Overview

This trial is active, not recruiting.

Condition non-hodgkin's lymphoma
Treatments ro5072759, chemotherapy, rituximab [mabthera/rituxan]
Phase phase 3
Target CD20
Sponsor Hoffmann-La Roche
Collaborator German Low Grade Lymphoma Study Group
Start date July 2011
End date February 2017
Trial size 1401 participants
Trial identifier NCT01332968, BO21223

Summary

This open-label, randomized study will assess the efficacy and safety of obinutuzumab (RO5072759) in combination with chemotherapy compared to MabThera/Rituxan (rituximab) with chemotherapy followed by obinutuzumab or MabThera/Rituxan maintenance in patients with untreated advanced indolent non-Hodgkin's lymphoma. After the end of the induction period, patients achieving response (CR or PR) will go on to a maintenance period thereby continuing on their randomized antibody treatment alone every 2 months until disease progression for a total of 2 years. Anticipated time on study treatment is up to approximately 2.5 years. After maintenance or observation patients will be followed for 5 years until progression. After progression, patients will be followed for new anti-lymphoma therapy and overall survival until the end of the study.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
chemotherapy
CHOP (6 cycles of 21 days), CVP (8 cycles of 21 days), Bendamustine (6 cycles of 28 days). Patients with follicular lymphoma are receiving either CHOP, CVP or Bendamustine as background chemotherapy as selected by each participating site at study start. Background chemotherapy for patients with non-follicular lymphoma will be chosen by the site individually for each patient.
rituximab [mabthera/rituxan]
375 mg/m2 iv on Day 1 of Cycles 1-8 (21-day cycles) or Cycles 1-6 (28-day cycles); followed by 375 mg/m2 iv every 2 months in responders until disease progression, for up to 2 years
(Experimental)
ro5072759 GA101
1000 mg iv on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-8 (21-day cycles) or Cycles 2-6 (28-day cycles); followed by 1000 mg iv every 2 months in responders until disease progression, for up to 2 years
chemotherapy
CHOP (6 cycles of 21 days), CVP (8 cycles of 21 days), Bendamustine (6 cycles of 28 days). Patients with follicular lymphoma are receiving either CHOP, CVP or Bendamustine as background chemotherapy as selected by each participating site at study start. Background chemotherapy for patients with non-follicular lymphoma will be chosen by the site individually for each patient.

Primary Outcomes

Measure
Progression-free survival in patients with follicular lymphoma, investigator-assessed according to the Revised Response Criteria for Malignant Lymphoma
time frame: up to approximately 7.5 years

Secondary Outcomes

Measure
Progression-free survival in the overall study population, investigator-assessed
time frame: up to approximately 7.5 years
Progression-free survival, Independent Review Committee - assessed
time frame: up to approximately 7.5 years
Response (overall response and complete response), investigator-assessed
time frame: 168 days
Response (overall response and complete response), Independent Review Committee - assessed
time frame: 168 days
Overall survival
time frame: up to approximately 10.7 years
Event-free survival
time frame: up to approximately 7.5 years
Disease-free survival
time frame: up to approximately 7.5 years
Duration of response
time frame: up to approximately 7.5 years
Time to next anti-lymphoma treatment
time frame: up to approximately 10.7 years
Safety: Incidence of adverse events
time frame: up to approximately 10.7 years
Patient-reported outcomes (Functional Assessment of Cancer Therapy for Lymphoma scale, EuroQol EQ-5D questionnaire)
time frame: up to approximately 7.5 years
Medical resource utilization (hospitalizations, subsequent drug therapies, medical and surgical procedures)
time frame: up to approximately 7.5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult patients, >/= 18 years of age - CD20-positive indolent B-cell non-Hodgkin's lymphoma (follicular lymphoma or splenic, nodal or extranodal marginal zone lymphoma) - Stage III or IV disease, or Stage II bulky disease (defined as tumour diameter >/= 7 cm), requiring treatment - For patients with follicular lymphoma: requirement for treatment according to GELF criteria - For patients with symptomatic marginal zone lymphoma: disease that is de novo or has relapsed following local therapy (i.e. surgery or radiotherapy) and requires therapy as assessed by the investigator - At least one bi-dimensionally measurable lesion (>2 cm in its largest dimension by CT scan or MRI) - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 - Adequate hematologic function Exclusion Criteria: - Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma - Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's macroglobulinaemia - Ann Arbor Stage I disease - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy, known hypersensitivity to any of the study drugs or sensitivity to murine products, or history of sensitivity to mannitol - For patients with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma with chemotherapy, immunotherapy, or radiotherapy - For patients with non-follicular lymphoma: prior treatment with chemotherapy or immunotherapy - Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle 1 - Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results - For patients who will be receiving CHOP: LVEF <50% by MUGA scan or echocardiogram - History of prior malignancy with the exception of curatively treated basal or squamous cell carcinoma of the skin and low-grade in situ carcinoma of the cervix - Known active infection, or major episode of infection within 4 week prior to the start of Cycle 1 - Vaccination with a live vaccine within 28 days prior to randomization - Recent major surgery (within 4 weeks prior to start of Cycle 1), other than for diagnosis - Abnormal laboratory values as defined by protocol for creatinine, creatinine clearance, AST or ALT, total bilirubin, INR, PTT or aPPT, unless these abnormalities are due to underlying lymphoma - Positive as per protocol definition for HIV, HTLV1, hepatitis C or chronic hepatitis B - Pregnant or lactating women - Life expectancy < 12 months - Participation in another clinical trial with drug intervention within 28 days prior to start of Cycle 1 and during study

Additional Information

Official title A Multicentre, Phase III, Open Label, Randomized Study in Previously Untreated Patients With Advanced Indolent Non-Hodgkin's Lymphoma Evaluating the Benefit of GA101 (RO5072759) + Chemotherapy Compared to Rituximab + Chemotherapy Followed by GA101 or Rituximab Maintenance Therapy in Responders.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.
Location data was received from the National Cancer Institute and was last updated in September 2016.