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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)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01059630
First Posted: February 1, 2010
Last Update Posted: September 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Genentech, Inc.
  Purpose
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).

Condition Intervention Phase
Non-Hodgkin's Lymphoma Drug: Obinutuzumab Drug: Bendamustine Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Randomized, Phase III Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+RO5072759 (GA101) in Patients With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death [ 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]) ]
    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 [ 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]) ]
    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 [ 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]) ]
    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 [ 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]) ]
    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 and Investigator [ 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 12 months overall) ]
    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 and Investigator [ 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 12 months overall) ]
    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 Objective Response at the End of Induction Treatment as Assessed by IRC and Investigator [ 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) ]
    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 BOR at the End of Induction Treatment as Assessed by IRC and Investigator [ 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) ]
    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).

  • Duration of Response (DoR) as Assessed by IRC [ 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]) ]
    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 [ 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]) ]
    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 [ 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]) ]
    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.

  • Percentage of Participants Who Died [ Time Frame: Baseline until death (up to 4.5 years overall) ]
  • Overall Survival (OS) [ Time Frame: Baseline until death (up to 4.5 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 [ Time Frame: Baseline, Day 1 of Cycles 1, 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 and 18 ]
    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 [ Time Frame: Baseline, Day 1 of Cycles 1, 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 and 18 ]
    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 [ Time Frame: Baseline, Day 1 of Cycles 1, 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 and 18 ]
    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 [ Time Frame: Baseline, Day 1 of Cycles 1, 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 and 18 ]
    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 [ Time Frame: Baseline, Day 1 of Cycles 1, 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 and 18 ]
    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 [ Time Frame: Baseline, Day 1 of Cycles 1, 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, and 4 ]
    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 [ 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) ]
    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 [ Time Frame: Baseline, Day 1 of Cycles 1, 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2 and 4 ]
    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 [ 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) ]
    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 [ Time Frame: Baseline, Day 1 of Cycles 1, 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 and 18 ]
    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) [ Time Frame: Baseline, Day 1 of Cycles 1, 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 and 18 ]
    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 [ Time Frame: Baseline, Day 1 of Cycles 1, 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 and 18 ]
    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 [ Time Frame: Baseline up to approximately 4 years (Baseline, Day 1 of Cycles 1, 3, 4, 5, EOI 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 EOI]; Extension follow-up Months 6 and 18) ]
    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 [ Time Frame: Baseline, Cycle 5 Day 1 (C5D1) (Cycle length = 28 days), Follow-up Months 6 (FUM6), and 12 (FUM12) ]
    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).


Enrollment: 396
Actual Study Start Date: April 30, 2010
Estimated Study Completion Date: February 19, 2019
Primary Completion Date: September 30, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: RO5072759; GA101
Drug: Bendamustine
IV infusion.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01059630


