RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as pentostatin and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and lenalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with pentostatin, cyclophosphamide, and lenalidomide works in treating patients with previously untreated B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

OBJECTIVES:

Primary

• To assess the rate of complete and overall response using pentostatin, cyclophosphamide, and rituximab (PCR) followed by consolidation with lenalidomide in patients with previously untreated B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma.

Secondary

• To assess the proportion of patients who convert from a nodular partial response (nPR), PR, or stable disease after completing PCR to a complete response (CR) after 6 cycles of consolidation with lenalidomide.
• To assess the proportion of patients who convert from a CR with detectable minimal residual disease (MRD) after PCR to a CR with MRD negative state after 6 courses of consolidation with lenalidomide.
• To assess the proportion of patients who convert from a CR with detectable MRD, nPR, PR, or stable disease with residual disease after PCR to a CR with MRD negative state after 6 cycles of consolidation with lenalidomide.
• To monitor and assess toxicity of this regimen.
• To determine if molecular prognostic parameters (e.g., ZAP-70, CD38, cytogenetic abnormalities identified by FISH, IgVH mutation status) relate to response to PCR-lenalidomide therapy.
• To use evaluation of MRD to determine the duration of lenalidomide therapy.
• To determine the progression-free survival in CLL patients using this treatment regimen.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive rituximab IV over 4 hours on days 1 and 2 of course 1, and over 1 hour on day 1 of each subsequent course. Patients also receive pentostatin IV over 30 minutes and cyclophosphamide IV over 30 minutes on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Consolidation therapy: Beginning 2 months after completion of induction therapy, patients receive oral lenalidomide once daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
• Continuation therapy: Patients with residual disease continue to receive lenalidomide as in consolidation therapy until they achieve a minimal residual disease-negative status or complete remission. Patients who achieve complete response with no detectable disease discontinue therapy and enter the observation phase.

Blood samples are collected periodically during treatment for translational and pharmacologic studies. Samples are analyzed for immunoglobulin heavy chain gene mutational status, ZAP-70 status, and levels of VEGF, bFGF, thrombospondin, and TGF-beta by ELISA; and for the effects of therapy on immune function. Samples are also stored for future research. Bone marrow aspirate samples are analyzed for minimal residual disease by flow cytometry.

After completion of study treatment, patients are followed every 90 days for 3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), meeting the following criteria:

  • Biopsy-proven SLL according to WHO criteria

  • CLL diagnosis* according to NCI working group criteria as evidenced by all of the following:

    • Peripheral blood lymphocyte count of > 5,000/mm³

    • Small to moderate peripheral blood lymphocyte with < 55% prolymphocytes

    • Immunophenotyping consistent with CLL defined as:

      • B-cell markers with CD5 antigen in the absence of other pan-T-cell markers (e.g., CD3, CD2)
      • CD19, CD20, or CD23
      • Dim surface immunoglobulin expression
      • Exclusively kappa or lambda light chains

    • Diagnosis of mantle cell lymphoma must be excluded by negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy NOTE: *Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL

• Previously untreated disease and meets ≥ 1 of the following criteria*:

  • At least 1 or more of the following disease-related symptoms:

    • Weight loss > 10% within the previous 6 months
    • Extreme fatigue attributed to CLL
    • Fevers > 100.5º F for 2 weeks without evidence of infection
    • Night sweats without evidence of infection

  • Evidence of progressive marrow failure as manifested by the development of or worsening anemia (i.e., hemoglobin ≤ 11 g/dL) and/or thrombocytopenia (i.e., platelet count ≤ 100,000/mm³) not due to autoimmune disease

  • Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly

  • Progressive lymphocytosis due to CLL with an increase of > 50% over a 2-month period or an anticipated doubling time < 6 months NOTE: *Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3

• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

• Total bilirubin ≤ 3.0 times ULN (unless due to Gilbert disease)

  • Direct bilirubin < 1.5 mg/dL for Gilbert disease to be diagnosed if total bilirubin > 3.0 times ULN

• AST and ALT ≤ 3.0 times ULN (unless due to hemolysis or CLL)

• Willing to provide blood samples

• Able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use low molecular weight heparin)

• Not pregnant or nursing

• Negative pregnancy test

• Female patients must use effective double-method contraception beginning 1 month prior to, during, and for 4 weeks after completion of study treatment

• Male patients must use effective contraception during and for 4 weeks after completion of study treatment

• No comorbid conditions, including any of the following:

  • New York Heart Association class III or IV heart disease
  • Recent myocardial infarction (< 1 month)
  • Uncontrolled infection
  • Infection with HIV/AIDS

• No other active primary malignancy requiring treatment or that limits survival to ≤ 2 years

• No history of deep venous thrombosis or pulmonary embolism ≤ 12 months prior to study registration

• No active hemolytic anemia requiring immunosuppressive or other pharmacologic therapy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemotherapy or monoclonal antibody-based therapy for treatment of CLL

• Nutraceutical treatments with no established benefit in CLL (e.g., epigallocatechin gallate or other herbal treatments) are not considered prior therapy

• More than 4 weeks since prior radiotherapy

• At least 4 weeks since prior major surgery

• No concurrent corticosteroids

  • Concurrent low doses of steroids (e.g., < 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical conditions allowed
  • Prior use of corticosteroids allowed

• No prior thalidomide or lenalidomide

• No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g., warfarin)

  • Doses of ≤ 2 mg daily allowed for thrombosis prophylaxis
  • Prophylactic doses of low molecular weight heparin allowed