Fludarabine and Rituximab With or Without Lenalidomide or Cyclophosphamide in Treating Patients With Symptomatic Chronic Lymphocytic Leukemia

Inclusion Criteria:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria:

  • Absolute lymphocytosis > 5,000/μL

    • Lymphocytes must appear mature with < 55% prolymphocytes

  • Bone marrow aspirate smear must show > 30% of all nucleated cells as being lymphoid OR bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL

    • Overall cellularity must be normocellular or hypercellular

  • Lymphocyte phenotype must reveal predominant B-cell monoclonal population sharing a B-cell marker (i.e., CD19, CD20, or CD23) with the CD5 antigen, in the absence of other pan-T-cell markers

    • B-cells must be monoclonal with regard to expression of either kappa or lambda light chains and have surface immunoglobulin expression of low density

      • Patients with bright surface immunoglobulin levels must have CD23 co-expression

• Must have symptomatic, active disease and meet 1 of the following risk criteria according to the modified three-stage Rai staging system:

  • Intermediate-risk disease (i.e., Rai stage I or II) with evidence of active disease as demonstrated by at least one of the following criteria:

    • Massive or progressive splenomegaly, hepatomegaly, and/or lymphadenopathy
    • Presence of weight loss > 10% within the past 6 months
    • Grade 2 or 3 fatigue
    • Fevers > 100.5° F or night sweats for > 2 weeks without evidence of infection
    • Progressive lymphocytosis with an increase of > 50% over a 2-monthperiod or an anticipated doubling time of < 6 months
  • High-risk disease (i.e., Rai stage III or IV)
• Concurrent participation on CALGB-20702 (Leukemia Correlative Studies) required
• Performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use two effective methods of contraception for ≥ 4 weeks prior to, during, and for ≥ 4 weeks after completion of lenalidomide therapy (for patients randomized to arm II or IV)
• Creatinine ≤ 1.5 times upper limit of normal
• No medical condition requiring chronic use of oral corticosteroids

• Patients with HIV infection may be eligible provided they meet the following criteria:

  • CD4-positive cell count > 350/mm³
  • HIV viral load< 10,000 copies HIV RNA/mL (if not on anti-HIV therapy) OR < 50 copies HIV RNA/mL (if on anti-HIV therapy)
  • No evidence of hepatitis B or C infection
  • No evidence of resistant strains of HIV
  • No history of AIDS-defining condition
• No prior therapy for CLL, including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
• No concurrent zidovudine or stavudine
• No concurrent hormones or other chemotherapy, except steroids for hypersensitivity reactions or new adrenal failure or hormones for non-disease-related conditions (e.g., insulin for diabetes)
• No concurrent chronic oral steroids
• No concurrent palliative radiotherapy
• No concurrent epoetin alfa or darbepoetin alfa during remission consolidation therapy (for patients randomized to arm II or IV)
• Concurrent participation on CALGB-9665 allowed