-Lym-Lymphoma Sub-scale Score [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24]
The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Lymphoma scale includes 15 items measured on 0-4 point scale. The total score for lymphoma sub-scale is sum of each 15 items (range: 0-60). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- CFB in Euro Quality of Life 5 Dimension (EuroQoL-5D/EQ-5D) - Health State Profile Utility Score During Induction Phase [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4 and 14]
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). For 'Obinutuzumab + Bendamustine' arm, participants who had their follow-up Month 2 and 4 visits before start of maintenance treatment were reported in induction phase results under "CFB at Follow-up Month 2" and "CFB at Follow-up Month 4" categories.
- CFB in EuroQol 5D (EQ-5D) - Health State Profile Utility Score During Maintenance Phase [Baseline, Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final follow-up (up to 2 years after end of induction) (End of induction = up to Month 6)]
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Data for this outcome was planned to be reported only for 'Obinutuzumab + Bendamustine' arm. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). Follow-up months were during maintenance phase.
- CFB in EQ-5D Visual Analogue Scale (VAS) Score During Induction Phase [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4 and 14]
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeter (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). For 'Obinutuzumab + Bendamustine' arm, participants who had their follow-up Month 2 and 4 visits before start of maintenance treatment were reported in induction phase results under "CFB at Follow-up Month 2" and "CFB at Follow-up Month 4" categories.
- CFB in EQ-5D VAS Score During Maintenance Phase [Baseline, Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction) (end of induction = up to Month 6)]
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Data for this outcome was planned to be reported only for 'Obinutuzumab + Bendamustine' arm. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). Follow-up months were during maintenance phase.
- CFB in Functional Assessment of Cancer Therapy - Generic (FACT-G) Score [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24]
The FACT-G is the sum of 4 sub-scales (physical, social, emotional and functional well-being) of FACT-Lym which includes total 27 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-108. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- CFB in FACT-Lym Trial Outcome Index (TOI) [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24]
TOI is the sum of 3 sub-scales (physical well-being, functional well-being, and Lymphoma sub-scale) of FACT-Lym which includes total 29 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-116. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- CFB in FACT-Lym Total Score [Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24]
FACT-Lym total score is the sum of physical well-being score (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and Lymphoma sub-scale (15 items); responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- Time to Deterioration of FACT-Lym TOI [Baseline up to approximately 8.5 years]
The median time, in month, from date of randomization until a clinically meaningful decline from baseline in TOI or death, whichever occurred first. TOI: sum of physical well-being score,functional well-being score, and Lymphoma sub-scale of FACT-Lym; total 29 items, responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-116. Higher scores indicate a better PRO/QoL. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from baseline. Time to deterioration was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley. In timeframe, follow-up months represents months after end of induction (EOI) (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).
- Percentage of Participants With Definitive Improvement (DI) From Baseline in FACT-Lym Instrument Scores [Baseline, Cycle 5 Day 1 (C5D1) (Cycle length = 28 days), Follow-up Months 6 (FUM6), 12 (FUM12), 18 (FUM18), 24 (FUM24), Extension Follow Up Month 6 (Extension FUM6)]
FACT-Lym: 42-items in 5 subscales. Responses to each item range from 0 (Not at all) to 4 (Very much). FACT-Lym Lymphoma subscale includes 15 items (total score range = 0-60). FACT-Lym TOI is sum of 3 subscales (physical well-being, functional well-being, lymphoma subscale) and includes 29 items (total score range = 0-116). FACT-Lym total score is sum of 42 items (total score ranges from 0-168). For all above, higher scores indicate a better PRO/QoL. DI from baseline: at least 3 point increase from baseline in FACT-Lym Lymphoma subscale; at least 6 point increase from baseline in FACT Lym TOI; at least 7 point increase from baseline in FACT Lym total scores. In timeframe, follow-up months represents months after EOI (e.g. Follow-up Month 2 is 2 months after EOI; EOI = up to Month 6).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
History of histologically documented, B-lymphocyte antigen cluster of differentiation 20 plus (CD20+), iNHL
-
Refractory to any previous regimen containing rituximab (defined by participants who did not respond or who progressed during or up to 6 months after treatment with rituximab or a rituximab-containing regimen)
-
Previously treated with a maximum of four unique chemotherapy containing treatment regimens
-
All participants must have at least one bi-dimensionally measurable lesion (greater than [>]1.5 centimeters (cm) in its largest dimension by computed tomography [CT] scan)
Exclusion Criteria:
-
Prior use of any monoclonal antibody (other than anti-CD20) within 3 months prior to the start of Cycle 1, prior treatment with obinutuzumab was not allowed
-
Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1
-
Prior treatment with bendamustine (within 2 years of the start of Cycle 1)
-
Prior allogeneic stem cell transplant
-
History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
-
History of sensitivity to mannitol
-
Central nervous system lymphoma or prior diffuse large B-cell lymphoma (DLBCL), histological evidence of transformation to high grade or diffuse large B-cell lymphoma
-
History of other malignancy that could affect compliance with the protocol or interpretation of results
-
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
-
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 4 weeks
-
Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
-
Vaccination with a live vaccine a minimum of 28 days prior to randomization
-
Recent major surgery (within 4 weeks), other than for diagnosis
-
Presence of positive test results for Hepatitis B surface antigen (HBsAg); antibody to hepatitis B core antigen [anti-HBc]) with detectable viral load (positive hepatitis B virus [HBV] deoxyribo-nucleic acid [DNA]) or Hepatitis C
-
Participants with chronic hepatitis B or seropositive occult (HBV) infection
-
Participants with seronegative occult HBV infection or past HBV infection (defined as anti-HBc positive and HBV DNA negative) could be eligible if they were willing to be followed according to the protocol for HBV DNA testing
-
Participants positive for Hepatitis C virus (HCV) antibody were eligible only if polymerase chain reaction(PCR) was negative for HCV Ribonucleic acid (RNA)
-
Known history of human immunodeficiency virus (HIV) seropositive status
-
Positive test results for human T-lymphotropic virus type I (HTLV 1) virus in endemic countries
-
Women who are pregnant or lactating
-
Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly
-
Ongoing corticosteroid use >30 milligrams per day (mg/day) prednisone or equivalent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Southern Cancer Center, PC | Mobile | Alabama | United States | 36608 |
| 2 | Dr. Donald W. Hill, MD, FACP | Casa Grande | Arizona | United States | 85122 |
| 3 | Highlands Oncology Group | Rogers | Arkansas | United States | 72758 |
| 4 | Kaiser Permanente - Bellflower | Bellflower | California | United States | 90706 |
| 5 | Bay Area Cancer Research Group, LLC | Pleasant Hill | California | United States | 94523 |
| 6 | Sharp Memorial Hospital | San Diego | California | United States | 92123 |
| 7 | Georgetown University Medical Center Lombardi Cancer Center | Washington | District of Columbia | United States | 20007 |
| 8 | Washington DC VA Med Center; Hematology | Washington | District of Columbia | United States | 20422 |
| 9 | University of Florida | Gainesville | Florida | United States | 32607 |
| 10 | University of Florida; Division of Hematology/Oncology | Gainesville | Florida | United States | 33610-0277 |
