Fludarabine, Cyclophosphamide, and Rituximab in Treating Patients Who Have Chronic Lymphocytic Leukemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.
PURPOSE: Phase II trial to study the effectiveness of fludarabine plus high-dose cyclophosphamide and rituximab in treating patients who have previously untreated chronic lymphocytic leukemia.
Drug: fludarabine phosphate
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Fludarabine Induction With Sequential High Dose Cyclophosphamide and Rituximab as Consolidation Therapy for Previously Untreated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia|
- Overall Response Rate [ Time Frame: 3 years ]Response was determined as indicated in the protocol. The categories are: complete response, nodular partial response, partial response and failure. The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. The laboratory and radiographic studies which were abnormal pre-study, will be repeated to document the degree of maximal response.
- Utilize Flow Cytometry and Polymerase Chain Reaction as Sensitive Measures of Minimal Residual Disease [ Time Frame: 3 years ]The flow cytometric response and the molecular polymerase chain reaction (PCR) response was captured as indicated in the protocol. Immunophenotypic analysis of bone marrow and/ or peripheral blood demonstrate a normal k:λ ratio and a normal number of CD5/CD19 (or CD5/CD20) dual staining cells (<5% of the lymphocyte gate).
- Overall Survival Status [ Time Frame: up to 5 years ]The 5 year survival rate. The survival of patients with this disease is dependent on the stage of disease. Two useful staging systems are: Three-stage Rai System Clinical Feature and the Binet System.
|Study Start Date:||September 1998|
|Study Completion Date:||May 2009|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
Experimental: intermediate or high risk chronic lymphocytic leukemia
This is a single-arm open-label pilot study designed to assess the antileukemic activity of a regimen containing sequential administration of fludarabine, high-dose cyclophosphamide, and rituximab.
Filgrastim (300 μg for patients ≤ 70 kg or 480 μg for patients > 70 kg) will be administered beginning two days after each cyclophosphamide dose and given for a total of eight subcutaneous daily doses.Biological: rituximab
Approximately four weeks after the completion of the last cyclophosphamide dose, patients will receive rituximab 375mg/m2 as an intravenous infusion once weekly for four doses.Drug: cyclophosphamide
Cyclophosphamide 3000mg/m2 will be given intravenously q 2 - 3 weeks x 3 doses.Drug: fludarabine phosphate
Fludarabine will be administered intravenously at a dose of 25 mg/m2 per day x 5 days every 4 weeks.
- Determine the response rate in patients with chronic lymphocytic leukemia treated with sequential fludarabine, high dose cyclophosphamide, and rituximab.
- Survival up to 5 years
- Utilize flow cytometry and polymerase chain reaction as sensitive measures of minimal residual disease in these patients.
OUTLINE: This is an open label study.
Patients receive fludarabine IV once daily for 5 days. Treatment is repeated every 4 weeks for 3 or 6 courses.
Three weeks later, cyclophosphamide is administered intravenously every 2-3 weeks for 3 courses. Filgrastim (G-CSF) is administered on days 2-10. Beginning 4 weeks after the last dose of cyclophosphamide, patients receive rituximab by intravenous infusion once weekly for 4 weeks.
Patient are followed every 3 months until death.
PROJECTED ACCRUAL: This study will accrue 30 patients within 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003659
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|Study Chair:||Mark Adam Weiss, MD||Memorial Sloan Kettering Cancer Center|