Clinical Trials

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