Overview

This trial is active, not recruiting.

Condition non-hodgkin's lymphoma
Treatments chemotherapy (induction period), rituximab
Phase phase 3
Target CD20
Sponsor Hoffmann-La Roche
Start date December 2011
End date August 2018
Trial size 694 participants
Trial identifier NCT01461928, 2010-023407-95, MO25455

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.

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
(Other)
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.
chemotherapy (induction period)
Participants will receive standard combination chemotherapy every 3-4 weeks for 6 to 8 months. The chemotherapy regimen will be selected at Investigator's discretion, for individual participant. Study protocol does not enforce any particular chemotherapy regimen.
rituximab Rituxan
Participants will receive rituximab according to the regimen specified in individual arm.
(Experimental)
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).
chemotherapy (induction period)
Participants will receive standard combination chemotherapy every 3-4 weeks for 6 to 8 months. The chemotherapy regimen will be selected at Investigator's discretion, for individual participant. Study protocol does not enforce any particular chemotherapy regimen.
rituximab Rituxan
Participants will receive rituximab according to the regimen specified in individual arm.

Primary Outcomes

Measure
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)

Secondary Outcomes

Measure
Percentage of Participants with Adverse Events (AEs), Serious AEs, and Infusion/Injection-related Reactions (IRRs)
time frame: 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)
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
time frame: 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)
Time to Next Lymphoma Treatment (TNLT)
time frame: From day of first rituximab induction dose up to any new lymphoma treatment (up to approximately 87 months)
Overall Survival
time frame: From day of first rituximab induction dose up to death (up to approximately 87 months)
Maintenance II: Overall Survival
time frame: From randomization (Maintenance II) up to death (up to approximately 24 months)
Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia
time frame: From day of first rituximab induction dose up to end of induction period (up to approximately 8 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
time frame: 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
time frame: From day of first rituximab induction dose up to disease progression or death, whichever occurs first (up to approximately 87 months)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title 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
Trial information was received from ClinicalTrials.gov and was last updated in January 2017.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.