Combination Chemotherapy and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

OBJECTIVES:

• Determine the efficacy of pentostatin, cyclophosphamide, and rituximab, in terms of response rate, time to treatment failure, time to disease progression, durability of response, and overall survival, in patients with B-cell chronic lymphocytic leukemia or small B-cell lymphocytic lymphoma.
• Determine the safety of this regimen, in terms of acute, subacute, and chronic toxicity, in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (no prior chemotherapy for chronic lymphocytic leukemia vs prior purine analog-based therapy [fludarabine or cladribine] but no alkylator therapy vs prior alkylator-based therapy [chlorambucil or cyclophosphamide] but no prior purine analog therapy vs prior therapy with alkylators and purine analogs, but not as combination therapy).

• First course: Patients receive rituximab IV over 1-4 hours on days 1-3 and pentostatin IV over 10-30 minutes and cyclophosphamide IV over 30-60 minutes on day 1.
• All subsequent courses: Patients receive rituximab IV over 60 minutes, pentostatin IV over 10-30 minutes, and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 160-240 patients (40-60 per stratum) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small B-cell lymphocytic lymphoma (SLL) with the following:

• Lymph node biopsy interpreted as SLL or consistent with CLL or all of the following:

• Peripheral lymphocyte count greater than 5,000/mm^3 with small to moderate peripheral lymphocytes and no more than 55% prolymphocytes
• Bone marrow aspirate containing at least 30% lymphoid cells
• Immunophenotypic evaluation of peripheral blood lymphocytes demonstrating monoclonality of B lymphocytes with all of the following:

• CD19 or CD20 coexpressed with CD5 antigen in the absence of other pan-T- cell markers (e.g., CD2 or CD3)
• Expression of CD23 on CLL cells or Dim B-cell expression of kappa or lambda light chains
• Measurable disease with any of the following:

• 1 or more lymph nodes at least 1.5 cm by CT scan
• Splenomegaly by CT scan
• Peripheral lymphocyte count greater than 5,000/mm3 with coexpression of CD5 and B-cell markers
• Bone marrow aspirate with at least 30% lymphoid cells
• No mantle cell lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 2 years

Hematopoietic

• See Disease Characteristics
• No immune thrombocytopenia
• No hemolytic anemia

Hepatic

• Bilirubin no greater than 3 times upper limit of normal (ULN)
• SGOT no greater than 3 times ULN (unless due to hemolysis or CLL)
• No hepatitis

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No cardiac dysfunction
• No New York Heart Association class III or IV heart disease
• No myocardial infarction within the past month

Other

• HIV negative
• No active acute or chronic infection
• No immunosuppressive diseases
• No autoimmune disorder
• No secondary malignancy that is projected to limit life expectancy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Chemotherapy
• No prior rituximab
• At least 4 weeks since prior biologic therapy

Chemotherapy

• At least 4 weeks since prior chemotherapy
• No prior combination chemotherapy and rituximab or other antibody therapy
• No prior combination chemotherapy comprising an alkylating agent and a purine nucleoside analog (i.e., cyclophosphamide or chlorambucil in combination with fludarabine, cladribine, or pentostatin)
• No prior pentostatin

Endocrine therapy

• At least 4 weeks since prior corticosteroids
• No concurrent supra-physiologic doses of corticosteroids

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• At least 4 weeks since prior major surgery

Other

• No concurrent immunosuppressive therapy (e.g., cyclosporine)