| 11 | Md Anderson Cancer Center Orlando | Orlando | Florida | United States | 32806 |
| 12 | Rush Cancer Institute | Chicago | Illinois | United States | 60612 |
| 13 | Quincy Medical Group | Quincy | Illinois | United States | 62301 |
| 14 | Simmons Cancer Institute | Springfield | Illinois | United States | 62794-9677 |
| 15 | University of Iowa | Iowa City | Iowa | United States | 52242 |
| 16 | Univ Louisville School of Med | Louisville | Kentucky | United States | 40202 |
| 17 | New England Cancer Specialists | Scarborough | Maine | United States | 04074 |
| 18 | Meritus Center for Clinical Research | Hagerstown | Maryland | United States | 21740 |
| 19 | Capitol Comprehensive CA Care | Jefferson City | Missouri | United States | 65101 |
| 20 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 21 | Hematology Oncology Assoc SJ | Mount Holly | New Jersey | United States | 08060 |
| 22 | San Juan Oncology | Farmington | New Mexico | United States | 87401 |
| 23 | The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc. | Columbus | Ohio | United States | 43219 |
| 24 | OHSU Knight Cancer Institute | Portland | Oregon | United States | 97210 |
| 25 | Pacific Oncology, PC | Portland | Oregon | United States | 97210 |
| 26 | OHSU Ctr for Health & Healing | Portland | Oregon | United States | 97239 |
| 27 | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | United States | 19107 |
| 28 | Western Pennsylvania Hospital | Pittsburgh | Pennsylvania | United States | 15224 |
| 29 | Sanford Health System | Sioux Falls | South Dakota | United States | 57105 |
| 30 | South Texas Inst of Cancer | Corpus Christi | Texas | United States | 78405 |
| 31 | University of Texas M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 32 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 98109 |
| 33 | Univ of Wisconsin Hosp & Clin | Madison | Wisconsin | United States | 53792 |
| 34 | Lkh-Univ. Klinikum Graz | Graz | Austria | 8036 | |
| 35 | Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt. | Salzburg | Austria | 5020 | |
| 36 | Medizinische Universität Wien | Wien | Austria | 1090 | |
| 37 | ZNA Stuivenberg | Antwerpen | Belgium | 2060 | |
| 38 | AZ Groeninge | Kortrijk | Belgium | 8500 | |
| 39 | CHU Ambroise Paré | Mons | Belgium | 7000 | |
| 40 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
| 41 | British Columbia Cancer Agency | Kelowna | British Columbia | Canada | V1Y 5L3 |
| 42 | British Columbia Cancer Agency | Vancouver | British Columbia | Canada | V5Z 1H6 |
| 43 | Manitoba Cancer Care | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 44 | Moncton Hospital | Moncton | New Brunswick | Canada | E1C 6Z8 |
| 45 | Toronto East General Hospital; Main Pharmacy G Wing Basement | East York | Ontario | Canada | M4C 3E7 |
| 46 | Princess Margaret Hospital | Toronto | Ontario | Canada | M4X 1K9 |
| 47 | CHUM-Hosp Notre Dame | Montreal | Quebec | Canada | H2X 3E4 |
| 48 | McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology | Montreal | Quebec | Canada | H3T 1E2 |
| 49 | CHA Hopital de I enfant-Jesus | Quebec City | Quebec | Canada | G1J 1Z4 |
| 50 | Allan Blair Cancer Centre | Regina | Saskatchewan | Canada | S4T 7T1 |
| 51 | Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika | Brno | Czechia | 625 00 | |
| 52 | Fakultni nemocnice Hradec Kralove | Hradec Kralove | Czechia | 500 05 | |
| 53 | I Interni klinika; Vseobecna fakultni nemocnice | Prague 2 | Czechia | 128 08 | |
| 54 | Institut Bergonie; Hematologie Oncologie | Bordeaux | France | 33076 | |
| 55 | Polyclinique Bordeaux Nord | Bordeaux | France | 33300 | |
| 56 | Hopital Henri Mondor | Creteil | France | 94010 | |
| 57 | CH Dijon | Dijon | France | 21079 | |
| 58 | Centre d'oncologie-radiotherap | LeMans | France | 72015 | |
| 59 | Hopital Claude Huriez | Lille | France | 59037 | |
| 60 | Centre Leon Berard | Lyon | France | 69008 | |
| 61 | Hopital Bon Secour | Metz | France | 57038 | |
| 62 | CHU Hopital Saint Eloi | Montpellier | France | 34295 | |
| 63 | Hopital Hotel Dieu Et Hme; Clinique Dermatologique | Nantes | France | 44093 | |
| 64 | Hopital Necker | Paris | France | 75015 | |
| 65 | Hopital Saint Louis; Dermatologie 1 | Paris | France | 75475 | |
| 66 | CHU Bordeaux | Pessac | France | 33604 | |
| 67 | Centre Hospitalier Lyon Sud; Hematolgie | Pierre Benite | France | 69495 | |
| 68 | Chu De Poitiers; Chu La Miletrie | Poitiers | France | 86021 | |
| 69 | CHU de Reims | Reims | France | 51100 | |
| 70 | Hopital Pontchaillou | Rennes | France | 35033 | |
| 71 | Centre Henri Becquerel | Rouen | France | 76038 | |
| 72 | Clinique Ste Anne | Strasbourg | France | 67000 | |
| 73 | CHRU de; Maladies, Vasculaires | Vandoeuvre | France | 54511 | |
| 74 | St. Johannes Hospital Duisburg | Duisburg | Germany | 47166 | |
| 75 | Klinikum Frankfurt Höchst | Frankfurt am Main | Germany | 65929 | |
| 76 | Asklepios Klinik St. Georg | Hamburg | Germany | 20099 | |
| 77 | Universitaetsklinikum Leipzig | Leipzig | Germany | 04103 | |
| 78 | Klinikum der Universitat Munchen, Campus Grobhadern;; Medizinische Klinik und Poliklinik III | München | Germany | 81377 | |
| 79 | Schwarzwald-Baar Klinikum GmbH | Villingen-Schwenningen | Germany | 78052 | |
| 80 | Azienda Ospedaliera Universitaria di Modena | Modena | Emilia-Romagna | Italy | 41100 |
| 81 | Azienda Ospedaliera Univ, Ematologica | Udine | Friuli-Venezia Giulia | Italy | 33100 |
| 82 | Azienda Ospedaliera Univ | Roma | Lazio | Italy | 00133 |
| 83 | Universita La Sapienza | Roma | Lazio | Italy | 00161 |
| 84 | Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2 | Milano | Lombardia | Italy | 20133 |
| 85 | Irccs Policlinico San Matteo; Divisione Di Ematologia | Pavia | Lombardia | Italy | 27100 |
| 86 | Azienda Ospedale San Giovanni | Torino | Piemonte | Italy | 10126 |
| 87 | Ospedale Mauriziano Umberto I | Torino | Piemonte | Italy | 10128 |
| 88 | Ospedale Vito Fazzi | Lecce | Puglia | Italy | 73100 |
| 89 | Azienda Ospedaliero Univ | Catania | Sicilia | Italy | 95124 |
| 90 | Azienda Ospedaliera Univ | Firenze | Toscana | Italy | 50141 |
| 91 | VU MEDISCH CENTRUM; Dept. of Medical Oncology | Amsterdam | Netherlands | 1081 HV | |
| 92 | Haga Ziekenhuis | Den Haag | Netherlands | 2504 LN | |
| 93 | Albert Schweitzer Ziekenhuis | Dordrecht | Netherlands | 3371 NM | |
| 94 | Universitair Medisch Centrum Groningen | Groningen | Netherlands | 9713 GZ | |
| 95 | Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology | Rotterdam | Netherlands | 3015 CE | |
| 96 | Erasmus MC | Rotterdam | Netherlands | 3015 GD | |
| 97 | Regional Oncology Hospital | Irkutsk | Russian Federation | 664035 | |
| 98 | Blokhin Cancer Research Center; Combined Treatment | Moscow | Russian Federation | 115478 | |
| 99 | City Clin Hosp n.a. S.P.Botkin | Moscow | Russian Federation | 125101 | |
| 100 | Russian Hema Res Ctr of RAMS | Moscow | Russian Federation | 125167 | |
| 101 | Republican Clinical Hospital n.a. Baranov; Haematology | Petrozavodsk | Russian Federation | 185019 | |
| 102 | Ryazan Regional Clinical Hosp | Ryazan | Russian Federation | 390039 | |
| 103 | St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta | Saint-Petersburg | Russian Federation | 197022 | |
| 104 | SRI of Hematology and Transfusiology | St. Petersburg | Russian Federation | 191024 | |
| 105 | Clinica Universitaria de Navarra | Pamplona | Navarra | Spain | 31008 |
| 106 | Hospital Univ. Nuestra Señora de Valme; | Sevillac | Sevilla | Spain | 41014 |
| 107 | Hospital Universitario Basurto | Bilbao | Vizcaya | Spain | 48013 |
| 108 | Hospital Universitario de la Princesa; Servicio de Hematologia | Madrid | Spain | 28006 | |
| 109 | Hospital Universitario La Paz | Madrid | Spain | 28034 | |
| 110 | Skånes University Hospital, Skånes Department of Onclology | Lund | Sweden | 22185 | |
| 111 | Hematology Center; Karolinska Univ Hosp | Stockholm | Sweden | 14186 | |
| 112 | Norrlands Uni Hospital; Onkologi Avd. | Umeå | Sweden | 901 85 | |
| 113 | Onc Clin, Akademiska Sjukhuset | Uppsala | Sweden | 751 85 | |
| 114 | Universitaetsspital Basel; Onkologie | Basel | Switzerland | 4031 | |
| 115 | Inselspital Bern; Universitätsklinik für medizinische Onkologie | Bern | Switzerland | 3010 | |
| 116 | Kantonsspital Graubünden;Onkologie und Hämatologie | Chur | Switzerland | 7000 | |
| 117 | Beatson West of Scotland Cancer Centre | Glasgow | United Kingdom | G12 0YN | |
| 118 | Leicester Royal Infirmary | Leicester | United Kingdom | LE1 5WW | |
| 119 | Barts & London School of Med; Medical Oncology | London | United Kingdom | EC1A 7BE | |
| 120 | Freeman Hospital | Newcastle upon Tyne | United Kingdom | NE7 7DN | |
| 121 | Singleton Hospital; Pharmacy Department | Swansea | United Kingdom | SA2 8QA |
Sponsors and Collaborators
- Genentech, Inc.
