Cladribine and Rituximab as Remission Induction Therapy Followed By Rituximab and Stem Cell Mobilization in Treating Patients With CLL

OBJECTIVES:

Primary

• Determine the efficacy and tolerability of cladribine and rituximab as remission induction therapy in patients with chronic lymphocytic leukemia.
• Determine the complete remission rate in patients treated with this regimen.

Secondary

• Determine the very good partial remission rate and nodular partial remission rate in patients treated with this regimen.
• Determine the toxicity of this regimen, in terms of hemotoxicity and infection rate, in these patients.
• Determine the efficacy of in vivo purging with rituximab measured by immunophenotyping in these patients.
• Determine the feasibility of stem cell harvest in these patients after treatment with this induction therapy regimen and in vivo purging with rituximab.

OUTLINE: This is a multicenter study.

• Remission induction: Patients receive cladribine subcutaneously (SC) on days 1-5. During courses 2-4, patients also receive rituximab IV on day 1. Treatment repeats every 28 days for up to 4 courses in the absence of unacceptable toxicity. If unacceptable toxicity persists, patients receive rituximab alone.

Patients not achieving a complete remission (CR), very good partial remission (VGPR), or nodular partial remission (NPR) receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for up to 4 courses or until patients achieve a CR, VGPR, or NPR.

Patients achieving a CR, VGPR, or NPR proceed to stem cell mobilization and in vivo purging.

• Stem cell mobilization and in vivo purging: Beginning 8-10 weeks after the first day of the last course of remission induction or CHOP, patients receive rituximab IV on days 1 and 8, cyclophosphamide IV over 4 hours on day 2, and filgrastim (G-CSF) SC daily beginning on day 4 and continuing until the last day of apheresis. Patients undergo apheresis on days 11-14.

PROJECTED ACCRUAL: A total of 17-41 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL)

• CD5 positive and CD23 positive
• Binet stage B, C, or progressive A
• Newly diagnosed disease OR no more than 1 prior alkylating agent regimen (e.g., chlorambucil or cyclophosphamide with or without prednisone)

PATIENT CHARACTERISTICS:

Age

• 18 to 65

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• No autoimmune hemolytic anemia
• No immune thrombocytopenia

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN*
• AST and ALT no greater than 2.5 times ULN* NOTE: *Unless clearly related to CLL liver involvement

Renal

• Creatinine clearance greater than 50 mL/min

Cardiovascular

• Ejection fraction at least 50%
• No severe heart failure
• No unstable angina pectoris
• No significant arrhythmia requiring chronic treatment
• No myocardial infarction within the past 3 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after study participation
• HIV negative
• No active infection
• No positive Coombs' test
• No history of significant neurologic or psychiatric disorders, including psychotic disorders or dementia
• No seizure disorder
• No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix
• No prior allergic reaction or hypersensitivity to study drugs or attributed to compounds of similar chemical or biological composition to study drugs or other study agents
• No uncontrolled diabetes mellitus
• No gastric ulcers
• No active autoimmune disease
• No alcohol or drug abuse
• No other concurrent serious underlying medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior purine analogs (e.g., cladribine or fludarabine)

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• More than 30 days since prior clinical trial participation
• No other concurrent experimental drugs