Rituximab, Fludarabine, and Cyclophosphamide or Observation Alone in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia

OBJECTIVES:

Primary

• Compare the effect, in terms of event-free survival, of deferred versus immediate treatment with rituximab, fludarabine, and cyclophosphamide in patients with previously untreated Binet stage A chronic lymphocytic leukemia at high risk for disease progression.
• Investigate and define a new prognostic staging system for patients with Binet stage A chronic lymphocytic leukemia.

Secondary

• Compare the time to progression to Binet stages B and C in patients treated with these regimens.
• Compare the overall and progression-free survival of patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Compare the time to treatment in patients treated with these regimens.
• Analyze the pharmacoeconomics of these regimens in these patients.
• Determine the overall response rate (partial and complete) in patients included in the early treatment arm.
• For patients included in the early treatment arm in complete remission, determine the percentage achieving complete molecular remission using the clone-specific CDR-III region as follow-up parameter.
• Determine the duration of response in patients included in the early treatment arm.
• Determine any adverse events related to treatment/safety of treatment.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk factor profile (< 2 risk factors [low risk] vs ≥ 2 risk factors [high risk]). Low-risk patients are assigned to arm II. High-risk patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive rituximab IV on day 1, fludarabine IV on days 1-3, and cyclophosphamide IV on days 1-3. Treatment repeats every 28 days for up to 6 courses.
• Arm II: Patients undergo observation only until disease progression.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Established diagnosis of B-cell chronic lymphocytic leukemia

• First diagnosis within 12 months before inclusion in study
• Previously untreated disease
• Binet stage A disease (Rai stage 0, I, or II)

PATIENT CHARACTERISTICS:

• Life expectancy > 6 months
• ECOG performance status 0-2
• Willingness to accept contraception (if randomized to arm I) for the duration of therapy and 12 months thereafter
• Negative serum pregnancy test
• All parameters for risk stratification (lymphocyte doubling time, cytogenetics, unmutated IgVH, and serum thymidine kinase level > 10) present

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or antibody treatment
• No other concurrent chemotherapy