- Roche Pharma AG
Investigators
- Study Director: Clinical Trials, Genentech, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GAO4753g
- GO01297
- 2009-015504-25
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Period Title: Overall Study | ||
| STARTED | 209 | 204 |
| COMPLETED | 82 | 101 |
| NOT COMPLETED | 127 | 103 |
Baseline Characteristics
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine | Total |
|---|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). | Total of all reporting groups |
| Overall Participants | 209 | 204 | 413 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
61.9
(11.5)
|
62.0
(11.3)
|
61.9
(11.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
87
41.6%
|
88
43.1%
|
175
42.4%
|
| Male |
122
58.4%
|
116
56.9%
|
238
57.6%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Hispanic or Latino |
5
2.4%
|
6
2.9%
|
11
2.7%
|
| Not Hispanic or Latino |
174
83.3%
|
183
89.7%
|
357
86.4%
|
| Not Stated |
30
14.4%
|
15
7.4%
|
45
10.9%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| American Indian or Alaska Native |
2
1%
|
1
0.5%
|
3
0.7%
|
| Asian |
3
1.4%
|
6
2.9%
|
9
2.2%
|
| Black or African American |
3
1.4%
|
5
2.5%
|
8
1.9%
|
| Multiple |
1
0.5%
|
0
0%
|
1
0.2%
|
| Unknown |
19
9.1%
|
12
5.9%
|
31
7.5%
|
| White |
181
86.6%
|
180
88.2%
|
361
87.4%
|
Outcome Measures
| Title | Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death |
|---|---|
| Description | PD was assessed by an IRC according to the modified response criteria for indolent Non-Hodgkin's Lymphoma (iNHL) (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50 percent (%) increase from nadir in the sum of product diameter (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions (example: splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of less than (<) 1.0 cm must increase by greater than or equal to (≥) 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node greater than (>) 1 cm in its short axis. |
| Time Frame | Baseline until PD or death, whichever occurred first (assessed at baseline, 14 days prior to Cycle [Cy] 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1, then every 3 months up to 2 years and every 6 months for next 2 years [up to 4.5 years overall]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Number [participants] |
125
59.8%
|
87
42.6%
|
| Title | Progression-Free Survival (PFS) as Assessed by IRC |
|---|---|
| Description | PFS was defined as the time from randomization to the first occurrence of PD or death as assessed by an IRC according to the modified response criteria for iNHL (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be PD, a lymph node with a diameter of the short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis. PFS was estimated using Kaplan-Meier method and 95% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley. |
| Time Frame | Baseline until PD or death, whichever occurred first (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1, then every 3 months up to 2 years and every 6 months for next 2 years [up to 4.5 years overall]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Median (95% Confidence Interval) [months] |
14.1
|
29.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.53 | |
| Confidence Interval |
(2-Sided) 95% 0.40 to 0.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With PD or Death as Assessed by Investigator |
|---|---|
| Description | PD was assessed by an investigator according to the modified response criteria for iNHL (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to 8.5 years overall)) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Number [participants] |
152
72.7%
|
132
64.7%
|
| Title | PFS as Assessed by Investigator |
|---|---|
| Description | PFS was defined as the time from randomization to the first occurrence of PD as assessed by an investigator according to the modified response criteria for iNHL (Modified Cheson et al, 2007), or death from any cause on study. PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis. PFS was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to 8.5 years overall) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Median (95% Confidence Interval) [months] |
14.1
|
25.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.57 | |
| Confidence Interval |
(2-Sided) 95% 0.45 to 0.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Objective Response as Assessed by IRC |
|---|---|
| Description | Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. IRC review was performed up clinical cutoff date of to 1 May 2015. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had at least one post-baseline assessment. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Number (95% Confidence Interval) [percentage of participants] |
77.5
37.1%
|
75.5
37%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9298 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in response rate |
| Estimated Value | 0.98 | |
| Confidence Interval |
(2-Sided) 95% 0.58 to 1.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Objective Response as Assessed by Investigator |
|---|---|
| Description | Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 8.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had at least one post-baseline assessment. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Number (95% Confidence Interval) [percentage of participants] |
83.3
39.9%
|
82.4
40.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7857 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in response rate |
| Estimated Value | -0.90 | |
| Confidence Interval |
(2-Sided) 95% -8.44 to 6.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC |
|---|---|
| Description | BOR observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease & disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by baseline scan & no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic & hepatic nodules, involvement of other organs is usually assessable & no measurable disease should be present, SD: Failing to attain criteria needed for a CR/PR, but not fulfilling those for PD, PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions (e.g., splenic or hepatic nodules). IRC review was performed up clinical cutoff date of to 1 May 2015. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had at least one post-baseline assessment. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| CR |
17.2
8.2%
|
16.2
7.9%
|
| PR |
60.3
28.9%
|
59.3
29.1%
|
| SD |
12.0
5.7%
|
13.7
6.7%
|
| PD |
5.7
2.7%
|
4.9
2.4%
|
| Unable to evaluate |
1.0
0.5%
|
1.0
0.5%
|
| Missing |
3.8
1.8%
|
4.9
2.4%
|
| Title | Percentage of Participants With Best Overall Response (BOR) as Assessed by Investigator |
|---|---|
| Description | BOR: best response for a participant, observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present, SD: Failing to attain the criteria needed for a CR or PR, but not fulfilling those for PD, PD: appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 8.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had at least one post-baseline assessment. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| CR |
21.5
10.3%
|
23.5
11.5%
|
| PR |
61.7
29.5%
|
58.8
28.8%
|
| SD |
6.7
3.2%
|
6.4
3.1%
|
| PD |
4.8
2.3%
|
6.4
3.1%
|
| Unable to evaluate |
1.4
0.7%
|
0.5
0.2%
|
| Missing |
3.8
1.8%
|
4.4
2.2%
|
| Title | Percentage of Participants With BOR at the End of Induction Treatment as Assessed by IRC |
|---|---|
| Description | BOR observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease & disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan & no new sites; no increase in size of other nodes, liver or spleen; with exception of splenic & hepatic nodules, involvement of other organs is usually assessable & no measurable disease should be present, SD: Failing to attain criteria needed for a CR/PR, but not fulfilling those for PD, PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or size of other lesions (e.g., splenic/hepatic nodules). IRC review was performed up clinical cutoff date of to 1 May 2015. |
| Time Frame | Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had reached the end of induction treatment response assessment. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| CR |
12.0
5.7%
|
11.8
5.8%
|
| PR |
52.4
25.1%
|
54.9
26.9%
|
| SD |
10.1
4.8%
|
11.8
5.8%
|
| PD |
10.6
5.1%
|
8.8
4.3%
|
| Unable to Evaluate |
2.9
1.4%
|
2.0
1%
|
| Missing |
12.0
5.7%
|
10.8
5.3%
|
| Title | Percentage of Participants With BOR at the End of Induction Treatment as Assessed by Investigator |
