A Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+RO5072759 (GA101) in Patients With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2009-015504-25-CZ
• Date of registration: 16/04/2010
• Prospective Registration: Yes
• Primary sponsor: GENENTECH, Inc
• Public title: A Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+RO5072759 (GA101) in Patients With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma
• 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 - GADOLIN
• Date of first enrolment: 04/06/2010
• Target sample size: 410
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-015504-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Trial Information Support Line,TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line,TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
– History of histologically documented, CD20+, indolent NHL
– Refractory to any previous regimen containing rituximab
– Previously treated with a maximum of four unique chemotherapy containing treatment regimens
– All patients must have at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 246
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 164

Exclusion criteria:
– Prior use of any monoclonal antibody (other than anti-CD20) within 3 months
– Chemotherapy or other investigational therapy within 28 days
– 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 (e.g., patients in whom re-dosing with rituximab would be contraindicated for safety reasons)
– History of sensitivity to mannitol
– Central nervous system lymphoma, prior DLBCL, or histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
– History of other malignancy that could affect compliance with the protocol or interpretation of results
– Patients with a history of confirmed PML
– 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
– 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 or Hepatitis C
– Known history of 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
– Agreement to use an effective form of contraception for the duration of the study
– Ongoing corticosteroid use >30 mg/day prednisone or equivalent
– Radiation therapy within 42 days prior to the start of cycle 1


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

CD20+, indolent NHL
MedDRA version: 20.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: GA101
Product Code: RO 5072759/F06
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 949142-50-1
Current Sponsor code: RO5072759
Other descriptive name: GA101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Product Code: RO5469113
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Bendamustine hydrochloride
CAS Number: 3543-75-7
Current Sponsor code: RO5469113
Other descriptive name: n/a
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 220-

Primary Outcome(s)

Secondary Objective: •To compare PFS as assessed by the investigator
•To compare OS between study arms
•To evaluate in each study arm and compare between study arms the following: overall response rate and CRR at the Study Treatment Completion/Early Study Treatment Termination Visit; best ORR achieved during treatment or within 12 months of the start of treatment; disease-free survival in CR patients; duration of response in patients with CR and PR
•To compare event-free survival between the two study arms
•To evaluate and compare the safety profiles of patients treated with the combination of GA101 + bendamustine and bendamustine alone
•To characterize the pharmacokinetics of GA101 in combination with bendamustine and evaluate for drug-drug interactions by comparing the pharmacokinetics of the combination with the pharmacokinetics of bendamustine alone
•To analyze pharmacoeconomics (medical resource utilization) in both arms of the study
•To assess patient-reported outcomes in both treatment arms

Primary end point(s): 1. Progression-free survival

Main Objective: To evaluate clinical benefit in terms of PFS, as assessed by an IRF, for GA101 when used in combination with bendamustine compared with bendamustine alone in patients with indolent NHL refractory to prior rituximab-containing therapy

Timepoint(s) of evaluation of this end point: 1. Time from randomization to first occurrence of progression or relapse, as assessed by the IRF, or death from any cause.

Secondary Outcome(s)

Secondary end point(s): 1. Overall survival
2. Complete response (CR) and overall response (CR or partial response [PR])
3. Best response
4. PFS as assessed by Investigator

Timepoint(s) of evaluation of this end point: 1. Time from randomization to death
2. At 6 months
3. Up to 12 months after start of treatment
4. Prior to cycle 4, approximately 28-42 days after cycle 6, every 2 months (3 months for CT scans) for 24 months after the first 6 months of treatment, and every 6 months thereafter for an additional 2 years or until progression

Secondary ID(s)

GAO4753g

Source(s) of Monetary Support

Genentech Inc. c/o F. Hoffmann-La Roche Ltd.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 12/10/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-015504-25/results