Phase 3
Completed N=413
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)
Source: ClinicalTrials.gov NCT01059630 ↗Enrolled (actual)
413
Serious AEs
41.0%
Results posted
Nov 2016
Primary outcomePrimary: Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death — 125; 87 participants
◆ Published Evidence
Highly cited
343citations · ~34 / year
Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial.
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).
Linked Publications (4)
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Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial.
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Overall Survival Benefit in Patients With Rituximab-Refractory Indolent Non-Hodgkin Lymphoma Who Received Obinutuzumab Plus Bendamustine Induction and Obinutuzumab Maintenance in the GADOLIN Study.
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MRD response in relapsed/refractory FL after obinutuzumab plus bendamustine or bendamustine alone in the GADOLIN trial.
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Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death |
125; 87 | — |
| PRIMARY Progression-Free Survival (PFS) as Assessed by IRC |
14.1; 29.2 | <0.0001 sig |
| SECONDARY Number of Participants With PD or Death as Assessed by Investigator |
152; 132 | — |
| SECONDARY PFS as Assessed by Investigator |
14.1; 25.8 | <0.0001 sig |
| SECONDARY Percentage of Participants With Objective Response as Assessed by IRC |
77.5; 75.5 | 0.9298 |
| SECONDARY Percentage of Participants With Objective Response as Assessed by Investigator |
83.3; 82.4 | 0.7857 |
| SECONDARY Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC |
17.2; 16.2; 60.3; 59.3; 12.0; 13.7 | — |
| SECONDARY Percentage of Participants With Best Overall Response (BOR) as Assessed by Investigator |
21.5; 23.5; 61.7; 58.8; 6.7; 6.4 | — |
| SECONDARY Percentage of Participants With BOR at the End of Induction Treatment as Assessed by IRC |
12.0; 11.8; 52.4; 54.9; 10.1; 11.8 | — |
| SECONDARY Percentage of Participants With BOR at the End of Induction Treatment as Assessed by Investigator |
15.8; 17.2; 53.1; 60.3; 4.3; 3.9 | — |
| SECONDARY Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC |
64.4; 66.7 | 0.8347 |
| SECONDARY Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by Investigator |
68.9; 77.5 | 0.0466 sig |
| SECONDARY Duration of Response (DoR) as Assessed by IRC |
12.7; 38.5 | — |
| SECONDARY Duration of Response (DoR) as Assessed by Investigator |
12.7; 32.3 | — |
| SECONDARY Disease-Free Survival (DFS) in Participants With CR as Assessed by IRC |
13.2; NA | — |
| SECONDARY Disease-Free Survival (DFS) in Participants With CR as Assessed by Investigator |
20.0; 36.0 | — |
| SECONDARY Event-free Survival (EFS) as Assessed by IRC |
13.7; 25.3 | 0.0001 sig |
| SECONDARY Percentage of Participants Who Died |
49.3; 41.2 | — |
| SECONDARY Overall Survival (OS) |
65.6; 88.3 | 0.0810 |
| SECONDARY Change From Baseline (CFB) in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)-Physical Well Being Sub-scale Score |
22.58; 22.76; -1.56; -0.69; -6.80; -3.00 | — |
| SECONDARY CFB in FACT-Lym-Social/Family Well-being Sub-scale Score |
22.04; 22.14; -0.21; -0.10; -1.00; 3.11 | — |
| SECONDARY CFB in FACT-Lym-Emotional Well-Being Sub-scale Score |
17.38; 17.81; 0.61; 0.78; -0.60; 3.40 | — |
| SECONDARY CFB in FACT-Lym-Functional Well-Being Sub-scale Score |
17.98; 17.90; -0.54; 0.38; -0.80; 1.78 | — |
| SECONDARY CFB in FACT-Lym-Lymphoma Sub-scale Score |
44.79; 45.61; 0.98; 1.24; -2.80; 9.50 | — |
| SECONDARY CFB in Euro Quality of Life 5 Dimension (EuroQoL-5D/EQ-5D) - Health State Profile Utility Score During Induction Phase |
0.77; 0.79; 0.03; 0.00; -0.10; -0.07 | — |
| SECONDARY CFB in EuroQol 5D (EQ-5D) - Health State Profile Utility Score During Maintenance Phase |
-0.15; 0.15; 0.03; 0.15; 0.04; 0.15 | — |
| SECONDARY CFB in EQ-5D Visual Analogue Scale (VAS) Score During Induction Phase |
69.48; 68.03; 0.91; 3.32; -14.00; -4.33 | — |
| SECONDARY CFB in EQ-5D VAS Score During Maintenance Phase |
-40.00; 5.00; 5.59; 5.00; 6.04; 5.00 | — |
| SECONDARY CFB in Functional Assessment of Cancer Therapy - Generic (FACT-G) Score |
79.86; 80.78; -1.87; 0.11; -9.37; 0.52 | — |
| SECONDARY CFB in FACT-Lym Trial Outcome Index (TOI) |
84.66; 84.76; -1.94; 1.81; -10.40; 26.44 | — |
| SECONDARY CFB in FACT-Lym Total Score |
124.56; 126.22; -0.74; 1.33; -12.16; 22.53 | — |
| SECONDARY Time to Deterioration of FACT-Lym TOI |
5.6; 8.0 | — |
| SECONDARY Percentage of Participants With Definitive Improvement (DI) From Baseline in FACT-Lym Instrument Scores |
30.3; 41.7; 37.9; 47.1; 36.7; 46.5 | — |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT01059630) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.