|---|---|
| Description | BOR: best response for a participant, observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present, SD: Failing to attain criteria needed for a CR or PR, but not fulfilling those for PD, PD: appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). |
| Time Frame | Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had reached the end of induction treatment response assessment. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| CR |
15.8
7.6%
|
17.2
8.4%
|
| PR |
53.1
25.4%
|
60.3
29.6%
|
| SD |
4.3
2.1%
|
3.9
1.9%
|
| PD |
12.0
5.7%
|
9.3
4.6%
|
| Unable to Evaluate |
2.9
1.4%
|
0.5
0.2%
|
| Missing |
12.0
5.7%
|
8.8
4.3%
|
| Title | Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC |
|---|---|
| Description | Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. IRC review was performed up clinical cutoff date of to 1 May 2015. |
| Time Frame | Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had reached the end of induction treatment response assessment. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Number (95% Confidence Interval) [percentage of participants] |
64.4
30.8%
|
66.7
32.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8347 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in response rate |
| Estimated Value | 2.24 | |
| Confidence Interval |
(2-Sided) 95% -7.20 to 11.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by Investigator |
|---|---|
| Description | Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. |
| Time Frame | Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had reached the end of induction treatment response assessment. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Number (95% Confidence Interval) [percentage of participants] |
68.9
33%
|
77.5
38%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0466 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in response rate |
| Estimated Value | 8.55 | |
| Confidence Interval |
(2-Sided) 95% -0.22 to 17.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Response (DoR) as Assessed by IRC |
|---|---|
| Description | DoR: time from first objective response of CR/PR to first occurrence of PD/relapse/death from any cause. CR: Complete disappearance of all detectable evidence of disease & disease-related symptoms if present before therapy; liver, spleen returned to normal size; if bone marrow involved by lymphoma before treatment, infiltrate must be cleared on repeat bone marrow biopsy. PR: at least 50% measurable disease regressed vs. to baseline scan and no new sites; no increase in size of other nodes/liver/spleen, exception: splenic, hepatic nodules; other organs involved is usually assessable; no measurable disease present. PD: any new lesion >1.5 cm in any axis appear during or at end of therapy, even if other lesions are decreasing in size; at least 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions. DoR estimated using Kaplan-Meier method. IRC review performed up to clinical cutoff date 1 May 2015. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had objective response at any time during the study. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 165 | 158 |
| Median (95% Confidence Interval) [months] |
12.7
|
38.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.43 | |
| Confidence Interval |
(2-Sided) 95% 0.31 to 0.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Response (DoR) as Assessed by Investigator |
|---|---|
| Description | DoR: time from first objective response of CR/PR to first occurrence of PD/relapse/death from any cause. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy; liver, spleen returned to normal size (if enlarged at baseline); if bone marrow was involved by lymphoma prior to treatment, infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic, hepatic nodules; involvement of other organs is usually assessable; no presence of measurable disease. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions. DoR was estimated using Kaplan-Meier method. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 8.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had objective response at any time during the study. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Median (95% Confidence Interval) [months] |
12.7
|
32.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.51 | |
| Confidence Interval |
(2-Sided) 95% 0.39 to 0.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Disease-Free Survival (DFS) in Participants With CR as Assessed by IRC |
|---|---|
| Description | DFS was defined as the time from the first occurrence of a documented CR until progression on the basis of the IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]) or death from any cause on study. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. DFS was estimated using Kaplan-Meier method. IRC review was performed up clinical cutoff date of to 1 May 2015. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had an objective response of CR. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 37 | 46 |
| Median (95% Confidence Interval) [months] |
13.2
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% 0.04 to 0.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Disease-Free Survival (DFS) in Participants With CR as Assessed by Investigator |
|---|---|
| Description | DFS was defined as the time from the first occurrence of a documented CR until progression on the basis of the IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]) or death from any cause on study. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. DFS was estimated using Kaplan-Meier method. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 8.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who had an objective response of CR. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Median (95% Confidence Interval) [months] |
20.0
|
36.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.48 | |
| Confidence Interval |
(2-Sided) 95% 0.29 to 0.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Event-free Survival (EFS) as Assessed by IRC |
|---|---|
| Description | EFS was defined as the time between the date of randomization and the date of PD/relapse based on IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]), death from any cause on study, or start of a new anti-lymphoma therapy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. EFS was estimated using Kaplan-Meier method. IRC review was performed up clinical cutoff date of to 1 May 2015. |
| Time Frame | Baseline until PD or death, whichever occurred first (up to approximately 5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Median (95% Confidence Interval) [months] |
13.7
|
25.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.57 | |
| Confidence Interval |
(2-Sided) 95% 0.44 to 0.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Died |
|---|---|
| Description | |
| Time Frame | Baseline until death (up to 8.5 years overall) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 203 | 204 |
| Number [percentage of participants] |
49.3
23.6%
|
41.2
20.2%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time between the date of randomization and the date of death from any cause. OS was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley. |
| Time Frame | Baseline until death (up to 8.5 years overall) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Median (95% Confidence Interval) [months] |
65.6
|
88.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bendamustine Alone, Obinutuzumab + Bendamustine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0810 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.77 | |
| Confidence Interval |
(2-Sided) 95% 0.57 to 1.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline (CFB) in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)-Physical Well Being Sub-scale Score |
|---|---|
| Description | The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Physical Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for physical well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better participant-reported outcome (PRO)/quality of life (QoL). In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 187 | 187 |
| Baseline |
22.58
(5.23)
|
22.76
(4.61)
|
| CFB at Cycle 3 Day 1 |
-1.56
(5.49)
|
-0.69
(4.06)
|
| CFB at Cycle 4 Day 1 |
-6.80
(4.21)
|
-3.00
(2.83)
|
| CFB at Cycle 5 Day 1 |
-1.82
(5.06)
|
-0.72
(4.16)
|
| CFB at End of Induction Treatment |
-1.00
(5.14)
|
-0.61
(4.62)
|
| CFB at Follow-up Month 2 |
0.62
(5.14)
|
0.58
