Combination Chemotherapy With or Without Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

OBJECTIVES:

Primary

• Assess the efficacy and safety of fludarabine, cyclophosphamide, and mitoxantrone hydrochloride with or without rituximab in patients with previously treated chronic lymphocytic leukemia.
• Determine the overall response rate, defined as complete or partial remission, in these patients.

Secondary

• Determine the proportion of patients with undetectable minimal residual disease.
• Determine the 2-year progression-free survival of these patients.
• Determine the 2-year overall survival of these patients.
• Determine the toxicity of this regimen.

OUTLINE: This is a randomized, controlled, open-label, parallel group, multicenter study. Patients are stratified according to prior treatment with fludarabine (refractory vs not refractory or naive). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral fludarabine* and oral cyclophosphamide* on days 1-5 and mitoxantrone hydrochloride IV on day 1.
• Arm II: Patients receive fludarabine*, cyclophosphamide*, and mitoxantrone hydrochloride as in arm I. Patients also receive rituximab IV on day 1.

NOTE: *If the oral regimen is not tolerated, patients may receive fludarabine IV and cyclophosphamide IV on days 1-3.

Treatment in both arms repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia requiring therapy
• Previously treated with ≥ 1 chemotherapeutic regimen

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy ≥ 12 weeks
• Creatinine clearance ≥ 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile female patients must use effective contraception for 4 weeks before, during, and for 6 months after completion of study treatment
• Fertile male patients must use effective contraception during and for 6 months after completion of study treatment
• No history of anaphylaxis after exposure to rat or mouse-derived complementary-determining region (CDR)-grafted humanized monoclonal antibodies
• No toxicity attributable to purine analogues (e.g., autoimmune hemolytic anemia, neurological toxicity, or allergy)
• No active infection
• No other severe (particularly cardiac or pulmonary) diseases or mental disorders that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior fludarabine (or other purine analogues) combined with cyclophosphamide and mitoxantrone hydrochloride
• No prior rituximab, either alone or in combination with chemotherapy