A Randomized, Open Label Study to Assess the Effect of Maintenance Treatment With Mabthera (Rituximab) Versus No Treatment, After Induction Treatment With Rituximab, Cladribine and Cyclophosphamide (RCC) on Progression-Free Survival in Previously Untreated Patients With Progressive B-Cell Chronic Lymphocytic Leukemia
Overview
- Phase
- Phase 3
- Intervention
- Cladribine
- Conditions
- Lymphocytic Leukemia, Chronic
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 128
- Locations
- 6
- Primary Endpoint
- Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This study will assess the effect of maintenance treatment with rituximab in comparison with observation period (no treatment), in participants with progressive B-cell CLL who have had previous first-line induction treatment with rituximab, cladribine and cyclophosphamide (RCC regimen). After 6 months of RCC induction therapy, participants will be randomized either to receive maintenance treatment with rituximab or to receive no treatment (observation only) for 96 weeks. Participants completing maintenance/observation period will be followed-up for approximately 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Immunologically confirmed diagnosis of B-cell CLL
- •Rai stage I-IV disease with evidence of progression
- •No previous chemotherapy, radiotherapy, or immunotherapy for B-cell CLL
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Exclusion Criteria
- •Active secondary malignancy or transformation to aggressive lymphoma
- •Medical condition requiring chronic use of oral corticosteroids at a dose of 1 mg/kg or 60 mg/m\^2 over 2 weeks
- •Prior treatment with interferon, rituximab or another monoclonal antibody, immunosuppressive treatment or radiotherapy before inclusion to the study
- •History of other malignancies within 2 years before study entry, except for dequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent
Arms & Interventions
Induction: Rituximab, Cladribine, Cyclophosphamide
Participants will receive rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 will be administered in Cycles 2-6. Each cycle will be of 28 days in duration.
Intervention: Cladribine
Induction: Rituximab, Cladribine, Cyclophosphamide
Participants will receive rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 will be administered in Cycles 2-6. Each cycle will be of 28 days in duration.
Intervention: Cyclophosphamide
Induction: Rituximab, Cladribine, Cyclophosphamide
Participants will receive rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 will be administered in Cycles 2-6. Each cycle will be of 28 days in duration.
Intervention: Rituximab
Maintenance Arm: Rituximab
Participants with PR or CR after induction phase who will be randomized to maintenance arm will receive rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants will receive rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).
Intervention: Rituximab
Outcomes
Primary Outcomes
Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL
Time Frame: From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)
PFS was defined as the time from date of randomization to date of PD, relapse, or death due to any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (\>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of \>/=50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000/mcL; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.
Percentage of Participants With Disease Progression (PD), Relapse, or Death Due to Any Cause Assessed According to the National Cancer Institute (NCI) Revised Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL)
Time Frame: From randomization to PD, Relapse, or death due to any cause (overall approximately 5 years)
PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (greater than \[\>\]1.5 centimeters \[cm\]), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of greater than or equal to (\>/=) 50 percent (%) in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000 per microliter (/mcL); transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.
Secondary Outcomes
- Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR(8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129))
- Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29(8 weeks after the last dose of rituximab during induction treatment (Week 29))
- Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL(8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129))
- Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129(12 weeks after the end of maintenance treatment or observation phase (Week 129))
- Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129(12 weeks after the end of maintenance treatment or observation phase (Week 129))
- PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors(From randomization to PD, relapse, or death due to any cause (overall approximately 5 years))
- Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29(8 weeks after the last dose of rituximab during induction treatment (Week 29))