(4.45)
|
| CFB at Follow-up Month 4 |
0.53
(4.58)
|
0.88
(4.47)
|
| CFB at Follow-up Month 6 |
0.29
(3.74)
|
0.91
(3.82)
|
| CFB at Follow-up Month 8 |
-0.01
(3.53)
|
0.87
(3.96)
|
| CFB at Follow-up Month 10 |
0.06
(4.16)
|
0.56
(3.81)
|
| CFB at Follow-up Month 12 |
0.26
(4.02)
|
0.74
(4.24)
|
| CFB at Follow-up Month 14 |
0.03
(4.14)
|
0.71
(3.94)
|
| CFB at Follow-up Month 16 |
-0.10
(3.49)
|
1.31
(3.68)
|
| CFB at Follow-up Month 18 |
-0.22
(3.64)
|
0.92
(3.99)
|
| CFB at Follow-up Month 20 |
-0.36
(3.70)
|
0.74
(3.69)
|
| CFB at Follow-up Month 22 |
-0.25
(3.93)
|
0.40
(4.47)
|
| CFB at Follow-up Month 24 |
-0.77
(4.16)
|
0.52
(4.42)
|
| CFB at Final Follow-up |
0.16
(4.17)
|
0.22
(4.47)
|
| CFB at Extension Follow-up Month 6 |
0.36
(3.48)
|
0.57
(4.71)
|
| CFB at Extension Follow-up Month 18 |
0.80
(2.54)
|
1.19
(4.98)
|
| CFB at Extension Follow-up Month 24 |
1.53
(5.96)
|
0.56
(5.26)
|
| Title | CFB in FACT-Lym-Social/Family Well-being Sub-scale Score |
|---|---|
| Description | The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Social/family Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for social/family well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 186 | 191 |
| Baseline |
22.04
(5.65)
|
22.14
(5.51)
|
| CFB at Cycle 3 Day 1 |
-0.21
(3.59)
|
-0.10
(3.87)
|
| CFB at Cycle 4 Day 1 |
-1.00
(3.67)
|
3.11
(2.83)
|
| CFB at Cycle 5 Day 1 |
-0.34
(4.32)
|
-0.34
(4.33)
|
| CFB at End of Induction Treatment |
-0.65
(5.21)
|
-0.88
(3.60)
|
| CFB at Follow-up Month 2 |
-0.02
(4.83)
|
-0.57
(5.37)
|
| CFB at Follow-up Month 4 |
0.27
(4.65)
|
-0.26
(5.02)
|
| CFB at Follow-up Month 6 |
0.05
(4.46)
|
-0.08
(4.64)
|
| CFB at Follow-up Month 8 |
-0.68
(3.67)
|
-0.37
(4.99)
|
| CFB at Follow-up Month 10 |
0.56
(5.00)
|
0.13
(5.14)
|
| CFB at Follow-up Month 12 |
0.06
(5.89)
|
-0.47
(5.64)
|
| CFB at Follow-up Month 14 |
0.56
(3.28)
|
-0.03
(4.16)
|
| CFB at Follow-up Month 16 |
0.36
(6.79)
|
-0.15
(5.28)
|
| CFB at Follow-up Month 18 |
0.44
(6.23)
|
0.04
(5.35)
|
| CFB at Follow-up Month 20 |
-0.66
(4.28)
|
0.00
(5.75)
|
| CFB at Follow-up Month 22 |
0.29
(7.12)
|
-0.50
(5.02)
|
| CFB at Follow-up Month 24 |
-1.29
(3.91)
|
-0.41
(5.24)
|
| CFB at Final Follow-up |
-0.19
(4.91)
|
-0.52
(5.56)
|
| CFB at Extension Follow-up Month 6 |
-0.35
(2.49)
|
-0.16
(4.92)
|
| CFB at Extension Follow-up Month 18 |
-0.15
(2.92)
|
0.71
(5.26)
|
| CFB at Extension Follow-up Month 24 |
-0.41
(3.18)
|
0.44
(5.02)
|
| Title | CFB in FACT-Lym-Emotional Well-Being Sub-scale Score |
|---|---|
| Description | The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Emotional Well-being sub-scale includes 6 items measured on 0-4 point scale. The total score for emotional well-being sub-scale is sum of each 6 items (range: 0-24). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 189 | 193 |
| Baseline |
17.38
(4.45)
|
17.81
(4.33)
|
| CFB at Cycle 3 Day 1 |
0.61
(3.04)
|
0.78
(3.14)
|
| CFB at Cycle 4 Day 1 |
-0.60
(3.85)
|
3.40
(4.42)
|
| CFB at Cycle 5 Day 1 |
0.37
(3.08)
|
0.50
(3.52)
|
| CFB at End of Induction Treatment |
0.53
(3.57)
|
0.59
(4.03)
|
| CFB at Follow-up Month 2 |
0.66
(3.89)
|
0.67
(3.83)
|
| CFB at Follow-up Month 4 |
1.34
(3.54)
|
0.95
(3.51)
|
| CFB at Follow-up Month 6 |
0.89
(3.57)
|
0.96
(3.44)
|
| CFB at Follow-up Month 8 |
0.26
(3.35)
|
0.97
(3.34)
|
| CFB at Follow-up Month 10 |
0.69
(3.31)
|
1.32
(3.23)
|
| CFB at Follow-up Month 12 |
-0.07
(3.88)
|
0.95
(3.29)
|
| CFB at Follow-up Month 14 |
0.46
(3.22)
|
1.07
(3.82)
|
| CFB at Follow-up Month 16 |
0.13
(3.87)
|
1.04
(3.69)
|
| CFB at Follow-up Month 18 |
0.42
(3.36)
|
1.00
(3.38)
|
| CFB at Follow-up Month 20 |
-0.43
(2.90)
|
0.94
(4.28)
|
| CFB at Follow-up Month 22 |
0.18
(2.81)
|
0.97
(3.79)
|
| CFB at Follow-up Month 24 |
0.06
(3.20)
|
1.12
(3.78)
|
| CFB at Final Follow-up |
0.38
(3.77)
|
0.34
(4.37)
|
| CFB at Extension Follow-up Month 6 |
-0.44
(3.26)
|
0.39
(3.99)
|
| CFB at Extension Follow-up Month 18 |
-0.08
(3.80)
|
0.75
(3.85)
|
| CFB at Extension Follow-up Month 24 |
1.04
(4.16)
|
0.97
(4.36)
|
| Title | CFB in FACT-Lym-Functional Well-Being Sub-scale Score |
|---|---|
| Description | The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Functional Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for functional well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 189 | 196 |
| Baseline |
17.98
(6.31)
|
17.90
(6.08)
|
| CFB at Cycle 3 Day 1 |
-0.54
(4.65)
|
0.38
(4.66)
|
| CFB at Cycle 4 Day 1 |
-0.80
(2.28)
|
1.78
(4.91)
|
| CFB at Cycle 5 Day 1 |
-0.71
(5.04)
|
0.67
(5.35)
|
| CFB at End of Induction Treatment |
-0.50
(5.50)
|
0.00
(5.25)
|
| CFB at Follow-up Month 2 |
0.31
(5.27)
|
0.65
(5.38)
|
| CFB at Follow-up Month 4 |
0.24
(5.11)
|
1.31
(5.86)
|
| CFB at Follow-up Month 6 |
0.95
(4.58)
|
1.26
(5.08)
|
| CFB at Follow-up Month 8 |
-0.27
(4.38)
|
0.92
(5.45)
|
| CFB at Follow-up Month 10 |
1.09
(4.25)
|
1.00
(5.52)
|
| CFB at Follow-up Month 12 |
0.18
(5.59)
|
1.78
(6.04)
|
| CFB at Follow-up Month 14 |
1.16
(4.27)
|
1.22
(4.84)
|
| CFB at Follow-up Month 16 |
0.91
(3.97)
|
1.69
(5.95)
|
| CFB at Follow-up Month 18 |
0.21
(4.12)
|
1.84
(5.77)
|
| CFB at Follow-up Month 20 |
-0.27
(4.90)
|
1.43
(6.14)
|
| CFB at Follow-up Month 22 |
-0.32
(5.70)
|
0.82
(5.00)
|
| CFB at Follow-up Month 24 |
-0.96
(4.36)
|
0.98
(5.87)
|
| CFB at Final Follow-up |
-0.08
(4.94)
|
0.50
(6.19)
|
| CFB at Extension Follow-up Month 6 |
1.01
(3.51)
|
0.85
(6.65)
|
| CFB at Extension Follow-up Month 18 |
0.96
(4.51)
|
1.90
(6.50)
|
| CFB at Extension Follow-up Month 24 |
2.22
(3.34)
|
2.62
(6.95)
|
| Title | CFB in FACT-Lym-Lymphoma Sub-scale Score |
|---|---|
| Description | The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Lymphoma scale includes 15 items measured on 0-4 point scale. The total score for lymphoma sub-scale is sum of each 15 items (range: 0-60). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 189 | 194 |
| Baseline |
44.79
(9.66)
|
45.61
(9.17)
|
| CFB at Cycle 3 Day 1 |
0.98
(6.97)
|
1.24
(5.71)
|
| CFB at Cycle 4 Day 1 |
-2.80
(5.76)
|
9.50
(3.54)
|
| CFB at Cycle 5 Day 1 |
0.75
(6.79)
|
1.41
(6.21)
|
| CFB at End of Induction Treatment |
1.64
(7.10)
|
0.74
(7.89)
|
| CFB at Follow-up Month 2 |
3.44
(6.78)
|
2.45
(6.22)
|
| CFB at Follow-up Month 4 |
2.77
(6.71)
|
2.39
(6.54)
|
| CFB at Follow-up Month 6 |
2.33
(6.44)
|
3.00
(7.05)
|
| CFB at Follow-up Month 8 |
1.79
(6.01)
|
2.52
(6.69)
|
| CFB at Follow-up Month 10 |
1.90
(6.78)
|
2.28
(6.82)
|
| CFB at Follow-up Month 12 |
2.12
(6.47)
|
2.89
(6.42)
|
| CFB at Follow-up Month 14 |
0.48
(6.64)
|
2.58
(6.37)
|
| CFB at Follow-up Month 16 |
0.44
(7.79)
|
3.27
(6.14)
|
| CFB at Follow-up Month 18 |
1.18
(6.09)
|
2.91
(6.79)
|
| CFB at Follow-up Month 20 |
0.57
(7.43)
|
2.83
(6.41)
|
| CFB at Follow-up Month 22 |
1.89
(8.62)
|
2.55
(6.58)
|
| CFB at Follow-up Month 24 |
0.66
(7.59)
|
2.73
(6.48)
|
| CFB at Final Follow-up |
1.62
(7.17)
|
1.33
(7.38)
|
| CFB at Extension Follow-up Month 6 |
0.92
(5.06)
|
2.98
(7.22)
|
| CFB at Extension Follow-up Month 18 |
1.80
(8.30)
|
2.35
(5.72)
|
| CFB at Extension Follow-up Month 24 |
4.89
(6.67)
|
2.23
(6.85)
|
| Title | CFB in Euro Quality of Life 5 Dimension (EuroQoL-5D/EQ-5D) - Health State Profile Utility Score During Induction Phase |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). For 'Obinutuzumab + Bendamustine' arm, participants who had their follow-up Month 2 and 4 visits before start of maintenance treatment were reported in induction phase results under "CFB at Follow-up Month 2" and "CFB at Follow-up Month 4" categories. |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 186 | 193 |
| Baseline |
0.77
(0.22)
|
0.79
(0.20)
|
| CFB at Cycle 3 Day 1 |
0.03
(0.21)
|
0.00
(0.19)
|
| CFB at Cycle 4 Day 1 |
-0.10
(0.23)
|
-0.07
(0.41)
|
| CFB at Cycle 5 Day 1 |
0.01
(0.21)
|
0.02
(0.20)
|
| CFB at End of Induction Treatment |
0.01
(0.22)
|
0.01
(0.20)
|
| CFB at Follow-up Month 2 |
0.06
(0.24)
|
0.04
(0.18)
|
| CFB at Follow-up Month 4 |
-0.12
(0.00)
|
|
| CFB at Follow-up Month 14 |
0.12
(NA)
|
| Title | CFB in EuroQol 5D (EQ-5D) - Health State Profile Utility Score During Maintenance Phase |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Data for this outcome was planned to be reported only for 'Obinutuzumab + Bendamustine' arm. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). Follow-up months were during maintenance phase. |
| Time Frame | Baseline, Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final follow-up (up to 2 years after end of induction) (End of induction = up to Month 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population (Obinutuzumab + Bendamustine arm only). Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 2 | 158 |