  Hide Study Locations
Locations
United States, Alabama
Southern Cancer Center, PC
Mobile, Alabama, United States, 36608
United States, Arizona
Dr. Donald W. Hill, MD, FACP
Casa Grande, Arizona, United States, 85122
United States, Arkansas
Highlands Oncology Group
Rogers, Arkansas, United States, 72758
United States, California
Kaiser Permanente - Bellflower
Bellflower, California, United States, 90706
Bay Area Cancer Research Group, LLC
Pleasant Hill, California, United States, 94523
Sharp Memorial Hospital
San Diego, California, United States, 92123
United States, District of Columbia
Georgetown University Medical Center Lombardi Cancer Center
Washington, D.C., District of Columbia, United States, 20057
Washington DC VA Med Center; Hematology
Washington, D.C., District of Columbia, United States, 20422
United States, Florida
University of Florida
Gainesville, Florida, United States, 32607
University of Florida; Division of Hematology/Oncology
Gainesville, Florida, United States, 33610-0277
Md Anderson Cancer Center Orlando
Orlando, Florida, United States, 32806
United States, Illinois
Rush Cancer Institute
Chicago, Illinois, United States, 60612
Quincy Medical Group
Quincy, Illinois, United States, 62301
Simmons Cancer Institute
Springfield, Illinois, United States, 62794-9677
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kentucky
Univ Louisville School of Med
Louisville, Kentucky, United States, 40202
United States, Maine
New England Cancer Specialists
Scarborough, Maine, United States, 04074
United States, Maryland
Meritus Center for Clinical Research
Hagerstown, Maryland, United States, 21740
United States, Missouri
Capitol Comprehensive CA Care
Jefferson City, Missouri, United States, 65101
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Hematology Oncology Assoc SJ
Mount Holly, New Jersey, United States, 08060
United States, New Mexico
San Juan Oncology
Farmington, New Mexico, United States, 87401
United States, Ohio
The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.
Columbus, Ohio, United States, 43219
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97210
Pacific Oncology, PC
Portland, Oregon, United States, 97210
OHSU Ctr for Health & Healing
Portland, Oregon, United States, 97239
United States, Pennsylvania
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
United States, South Dakota
Sanford Health System
Sioux Falls, South Dakota, United States, 57105
United States, Texas
South Texas Inst of Cancer
Corpus Christi, Texas, United States, 78405
University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
United States, Wisconsin
Univ of Wisconsin Hosp & Clin
Madison, Wisconsin, United States, 53792
Austria
Lkh-Univ. Klinikum Graz
Graz, Austria, 8036
Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
Salzburg, Austria, 5020
Medizinische Universität Wien
Wien, Austria, 1090
Belgium
ZNA Stuivenberg
Antwerpen, Belgium, 2060
AZ Groeninge (Loofstraat)
Kortrijk, Belgium, 8500
CHU Ambroise Paré
Mons, Belgium, 7000
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
British Columbia Cancer Agency
Kelowna, British Columbia, Canada, V1Y 5L3
British Columbia Cancer Agency
Vancouver, British Columbia, Canada, V5Z 1H6
Canada, Manitoba
Manitoba Cancer Care
Winnipeg, Manitoba, Canada, R3E0V9
Canada, New Brunswick
Moncton Hospital
Moncton, New Brunswick, Canada, E1C 6Z8
Canada, Ontario
Toronto East General Hospital; Main Pharmacy G Wing Basement
East York, Ontario, Canada, M4C 3E7
Princess Margaret Hospital
Toronto, Ontario, Canada, M4X 1K9
Canada, Quebec
Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
Montreal, Quebec, Canada, H3T 1E2
CHA Hopital de I enfant-Jesus
Quebec City, Quebec, Canada, G1J 1Z4
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Czechia
Fakultni nemocnice Brno; Interni hematoonkologicka klinika
Brno, Czechia, 625 00
Fakultni nemocnice Hradec Kralove
Hradec Kralove, Czechia, 500 05
I Interni klinika; Vseobecna fakultni nemocnice
Prague 2, Czechia, 128 08
France
Institut Bergonie; Hematologie Oncologie
Bordeaux, France, 33076
Polyclinique Bordeaux Nord
Bordeaux, France, 33300
Hopital Henri Mondor
Creteil, France, 94010
CH Dijon
Dijon, France, 21079
Centre d'oncologie-radiotherap
LeMans, France, 72015
Hopital Claude Huriez
Lille, France, 59037
Centre Leon Berard
Lyon, France, 69008
Hopital Bon Secour
Metz, France, 57038
CHU Hopital Saint Eloi
Montpellier, France, 34295
Hopital Hotel Dieu Et Hme; Clinique Dermatologique
Nantes, France, 44093
