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)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01059630
• Date of registration: 28/01/2010
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc.
• Public title: 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)
• Scientific 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
• Date of first enrolment: April 30, 2010
• Target sample size: 413
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01059630
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, Czechia, France, Germany, Italy, Netherlands, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Genentech, Inc.

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-Hodgkin's Lymphoma

Intervention(s)

Drug: Bendamustine

Drug: Obinutuzumab

Primary Outcome(s)

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])]

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])]

Secondary Outcome(s)

CFB in FACT-Lym-Lymphoma Sub-scale Score [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]

CFB in FACT-Lym-Emotional Well-Being Sub-scale Score [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]

Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by 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)]

Duration of Response (DoR) as Assessed by IRC [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 5 years)]

PFS as Assessed by Investigator [Time Frame: Baseline until PD or death, whichever occurred first (up to 8.5 years overall)]

Event-free Survival (EFS) as Assessed by IRC [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 5 years)]

CFB in Functional Assessment of Cancer Therapy - Generic (FACT-G) Score [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]

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)]

Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 5 years)]

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), 12 (FUM12), 18 (FUM18), 24 (FUM24), Extension Follow Up Month 6 (Extension FUM6)]

CFB in FACT-Lym-Functional Well-Being Sub-scale Score [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]

CFB in FACT-Lym Trial Outcome Index (TOI) [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]

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)]

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 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]

Disease-Free Survival (DFS) in Participants With CR as Assessed by IRC [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 5 years)]

Disease-Free Survival (DFS) in Participants With CR as Assessed by Investigator [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)]

Percentage of Participants With BOR at the End of Induction Treatment as Assessed by 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)]

CFB in EQ-5D Visual Analogue Scale (VAS) Score During Induction Phase [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]

Percentage of Participants With Best Overall Response (BOR) as Assessed by Investigator [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)]

Percentage of Participants With Objective Response as Assessed by IRC [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 5 years)]

Number of Participants With PD or Death as Assessed by Investigator [Time Frame: Baseline until PD or death, whichever occurred first (up to 8.5 years overall))]

Overall Survival (OS) [Time Frame: Baseline until death (up to 8.5 years overall)]

Percentage of Participants With BOR at the End of Induction Treatment as Assessed by IRC [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)]

CFB in FACT-Lym-Social/Family Well-being Sub-scale Score [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]

Duration of Response (DoR) as Assessed by Investigator [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)]

Percentage of Participants With Objective Response as Assessed by Investigator [Time Frame: Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)]

Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC [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)]

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 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4 and 14]

CFB in FACT-Lym Total Score [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]

Time to Deterioration of FACT-Lym TOI [Time Frame: Baseline up to approximately 8.5 years]

Percentage of Participants Who Died [Time Frame: Baseline until death (up to 8.5 years overall)]

Secondary ID(s)

GAO4753g

GO01297

2009-015504-25

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Roche Pharma AG

Results

• Results available: Yes
• Date Posted: 17/11/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01059630