| CFB at Follow-up Month 2 |
-0.15
(0.22)
|
|
| CFB at Follow-up Month 4 |
0.15
(NA)
|
0.03
(0.22)
|
| CFB at Follow-up Month 6 |
0.15
(NA)
|
0.04
(0.19)
|
| CFB at Follow-up Month 8 |
0.15
(NA)
|
0.04
(0.21)
|
| CFB at Follow-up Month 10 |
0.15
(NA)
|
0.03
(0.20)
|
| CFB at Follow-up Month 12 |
0.06
(0.18)
|
|
| CFB at Follow-up Month 14 |
0.06
(0.19)
|
|
| CFB at Follow-up Month 16 |
0.05
(0.19)
|
|
| CFB at Follow-up Month 18 |
0.05
(0.18)
|
|
| CFB at Follow-up Month 20 |
0.05
(0.20)
|
|
| CFB at Follow-up Month 22 |
0.05
(0.24)
|
|
| CFB at Follow-up Month 24 |
0.03
(0.22)
|
|
| CFB at Final Follow-up |
0.03
(0.25)
|
| Title | CFB in EQ-5D Visual Analogue Scale (VAS) Score During Induction Phase |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeter (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). For 'Obinutuzumab + Bendamustine' arm, participants who had their follow-up Month 2 and 4 visits before start of maintenance treatment were reported in induction phase results under "CFB at Follow-up Month 2" and "CFB at Follow-up Month 4" categories. |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 183 | 188 |
| Baseline |
69.48
(20.71)
|
68.03
(21.69)
|
| CFB at Cycle 3 Day 1 |
0.91
(19.38)
|
3.32
(15.99)
|
| CFB at Cycle 4 Day 1 |
-14.00
(33.29)
|
-4.33
(42.15)
|
| CFB at Cycle 5 Day 1 |
0.35
(20.79)
|
5.17
(17.35)
|
| CFB at End of Induction Treatment |
5.71
(61.88)
|
5.82
(22.20)
|
| CFB at Follow-up Month 2 |
5.19
(19.12)
|
6.85
(18.95)
|
| CFB at Follow-up Month 4 |
0.00
(14.14)
|
|
| CFB at Follow-up Month 14 |
10.00
(NA)
|
| Title | CFB in EQ-5D VAS Score During Maintenance Phase |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Data for this outcome was planned to be reported only for 'Obinutuzumab + Bendamustine' arm. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). Follow-up months were during maintenance phase. |
| Time Frame | Baseline, Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction) (end of induction = up to Month 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population (Obinutuzumab + Bendamustine arm only). Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 2 | 158 |
| CFB at Follow-up Month 2 |
-40.00
(NA)
|
|
| CFB at Follow-up Month 4 |
5.00
(NA)
|
5.59
(19.61)
|
| CFB at Follow-up Month 6 |
5.00
(NA)
|
6.04
(19.00)
|
| CFB at Follow-up Month 8 |
5.00
(NA)
|
4.79
(17.18)
|
| CFB at Follow-up Month 10 |
-15.00
(NA)
|
4.62
(16.28)
|
| CFB at Follow-up Month 12 |
5.73
(16.04)
|
|
| CFB at Follow-up Month 14 |
5.45
(17.36)
|
|
| CFB at Follow-up Month 16 |
6.66
(17.44)
|
|
| CFB at Follow-up Month 18 |
6.13
(19.44)
|
|
| CFB at Follow-up Month 20 |
7.56
(15.43)
|
|
| CFB at Follow-up Month 22 |
6.97
(15.55)
|
|
| CFB at Follow-up Month 24 |
8.28
(16.23)
|
|
| CFB at Final Follow-up |
4.47
(14.91)
|
| Title | CFB in Functional Assessment of Cancer Therapy - Generic (FACT-G) Score |
|---|---|
| Description | The FACT-G is the sum of 4 sub-scales (physical, social, emotional and functional well-being) of FACT-Lym which includes total 27 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-108. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and "n" signified those participants who were evaluable for a specified time point. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 185 | 186 |
| Baseline |
79.86
(16.25)
|
80.78
(16.27)
|
| CFB at Cycle 3 Day 1 |
-1.87
(12.28)
|
0.11
(10.30)
|
| CFB at Cycle 4 Day 1 |
-9.37
(9.89)
|
0.52
(4.98)
|
| CFB at Cycle 5 Day 1 |
-2.44
(12.01)
|
0.06
(11.13)
|
| CFB at End of Induction Treatment |
-1.84
(13.83)
|
-0.92
(11.77)
|
| CFB at Follow-up Month 2 |
1.53
(13.42)
|
1.22
(12.01)
|
| CFB at Follow-up Month 4 |
2.55
(11.47)
|
3.06
(13.00)
|
| CFB at Follow-up Month 6 |
2.54
(10.68)
|
3.24
(11.40)
|
| CFB at Follow-up Month 8 |
-0.53
(10.15)
|
2.49
(11.45)
|
| CFB at Follow-up Month 10 |
2.29
(11.39)
|
3.46
(11.83)
|
| CFB at Follow-up Month 12 |
0.68
(13.16)
|
2.82
(14.29)
|
| CFB at Follow-up Month 14 |
2.48
(9.42)
|
2.94
(11.97)
|
| CFB at Follow-up Month 16 |
1.54
(10.61)
|
4.09
(12.87)
|
| CFB at Follow-up Month 18 |
1.16
(11.57)
|
4.06
(13.36)
|
| CFB at Follow-up Month 20 |
-1.21
(12.25)
|
3.05
(14.29)
|
| CFB at Follow-up Month 22 |
0.64
(14.27)
|
1.80
(12.43)
|
| CFB at Follow-up Month 24 |
-2.39
(9.32)
|
2.28
(13.83)
|
| CFB at Final Follow-up |
0.50
(11.25)
|
0.78
(14.94)
|
| CFB at Extension Follow Up Month 6 |
0.48
(8.71)
|
1.74
(14.23)
|
| CFB at Extension Follow Up Month 18 |
2.29
(8.40)
|
4.56
(15.02)
|
| CFB at Extension Follow Up Month 24 |
4.48
(11.10)
|
4.47
(15.22)
|
| Title | CFB in FACT-Lym Trial Outcome Index (TOI) |
|---|---|
| Description | TOI is the sum of 3 sub-scales (physical well-being, functional well-being, and Lymphoma sub-scale) of FACT-Lym which includes total 29 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-116. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 190 | 196 |
| Baseline |
84.66
(19.36)
|
84.76
(18.97)
|
| CFB at Cycle 3 Day 1 |
-1.94
(17.96)
|
1.81
(13.88)
|
| CFB at Cycle 4 Day 1 |
-10.40
(10.38)
|
26.44
(19.51)
|
| CFB at Cycle 5 Day 1 |
-1.38
(15.38)
|
2.37
(14.15)
|
| CFB at End of Induction Treatment |
-0.52
(17.23)
|
0.40
(16.45)
|
| CFB at Follow-up Month 2 |
3.75
(15.36)
|
4.60
(14.85)
|
| CFB at Follow-up Month 4 |
3.81
(13.39)
|
5.18
(17.06)
|
| CFB at Follow-up Month 6 |
3.26
(12.19)
|
6.07
(13.72)
|
| CFB at Follow-up Month 8 |
1.36
(12.39)
|
5.36
(14.21)
|
| CFB at Follow-up Month 10 |
3.52
(13.16)
|
4.94
(15.96)
|
| CFB at Follow-up Month 12 |
2.05
(15.14)
|
6.13
(15.72)
|
| CFB at Follow-up Month 14 |
2.25
(11.92)
|
5.13
(14.30)
|
| CFB at Follow-up Month 16 |
0.75
(14.15)
|
6.78
(15.11)
|
| CFB at Follow-up Month 18 |
1.36
(11.30)
|
7.26
(14.62)
|
| CFB at Follow-up Month 20 |
-0.64
(15.21)
|
6.36
(14.99)
|
| CFB at Follow-up Month 22 |
2.26
(14.54)
|
5.30
(17.88)
|
| CFB at Follow-up Month 24 |
-0.14
(13.44)
|
5.30
(17.88)
|
| CFB at Final Follow-up |
0.84
(14.80)
|
3.84
(16.22)
|
| CFB at Extension Follow Up Month 6 |
2.30
(10.77)
|
5.53
(18.44)
|
| CFB at Extension Follow Up Month 18 |
4.02
(14.01)
|
7.31
(15.69)
|
| CFB at Extension Follow Up Month 24 |
10.04
(13.35)
|
7.07
(17.59)
|
| Title | CFB in FACT-Lym Total Score |
|---|---|
| Description | FACT-Lym total score is the sum of physical well-being score (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and Lymphoma sub-scale (15 items); responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 186 | 187 |
| Baseline |
124.56
(24.17)
|
126.22
(23.98)
|
| CFB at Cycle 3 Day 1 |
-0.74
(17.91)
|
1.33
(13.89)
|
| CFB at Cycle 4 Day 1 |
-12.16
(14.80)
|
22.53
(16.23)
|
| CFB at Cycle 5 Day 1 |
-1.68
(16.61)
|
1.71
(15.23)
|
| CFB at End of Induction Treatment |
0.02
(18.55)
|
0.35
(18.29)
|
| CFB at Follow-up Month 2 |
5.10
(17.73)
|
3.54
(15.45)
|
| CFB at Follow-up Month 4 |
5.40
(16.29)
|
5.50
(17.76)
|
| CFB at Follow-up Month 6 |
5.03
(15.01)
|
6.57
(15.96)
|
| CFB at Follow-up Month 8 |
1.48
(14.27)
|
5.18
(15.61)
|
| CFB at Follow-up Month 10 |
4.58
(16.39)
|
5.70
(16.89)
|
| CFB at Follow-up Month 12 |
2.97
(17.84)
|
5.88
(18.93)
|
| CFB at Follow-up Month 14 |
3.18
(13.85)
|
5.92
(17.06)
|
| CFB at Follow-up Month 16 |
2.25
(14.98)
|
7.59
(16.97)
|
| CFB at Follow-up Month 18 |
2.16
(15.38)
|
6.99
(18.27)
|
| CFB at Follow-up Month 20 |
-0.89
(16.34)
|
5.66
(18.90)
|
| CFB at Follow-up Month 22 |
2.15
(19.03)
|
4.59
(17.98)
|
| CFB at Follow-up Month 24 |
-2.13
(15.74)
|
5.28
(18.75)
|
| CFB at Final follow-up |
2.15
(16.60)
|
2.55
(20.11)
|
| CFB at Extension Follow Up Month 6 |
1.22
(11.67)
|
5.14
(20.30)
|
| CFB at Extension Follow Up Month 18 |
4.92
(14.73)
|
6.88
(19.24)
|
| CFB at Extension Follow Up Month 24 |
9.69
(15.88)
|
6.13
(20.32)
|
| Title | Time to Deterioration of FACT-Lym TOI |
|---|---|
| Description | The median time, in month, from date of randomization until a clinically meaningful decline from baseline in TOI or death, whichever occurred first. TOI: sum of physical well-being score,functional well-being score, and Lymphoma sub-scale of FACT-Lym; total 29 items, responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-116. Higher scores indicate a better PRO/QoL. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from baseline. Time to deterioration was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley. In timeframe, follow-up months represents months after end of induction (EOI) (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). |
