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.

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL), defined as:

• Peripheral lymphocyte count > 5,000/mm^3
• Clonal CD5-, CD19-, and CD23-positive lymphocytes
• Refractory to OR relapsed after prior first-line therapy
• No CNS involvement with CLL

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal

• Creatinine ≤ 1.5 times ULN

Immunologic

• No active cytomegalovirus
• No prior fludarabine-associated autoimmune hemolytic anemia or immune thrombocytopenic purpura
• No active infection requiring treatment with antibiotic, antiviral, or antifungal agents
• No prior significant allergic reaction to antibody therapies that required therapy to be discontinued
• HIV negative

Other

• No active secondary malignancy
• No other concurrent severe diseases or mental disorders
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior alemtuzumab and/or rituximab
• No prior bone marrow transplantation
• No concurrent thrombopoietin or pegfilgrastim

Chemotherapy

• More than 3 weeks since prior fludarabine

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 3 months since prior investigational drugs
• No other concurrent cytotoxic therapy