Hopital Saint Louis; Dermatologie 1
Paris, France, 75475
Hopital Necker
Paris, France, 75743
CHU Bordeaux
Pessac, France, 33604
Centre Hospitalier Lyon Sud; Hematolgie
Pierre Benite, France, 69495
Chu De Poitiers; Chu La Miletrie
Poitiers, France, 86021
CHU de Reims
Reims, France, 51100
Hopital Pontchaillou
Rennes, France, 35033
Centre Henri Becquerel
Rouen, France, 76038
Clinique Ste Anne
Strasbourg, France, 67000
CHRU de; Maladies, Vasculaires
Vandoeuvre, France, 54511
Germany
St. Johannes Hospital Duisburg
Duisburg, Germany, 47166
Klinikum Frankfurt Höchst
Frankfurt am Main, Germany, 65929
Asklepios Klinik St. Georg
Hamburg, Germany, 20099
Universitaetsklinikum Leipzig
Leipzig, Germany, 04103
Klinikum Grosshadern der LMU
Muenchen, Germany, 81377
Schwarzwald-Baar Klinikum GmbH
Villingen-Schwenningen, Germany, 78052
Italy
Azienda Ospedaliera Universitaria di Modena
Modena, Emilia-Romagna, Italy, 41100
Azienda Ospedaliera Univ, Ematologica
Udine, Friuli-Venezia Giulia, Italy, 33100
Azienda Ospedaliera Univ
Roma, Lazio, Italy, 00133
Universita La Sapienza
Roma, Lazio, Italy, 00161
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
Milano, Lombardia, Italy, 20133
Irccs Policlinico San Matteo; Divisione Di Ematologia
Pavia, Lombardia, Italy, 27100
Azienda Ospedale San Giovanni
Torino, Piemonte, Italy, 10126
Ospedale Mauriziano Umberto I
Torino, Piemonte, Italy, 10128
Azienda Ospedaliero Univ
Bari, Puglia, Italy, 70124
Ospedale Vito Fazzi
Lecce, Puglia, Italy, 73100
Azienda Ospedaliero Univ
Catania, Sicilia, Italy, 95124
Azienda Ospedaliera Univ
Firenze, Toscana, Italy, 50141
Netherlands
VU MEDISCH CENTRUM; Dept. of Medical Oncology
Amsterdam, Netherlands, 1081 HV
Haga Ziekenhuis
Den Haag, Netherlands, 2504 LN
Albert Schweitzer Ziekenhuis
Dordrecht, Netherlands, 3371 NM
Universitair Medisch Centrum Groningen
Groningen, Netherlands, 9700 RB
Erasmus MC
Rotterdam, Netherlands, 3000 CA
Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology
Rotterdam, Netherlands, 3075 EA
Russian Federation
Regional Oncology Hospital
Irkutsk, Russian Federation, 664035
Blokhin Cancer Research Center; Combined Treatment
Moscow, Russian Federation, 115478
City Clin Hosp n.a. S.P.Botkin
Moscow, Russian Federation, 125101
Russian Hema Res Ctr of RAMS
Moscow, Russian Federation, 125167
Republican Clinical Hospital n.a. Baranov; Haematology
Petrozavodsk, Russian Federation, 185019
Ryazan Regional Clinical Hosp
Ryazan, Russian Federation, 390039
St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta
Saint-Petersburg, Russian Federation, 197022
SRI of Hematology and Transfusiology
St. Petersburg, Russian Federation, 191024
Spain
Clinica Universitaria de Navarra
Pamplona, Navarra, Spain, 31008
Hospital Univ. Nuestra Señora de Valme;
Sevillac, Sevilla, Spain, 41014
Hospital Universitario Basurto
Bilbao, Vizcaya, Spain, 48013
Hospital Universitario de la Princesa; Servicio de Hematologia
Madrid, Spain, 28006
Hospital Universitario La Paz
Madrid, Spain, 28034
Hospital Universitario Miguel Servet
Zaragoza, Spain, 50009
Sweden
Skånes University Hospital, Skånes Department of Onclology
Lund, Sweden, 22185
Hematology Center; Karolinska Univ Hosp
Stockholm, Sweden, 14186
Norrlands Uni Hospital; Onkologi Avd.
Umea, Sweden, 90185
Onc Clin, Akademiska Sjukhuset
Uppsala, Sweden, 75185
Switzerland
Universitaetsspital Basel; Onkologie
Basel, Switzerland, 4031
Inselspital Bern; Medizinische Onkologie
Bern, Switzerland, 3010
Kantonsspital Graubünden;Onkologie und Hämatologie
Chur, Switzerland, 7000
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom, G12 0YN
Leicester Royal Infirmary
Leicester, United Kingdom, LE1 5WW
Barts & London School of Med; Medical Oncology
London, United Kingdom, EC1A 7BE
Freeman Hospital
Newcastle upon Tyne, United Kingdom, NE7 7DN
Singleton Hospital; Pharmacy Department
Swansea, United Kingdom, SA2 8QA
Sponsors and Collaborators
Genentech, Inc.
Roche Pharma AG
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01059630     History of Changes
Other Study ID Numbers: GAO4753g
GO01297 ( Other Identifier: Hoffmann-La Roche )
First Submitted: January 28, 2010
First Posted: February 1, 2010
Results First Submitted: September 27, 2016
Results First Posted: November 17, 2016
Last Update Posted: September 12, 2017
Last Verified: September 2017

Keywords provided by Genentech, Inc.:
follicular
follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Obinutuzumab
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action