Randomized Phase-III Trial Comparing Fludarabine and Cyclophosphamide Plus Rituximab (FCR) to FC and MabCampath (FCCam) for Previously Untreated Fit Patients With Chronic Lymphocytic Leukemia (CLL)
Overview
- Phase
- Phase 3
- Intervention
- rituximab
- Conditions
- Leukemia
- Sponsor
- French Innovative Leukemia Organisation
- Enrollment
- 178
- Locations
- 1
- Primary Endpoint
- Progression-free survival at 36 months
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to kill cancer cells or stop them from growing. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. It is not yet known whether giving fludarabine and cyclophosphamide together with rituximab is more effective than giving fludarabine and cyclophosphamide together with alemtuzumab in treating B-cell chronic lymphocytic leukemia.
PURPOSE: This randomized phase III trial is studying giving fludarabine together with cyclophosphamide and rituximab to see how well it works as first-line therapy compared with giving fludarabine together with cyclophosphamide and alemtuzumab in treating patients with B-cell chronic lymphocytic leukemia.
Detailed Description
OBJECTIVES: Primary * To compare 36-month progression-free survival in patients with Binet stage B or C B-cell chronic lymphocytic leukemia treated with first-line therapy comprising fludarabine phosphate and cyclophosphamide and either rituximab or alemtuzumab. Secondary * To compare the disease-free survival, event-free survival, and overall survival of patients treated with these regimens. * To compare time to next treatment in patients treated with these regimens. * To compare the overall response rate (complete response \[CR\] and partial response \[PR\]) in patients treated with these regimens. * To compare the rate of phenotypic and molecular response in patients treated with these regimens. * To compare the duration of phenotypic, molecular, complete and partial responses in patients treated with these regimens. * To compare the response rates and survival times in biological subgroups. * To compare the rates of treatment-related adverse effects in patients treated with these regimens. * To compare the quality of life of patients treated with these regimens. * Minimal residual disease study. OUTLINE: This is a multicenter study. Patients are stratified according to Ig mutational status and cytogenetic abnormalities. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive rituximab IV on day 1 and fludarabine phosphate and cyclophosphamide IV or orally on days 2-4 of course 1. Beginning in course 2 and for all subsequent courses, patients receive rituximab IV on day 1 and fludarabine phosphate and cyclophosphamide IV or orally on days 1-3. * Arm II: Patients receive alemtuzumab subcutaneously, oral fludarabine phosphate, and oral cyclophosphamide on days 1-3. In both arms, treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
FCCAM
Fludarabine-Cyclophosphamide-Campath (FCCam) Oral Fludarabine: 40 mg/m2 per os, D1 to D3 Oral Cyclophosphamide: 250 mg/m2/day as one dose at noon, D1 to D3 Campath®: 30 mg sc, D1 to D3 without dose escalation
Intervention: rituximab
FCCAM
Fludarabine-Cyclophosphamide-Campath (FCCam) Oral Fludarabine: 40 mg/m2 per os, D1 to D3 Oral Cyclophosphamide: 250 mg/m2/day as one dose at noon, D1 to D3 Campath®: 30 mg sc, D1 to D3 without dose escalation
Intervention: cyclophosphamide
FCCAM
Fludarabine-Cyclophosphamide-Campath (FCCam) Oral Fludarabine: 40 mg/m2 per os, D1 to D3 Oral Cyclophosphamide: 250 mg/m2/day as one dose at noon, D1 to D3 Campath®: 30 mg sc, D1 to D3 without dose escalation
Intervention: fludarabine
FCR
Fludarabine-Cyclophosphamide-Rituximab (FCR) First course: Rituximab 375 mg/m2 on D1. D2 to D4: oral Fludarabine: 40 mg/m2/day as a single morning dose oral Cyclophosphamide: 250 mg/m2/day as a single dose at noon Subsequent courses (2 to 6) Rituximab 500 mg/m2 on D1 D1 to D3: oral Fludarabine: 40 mg/m2/day as a single morning dose oral Cyclophosphamide: 250 mg/m2/day as a single dose at noon
Intervention: Campath
FCR
Fludarabine-Cyclophosphamide-Rituximab (FCR) First course: Rituximab 375 mg/m2 on D1. D2 to D4: oral Fludarabine: 40 mg/m2/day as a single morning dose oral Cyclophosphamide: 250 mg/m2/day as a single dose at noon Subsequent courses (2 to 6) Rituximab 500 mg/m2 on D1 D1 to D3: oral Fludarabine: 40 mg/m2/day as a single morning dose oral Cyclophosphamide: 250 mg/m2/day as a single dose at noon
Intervention: cyclophosphamide
Outcomes
Primary Outcomes
Progression-free survival at 36 months
Time Frame: 36 months follow up
Secondary Outcomes
- Disease-free survival(36 months follow up)
- Event-free survival(36 months follow up)
- Overall survival(36 months follow up)
- Time to next treatment(36 months follow up)
- Overall response rate (complete response [CR] and partial response [PR])(36 months follow up)
- Duration of phenotypic, molecular, NCI complete and partial responses(36 months follow up)
- Response rates and survival times in biological subgroups(36 months follow up)
- Treatment-related adverse effects(36 months follow up)