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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining pentostatin and cyclophosphamide with rituximab in treating patients who have chronic lymphocytic leukemia or lymphocytic lymphoma.

Detailed Description
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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.

Official Title
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Pentostatin, Cyclophosphamide And Rituximab (PCR) For B-Cell Chronic Lymphocytic Leukemia (CLL) And Small B-Cell Lymphocytic Lymphoma (SLL): Four Phase II Trials With Patient Stratification Based On Prior Therapy

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: cyclophosphamide
* Drug: pentostatin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: rituximab|nan|
|Drug: cyclophosphamide|nan|
|Drug: pentostatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, recurrent small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma