A Randomized Study Comparing Maintenance Therapy With Subcutaneous Rituximab Continued Until Progression With Observation Only in Patients With Relapsed or Refractory, Indolent Non-Hodgkin's Lymphoma Who Completed and Responded to Rituximab-based Immunochemotherapy Induction and Initial 2-year Rituximab Maintenance Therapy Administered Subcutaneously
Overview
- Phase
- Phase 3
- Intervention
- Chemotherapy (Induction Period)
- Conditions
- Non-Hodgkin's Lymphoma
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 692
- Locations
- 180
- Primary Endpoint
- Maintenance II: Progression-free Survival (PFS) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This multicenter, randomized, open-label, parallel-group study will evaluate the efficacy and safety of subcutaneously administered rituximab in comparison with observation only as maintenance therapy in participants with relapsed or refractory indolent Non-Hodgkin's lymphoma (NHL). All participants will receive induction therapy with rituximab (375 milligrams per square meter [mg/m^2] intravenously [IV] in Cycle 1, then 1400 mg subcutaneous [SC] every 3-4 weeks) plus standard chemotherapy for 6-8 months; followed by 24 months of maintenance I period with rituximab (1400 mg SC every 8 weeks). Participants completing therapy and showing partial or complete response will be randomized to receive either rituximab (1400 mg SC every 8 weeks) or observation with no treatment during maintenance II period and will be followed for at least 15 months. Anticipated time on study treatment is until disease progression, unacceptable toxicity or end of study, whichever occurs first.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed Cluster of Differentiation 20-positive (CD20+) follicular NHL Grade 1, 2 or 3a, or other CD20+ indolent NHL (Waldenström's macroglobulinemia or lymphoplasmacytic lymphoma, marginal zone lymphoma) according to World Health Organization (WHO) classification system
- •Participants must have received and must have relapsed or been refractory to, one or more lines of adequate therapy prior to enrollment, including at least one line consisting of immunotherapy and/or chemotherapy and/or radiotherapy
- •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 2
Exclusion Criteria
- •Transformation to high-grade lymphoma
- •Aggressive lymphoma (for example, mantle cell lymphoma \[MCL\])
- •Presence or history of central nervous system (CNS) lymphomatous disease
- •Other malignancy within 5 years prior to enrollment, except for curatively treated carcinoma in situ of the cervix, squamous cell carcinoma of the skin or basal cell skin cancer, or cervical carcinoma Stage 1B or less, breast cancer in situ or localized prostate cancer Stage T1c if treated with curative intent and relapse- and metastasis-free for at least 2 years prior to enrollment
- •Inadequate hematological, hepatic or renal function
- •Known human immunodeficiency virus (HIV) infection
- •Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B or C)
- •Pregnant or breastfeeding women
Arms & Interventions
Maintenance II Period Observation Only
Participants will receive standard chemotherapy regimen in combination with 375 mg/m\^2 rituximab IV in Cycle 1 (3-4 week-cycles), followed by 1400 mg rituximab SC every 3-4 weeks for 8 cycles (induction period); 1400 mg rituximab SC every 8 weeks for 24 months (Maintenance I period); no treatment in Maintenance II period until disease progression or end of study, whichever occurs first.
Intervention: Chemotherapy (Induction Period)
Maintenance II Period Observation Only
Participants will receive standard chemotherapy regimen in combination with 375 mg/m\^2 rituximab IV in Cycle 1 (3-4 week-cycles), followed by 1400 mg rituximab SC every 3-4 weeks for 8 cycles (induction period); 1400 mg rituximab SC every 8 weeks for 24 months (Maintenance I period); no treatment in Maintenance II period until disease progression or end of study, whichever occurs first.
Intervention: Rituximab
Maintenance II Period Rituximab
Participants will receive standard chemotherapy regimen in combination with 375 mg/m\^2 rituximab IV in Cycle 1 (3-4 week-cycles), followed by 1400 mg rituximab SC every 3-4 weeks for 8 cycles (induction period); 1400 mg rituximab SC every 8 weeks for 24 months (Maintenance I period); 1400 mg rituximab SC every 8 weeks until disease progression or end of study, whichever occurs first (Maintenance II period).
Intervention: Chemotherapy (Induction Period)
Maintenance II Period Rituximab
Participants will receive standard chemotherapy regimen in combination with 375 mg/m\^2 rituximab IV in Cycle 1 (3-4 week-cycles), followed by 1400 mg rituximab SC every 3-4 weeks for 8 cycles (induction period); 1400 mg rituximab SC every 8 weeks for 24 months (Maintenance I period); 1400 mg rituximab SC every 8 weeks until disease progression or end of study, whichever occurs first (Maintenance II period).
Intervention: Rituximab
Outcomes
Primary Outcomes
Maintenance II: Progression-free Survival (PFS) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia
Time Frame: From randomization (Maintenance II) up to disease progression or death, whichever occurs first (up to approximately 24 months)
Progression free survival from randomization (PFSrand) is defined as the time from date of randomization to the date of first documented disease progression or death, whichever occurs first. One participant died in Induction before randomization and one participant died in Maintenance II Observation arm due to an SAE and were not considered in the analysis as no death page was completed. The Observation arm did not include one participant with AE outcome of death reported retrospectively 2 months after discontinuation from study (censored as having no event on Day 456 post-randomization).
Secondary Outcomes
- Number of Participants With Adverse Events (AEs), Serious AEs, and Infusion/Administration-related Reactions (IRRs/ARRs)(From day of first rituximab induction dose up to day of disease progression, or discontinuation of treatment for any reason (up to approximately 87 months))
- Overall Survival(From day of first rituximab induction dose up to death (up to approximately 87 months))
- Time to Next Lymphoma Treatment (TNLT)(From day of first rituximab induction dose up to any new lymphoma treatment (up to approximately 87 months))
- Maintenance I: Percentage of Participants With Conversion of PR to CR Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia(From day of first rituximab induction dose up to end of Maintenance I period (up to approximately 32 months))
- Progression-free Survival (PFS) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia(From day of first rituximab induction dose up to disease progression or death, whichever occurs first (up to approximately 87 months))
- Maintenance II: Overall Survival(From randomization (Maintenance II) up to death (up to approximately 24 months))
- Event-free Survival (Time to Treatment Failure) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia(From day of first rituximab induction dose up to day of any treatment failure, including disease progression, or discontinuation of treatment for any reason (up to approximately 87 months))
- Percentage of Participants With Partial or Complete Tumor Response (PR/CR) Assessment at End of Induction Using 1999 International Working Group Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia(From day of first rituximab induction dose up to end of induction period (up to approximately 8 months))