| Time Frame | Baseline up to approximately 8.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| Median (95% Confidence Interval) [Months] |
5.6
|
8.0
|
| Title | Percentage of Participants With Definitive Improvement (DI) From Baseline in FACT-Lym Instrument Scores |
|---|---|
| Description | FACT-Lym: 42-items in 5 subscales. Responses to each item range from 0 (Not at all) to 4 (Very much). FACT-Lym Lymphoma subscale includes 15 items (total score range = 0-60). FACT-Lym TOI is sum of 3 subscales (physical well-being, functional well-being, lymphoma subscale) and includes 29 items (total score range = 0-116). FACT-Lym total score is sum of 42 items (total score ranges from 0-168). For all above, higher scores indicate a better PRO/QoL. DI from baseline: at least 3 point increase from baseline in FACT-Lym Lymphoma subscale; at least 6 point increase from baseline in FACT Lym TOI; at least 7 point increase from baseline in FACT Lym total scores. In timeframe, follow-up months represents months after EOI (e.g. Follow-up Month 2 is 2 months after EOI; EOI = up to Month 6). |
| Time Frame | Baseline, Cycle 5 Day 1 (C5D1) (Cycle length = 28 days), Follow-up Months 6 (FUM6), 12 (FUM12), 18 (FUM18), 24 (FUM24), Extension Follow Up Month 6 (Extension FUM6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome. |
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine |
|---|---|---|
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). |
| Measure Participants | 209 | 204 |
| C5D1 (>=3 pt increase) |
30.3
14.5%
|
41.7
20.4%
|
| FUM6 (>=3 pt increase) |
37.9
18.1%
|
47.1
23.1%
|
| FUM12 (>=3 pt increase) |
36.7
17.6%
|
46.5
22.8%
|
| FUM18 (>=3 pt increase) |
35.6
17%
|
53.0
26%
|
| FUM24 (>=3 pt increase) |
35.3
16.9%
|
50
24.5%
|
| Ext FUM6 (>=3 pt increase) |
36.0
17.2%
|
57.8
28.3%
|
| C5D1 (>=6 pt increase) |
23.1
11.1%
|
34.4
16.9%
|
| FUM6 (>=6 pt increase) |
29.5
14.1%
|
43.7
21.4%
|
| FUM12 (>=6 pt increase) |
26.2
12.5%
|
47.0
23%
|
| FUM18 (>=6 pt increase) |
28.9
13.8%
|
51.8
25.4%
|
| FUM24 (>=6 pt increase) |
26.5
12.7%
|
48.0
23.5%
|
| Ext FUM6 (>=6 pt increase) |
44
21.1%
|
56.9
27.9%
|
| C5D1 (>=7 pt increase) |
24.4
11.7%
|
28.0
13.7%
|
| FUM6 (>=7 pt increase) |
34.1
16.3%
|
40.3
19.8%
|
| FUM12 (>=7 pt increase) |
31.1
14.9%
|
45.0
22.1%
|
| FUM18 (>=7 pt increase) |
31.1
14.9%
|
43.4
21.3%
|
| FUM24 (>=7 pt increase) |
20.6
9.9%
|
42.7
20.9%
|
| Ext FUM6 (>=7 pt increase) |
32
15.3%
|
47.7
23.4%
|
Adverse Events
| Time Frame | Baseline up to 8.5 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population included all participants who received any amount of obinutuzumab or bendamustine therapy. | |||
| Arm/Group Title | Bendamustine Alone | Obinutuzumab + Bendamustine | ||
| Arm/Group Description | Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles. | Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first). | ||
All Cause Mortality |
||||
| Bendamustine Alone | Obinutuzumab + Bendamustine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Bendamustine Alone | Obinutuzumab + Bendamustine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 76/203 (37.4%) | 91/204 (44.6%) | ||
| Blood and lymphatic system disorders | ||||
| AGRANULOCYTOSIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| ANAEMIA | 3/203 (1.5%) | 3 | 3/204 (1.5%) | 3 |
| FEBRILE NEUTROPENIA | 6/203 (3%) | 6 | 11/204 (5.4%) | 17 |
| LEUKOPENIA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| NEUTROPENIA | 1/203 (0.5%) | 1 | 6/204 (2.9%) | 6 |
| THROMBOCYTOPENIA | 0/203 (0%) | 0 | 5/204 (2.5%) | 5 |
| Cardiac disorders | ||||
| ATRIAL FIBRILLATION | 1/203 (0.5%) | 2 | 2/204 (1%) | 2 |
| ATRIAL FLUTTER | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| CARDIAC FAILURE | 0/203 (0%) | 0 | 2/204 (1%) | 3 |
| CORONARY ARTERY DISEASE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| MYOCARDIAL INFARCTION | 1/203 (0.5%) | 1 | 1/204 (0.5%) | 2 |
| PAROXYSMAL ARRHYTHMIA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| HYDROCELE | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Eye disorders | ||||
| NECROTISING RETINITIS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN UPPER | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| ANAL FISSURE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| COLITIS | 0/203 (0%) | 0 | 2/204 (1%) | 2 |
| DIARRHOEA | 3/203 (1.5%) | 3 | 0/204 (0%) | 0 |
| FOOD POISONING | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| GASTROINTESTINAL HAEMORRHAGE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| HAEMATOCHEZIA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| INTESTINAL PERFORATION | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| LARGE INTESTINAL OBSTRUCTION | 1/203 (0.5%) | 2 | 0/204 (0%) | 0 |
| MELAENA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| NAUSEA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| PANCREATITIS | 0/203 (0%) | 0 | 2/204 (1%) | 2 |
| RECTAL HAEMORRHAGE | 0/203 (0%) | 0 | 2/204 (1%) | 2 |
| UPPER GASTROINTESTINAL HAEMORRHAGE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| VOMITING | 1/203 (0.5%) | 1 | 2/204 (1%) | 2 |
| General disorders | ||||
| CATHETER SITE PAIN | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| CHEST PAIN | 2/203 (1%) | 2 | 1/204 (0.5%) | 1 |
| FATIGUE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| GENERAL PHYSICAL HEALTH DETERIORATION | 0/203 (0%) | 0 | 3/204 (1.5%) | 4 |
| HYPERTHERMIA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| INFLUENZA LIKE ILLNESS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| MALAISE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| PYREXIA | 3/203 (1.5%) | 3 | 6/204 (2.9%) | 7 |
| Hepatobiliary disorders | ||||
| CHOLECYSTITIS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Immune system disorders | ||||
| GRAFT VERSUS HOST DISEASE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| Infections and infestations | ||||
| ATYPICAL PNEUMONIA | 1/203 (0.5%) | 1 | 1/204 (0.5%) | 1 |
| BACTERAEMIA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| BRONCHITIS | 3/203 (1.5%) | 3 | 1/204 (0.5%) | 1 |
| CAMPYLOBACTER INFECTION | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| COXSACKIE MYOCARDITIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| DEVICE RELATED SEPSIS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| ENCEPHALITIS VIRAL | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| ENDOCARDITIS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| ERYSIPELAS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| ESCHERICHIA SEPSIS | 0/203 (0%) | 0 | 2/204 (1%) | 2 |
| FUNGAL SEPSIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| GASTROENTERITIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| GASTROENTERITIS NOROVIRUS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| HEPATITIS B REACTIVATION | 1/203 (0.5%) | 1 | 1/204 (0.5%) | 1 |
| HERPES ZOSTER | 3/203 (1.5%) | 3 | 1/204 (0.5%) | 1 |
| INFECTION | 2/203 (1%) | 2 | 0/204 (0%) | 0 |
| LOWER RESPIRATORY TRACT INFECTION | 1/203 (0.5%) | 5 | 3/204 (1.5%) | 3 |
| LUNG INFECTION | 1/203 (0.5%) | 1 | 2/204 (1%) | 2 |
| LUNG INFECTION PSEUDOMONAL | 1/203 (0.5%) | 2 | 0/204 (0%) | 0 |
| NEUTROPENIC SEPSIS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| PNEUMOCYSTIS JIROVECII PNEUMONIA | 2/203 (1%) | 2 | 1/204 (0.5%) | 1 |
| PNEUMONIA | 12/203 (5.9%) | 12 | 7/204 (3.4%) | 7 |
| PNEUMONIA CYTOMEGALOVIRAL | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| PSEUDOMONAL SEPSIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| PSEUDOMONAS BRONCHITIS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| RESPIRATORY SYNCYTIAL VIRUS INFECTION | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| RESPIRATORY TRACT INFECTION | 0/203 (0%) | 0 | 1/204 (0.5%) | 2 |
| SEPSIS | 7/203 (3.4%) | 7 | 6/204 (2.9%) | 6 |
| SEPTIC SHOCK | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| SINUSITIS | 1/203 (0.5%) | 1 | 2/204 (1%) | 2 |
| STAPHYLOCOCCAL SEPSIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| TOOTH INFECTION | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| UPPER RESPIRATORY TRACT INFECTION | 1/203 (0.5%) | 1 | 2/204 (1%) | 2 |
| URINARY TRACT INFECTION | 0/203 (0%) | 0 | 3/204 (1.5%) | 3 |
| UROSEPSIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| VASCULAR DEVICE INFECTION | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| Injury, poisoning and procedural complications | ||||
| FEMUR FRACTURE | 0/203 (0%) | 0 | 2/204 (1%) | 2 |
