Fludarabine Combined With Either Alemtuzumab or Rituximab in Treating Patients With Refractory or Relapsed B-Cell Chronic Lymphocytic Leukemia

OBJECTIVES: Primary * Compare the complete response rate in patients with refractory or relapsed B-cell chronic lymphocytic leukemia treated with fludarabine and alemtuzumab vs fludarabine and rituximab. Secondary * Compare the overall response rate in patients treated with these regimens. * Compare 1-year survival of patients treated with these regimens. * Compare time to progression in patients treated with these regimens. * Compare duration of response in patients treated with these regimens. * Compare the adverse event profile of these regimens in these patients. * Compare the molecular response rate in patients treated with these regimens. * Compare lymphocyte and lymphocyte subset recovery (CD3, CD3/CD4, CD3/CD8, CD20) in patients treated with these regimens. * Compare the time to complete response in patients treated with these regimens. * Compare the rate of cytomegalovirus reactivation and time to reactivation in patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to prior treatment with fludarabine (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5. At least 30 minutes before fludarabine administration, patients receive alemtuzumab subcutaneously (SC) on days 1-5. * Arm II: Patients receive fludarabine as in arm I. At least 30 minutes before fludarabine administration, patients receive rituximab IV on days 1 and 4 of course 1 and on day 1 only in subsequent courses. In both arms, treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. An interim assessment is performed during course 4. Patients achieving a partial response or stable disease receive 2 additional courses of therapy (for a total of 6 courses). Patients achieving a complete response (CR) do not receive further treatment beyond CR. Patients are followed weekly for 2 months, monthly for 6 months, every 2 months for 6 months, and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.