| HEAD INJURY | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| HIP FRACTURE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| INFUSION RELATED REACTION | 3/203 (1.5%) | 3 | 7/204 (3.4%) | 7 |
| JAW FRACTURE | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| POST PROCEDURAL BILE LEAK | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| SEROMA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| STAB WOUND | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| VASCULAR PSEUDOANEURYSM | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| WRIST FRACTURE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| Investigations | ||||
| BLOOD CREATININE INCREASED | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| BORRELIA TEST | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| DEHYDRATION | 2/203 (1%) | 2 | 1/204 (0.5%) | 1 |
| HYPERGLYCAEMIA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| HYPOKALAEMIA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| TUMOUR LYSIS SYNDROME | 2/203 (1%) | 2 | 0/204 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| MUSCLE HAEMORRHAGE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| OSTEOARTHRITIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| ACUTE MYELOID LEUKAEMIA | 2/203 (1%) | 2 | 1/204 (0.5%) | 1 |
| ADENOCARCINOMA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| ADENOCARCINOMA GASTRIC | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| BASAL CELL CARCINOMA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| BLADDER CANCER | 0/203 (0%) | 0 | 2/204 (1%) | 2 |
| BREAST CANCER | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| BRONCHIAL NEOPLASM | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| CHOLANGIOCARCINOMA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| COLORECTAL CANCER | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| INTESTINAL ADENOCARCINOMA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| LEIOMYOSARCOMA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| LEUKAEMIA | 2/203 (1%) | 2 | 0/204 (0%) | 0 |
| LUNG NEOPLASM MALIGNANT | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| MALIGNANT MELANOMA | 1/203 (0.5%) | 1 | 2/204 (1%) | 2 |
| MYELODYSPLASTIC SYNDROME | 1/203 (0.5%) | 1 | 3/204 (1.5%) | 3 |
| POLYCYTHAEMIA VERA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| RENAL CANCER | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| SQUAMOUS CELL CARCINOMA | 3/203 (1.5%) | 3 | 0/204 (0%) | 0 |
| T-CELL LYMPHOMA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| THYROID NEOPLASM | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Nervous system disorders | ||||
| AMYOTROPHIC LATERAL SCLEROSIS | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| CENTRAL NERVOUS SYSTEM LESION | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| HEADACHE | 1/203 (0.5%) | 1 | 1/204 (0.5%) | 1 |
| ISCHAEMIC STROKE | 2/203 (1%) | 2 | 0/204 (0%) | 0 |
| POST HERPETIC NEURALGIA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| PRESYNCOPE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| SUBARACHNOID HAEMORRHAGE | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| SYNCOPE | 0/203 (0%) | 0 | 2/204 (1%) | 2 |
| Psychiatric disorders | ||||
| ANXIETY | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| MANIA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| Renal and urinary disorders | ||||
| DYSURIA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| END STAGE RENAL DISEASE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| HAEMATURIA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| POLLAKIURIA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| URETERIC OBSTRUCTION | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| URINARY INCONTINENCE | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| Reproductive system and breast disorders | ||||
| BENIGN PROSTATIC HYPERPLASIA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| BRONCHOSPASM | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| CHYLOTHORAX | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| EMPHYSEMA | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| HYPOXIA | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| PLEURAL EFFUSION | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| PNEUMONIA ASPIRATION | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| PNEUMOTHORAX | 0/203 (0%) | 0 | 1/204 (0.5%) | 1 |
| PULMONARY EMBOLISM | 3/203 (1.5%) | 3 | 1/204 (0.5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| PARANEOPLASTIC PEMPHIGUS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Social circumstances | ||||
| SOCIAL PROBLEM | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| Vascular disorders | ||||
| CIRCULATORY COLLAPSE | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| DEEP VEIN THROMBOSIS | 1/203 (0.5%) | 1 | 0/204 (0%) | 0 |
| HYPOTENSION | 2/203 (1%) | 2 | 2/204 (1%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| Bendamustine Alone | Obinutuzumab + Bendamustine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 194/203 (95.6%) | 200/204 (98%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 34/203 (16.7%) | 41 | 23/204 (11.3%) | 36 |
| NEUTROPENIA | 59/203 (29.1%) | 103 | 74/204 (36.3%) | 150 |
| THROMBOCYTOPENIA | 50/203 (24.6%) | 101 | 26/204 (12.7%) | 54 |
| Gastrointestinal disorders | ||||
| ABDOMINAL DISTENSION | 11/203 (5.4%) | 12 | 6/204 (2.9%) | 6 |
| ABDOMINAL PAIN | 20/203 (9.9%) | 23 | 16/204 (7.8%) | 18 |
| ABDOMINAL PAIN UPPER | 15/203 (7.4%) | 19 | 11/204 (5.4%) | 12 |
| CONSTIPATION | 40/203 (19.7%) | 55 | 42/204 (20.6%) | 56 |
| DIARRHOEA | 61/203 (30%) | 83 | 57/204 (27.9%) | 81 |
| DRY MOUTH | 12/203 (5.9%) | 15 | 8/204 (3.9%) | 8 |
| DYSPEPSIA | 9/203 (4.4%) | 11 | 13/204 (6.4%) | 16 |
| NAUSEA | 123/203 (60.6%) | 227 | 107/204 (52.5%) | 210 |
| VOMITING | 54/203 (26.6%) | 87 | 44/204 (21.6%) | 67 |
| General disorders | ||||
| ASTHENIA | 25/203 (12.3%) | 35 | 31/204 (15.2%) | 44 |
| CHEST PAIN | 4/203 (2%) | 4 | 11/204 (5.4%) | 11 |
| CHILLS | 21/203 (10.3%) | 24 | 28/204 (13.7%) | 30 |
| FATIGUE | 67/203 (33%) | 114 | 81/204 (39.7%) | 151 |
| INFLUENZA LIKE ILLNESS | 9/203 (4.4%) | 10 | 11/204 (5.4%) | 12 |
| MUCOSAL INFLAMMATION | 8/203 (3.9%) | 11 | 11/204 (5.4%) | 12 |
| OEDEMA PERIPHERAL | 14/203 (6.9%) | 17 | 15/204 (7.4%) | 16 |
| PYREXIA | 36/203 (17.7%) | 44 | 54/204 (26.5%) | 80 |
| Infections and infestations | ||||
| BRONCHITIS | 18/203 (8.9%) | 23 | 24/204 (11.8%) | 36 |
| HERPES ZOSTER | 14/203 (6.9%) | 16 | 10/204 (4.9%) | 10 |
| NASOPHARYNGITIS | 8/203 (3.9%) | 10 | 22/204 (10.8%) | 27 |
| RHINITIS | 8/203 (3.9%) | 9 | 12/204 (5.9%) | 13 |
| SINUSITIS | 11/203 (5.4%) | 14 | 24/204 (11.8%) | 35 |
| UPPER RESPIRATORY TRACT INFECTION | 17/203 (8.4%) | 21 | 26/204 (12.7%) | 34 |
| URINARY TRACT INFECTION | 12/203 (5.9%) | 14 | 23/204 (11.3%) | 36 |
| Injury, poisoning and procedural complications | ||||
| INFUSION RELATED REACTION | 115/203 (56.7%) | 242 | 125/204 (61.3%) | 283 |
| Investigations | ||||
| WEIGHT DECREASED | 18/203 (8.9%) | 18 | 11/204 (5.4%) | 11 |
| Metabolism and nutrition disorders | ||||
| DECREASED APPETITE | 37/203 (18.2%) | 49 | 37/204 (18.1%) | 40 |
| HYPOKALAEMIA | 15/203 (7.4%) | 21 | 15/204 (7.4%) | 22 |
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRALGIA | 11/203 (5.4%) | 12 | 24/204 (11.8%) | 31 |
| BACK PAIN | 18/203 (8.9%) | 22 | 17/204 (8.3%) | 19 |
| MYALGIA | 15/203 (7.4%) | 17 | 13/204 (6.4%) | 14 |
| PAIN IN EXTREMITY | 10/203 (4.9%) | 13 | 22/204 (10.8%) | 27 |
| Nervous system disorders | ||||
| DIZZINESS | 17/203 (8.4%) | 23 | 14/204 (6.9%) | 22 |
| DYSGEUSIA | 16/203 (7.9%) | 20 | 15/204 (7.4%) | 20 |
| HEADACHE | 32/203 (15.8%) | 37 | 27/204 (13.2%) | 36 |
| Psychiatric disorders | ||||
| INSOMNIA | 21/203 (10.3%) | 26 | 21/204 (10.3%) | 24 |
| Respiratory, thoracic and mediastinal disorders | ||||
| COUGH | 40/203 (19.7%) | 46 | 64/204 (31.4%) | 85 |
| DYSPNOEA | 23/203 (11.3%) | 28 | 26/204 (12.7%) | 27 |
| NASAL CONGESTION | 5/203 (2.5%) | 6 | 17/204 (8.3%) | 18 |
| OROPHARYNGEAL PAIN | 7/203 (3.4%) | 7 | 12/204 (5.9%) | 15 |
| RHINORRHOEA | 3/203 (1.5%) | 3 | 11/204 (5.4%) | 11 |
| Skin and subcutaneous tissue disorders | ||||
| PRURITUS | 12/203 (5.9%) | 13 | 29/204 (14.2%) | 38 |
| RASH | 24/203 (11.8%) | 27 | 28/204 (13.7%) | 35 |
| Vascular disorders | ||||
| HYPOTENSION | 1/203 (0.5%) | 2 | 23/204 (11.3%) | 26 |
| PHLEBITIS | 13/203 (6.4%) | 14 | 11/204 (5.4%) | 11 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 | Genentech |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
- GAO4753g
- GO01297
- 2009-015504-25