Inclusion Criteria:

• Understand and voluntarily sign an informed consent form.
• Age ³18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• A confirmed diagnosis of B-cell CLL by NCI Working Group criteria
• No prior systemic therapy for CLL. Steroid therapy alone for autoimmune cytopenias (anemia or thrombocytopenia) is NOT considered a prior systemic therapy.
• Radiation: Patients may have received prior radiation therapy restricted to < 25% of functioning bone marrow. Patients must be > 4 weeks since last treatment with radiation therapy.
• Surgery: previous surgery is permissible. Patient must be > 4 weeks since any major surgery.

• Patients must have symptomatic disease requiring therapy. One or more of the following must be present to be eligible:

  • Symptomatic lymphadenopathy
  • Hepatomegaly and/or splenomegaly
  • Anemia (Hb <110 g/L)
  • Thrombocytopenia (platelets <100)
  • Fatigue, weight loss, night sweats, fever (without infection) or other constitutional symptoms felt to require treatment as per treating physician discretion
  • Persistent rise in lymphocyte count with doubling time of < 12 months
• ECOG performance status of </= 2 at study entry .
• Laboratory Requirements: (must be done within 7 days prior to first study drug dose)

Hematology: Absolute granulocytes (AGC) > 1.0 x 109/L Platelets > 50 x 109/L Chemistry: Serum creatinine < 1.5 x UNL Bilirubin < 1.5 x UNL AST (or ALT if AST < 2.5 x UNL not available)

• Women of childbearing potential (WCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to therapy and repeated within 24 hours of starting study drug and must either commit to continued abstinence from heterosexual sexual intercourse or begin TWO acceptable methods of birth control, one highly effective methods and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. In addition, sexually active WCBP must agree to ongoing pregnancy testing.. Men must agree not to father a child and agrees to use a condom if his partner is of child bearing potential.
• Disease free of prior malignancies for ³ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast

Exclusion Criteria:

• Patients who fulfill any of the following criteria are not eligible for admission to the study:
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or lactating females. (Lactating females must agree not to breast feed while taking lenalidomide).
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Patients previously or currently receiving treatment with other anti-cancer therapy for CLL
• Lymphoproliferative disease other than CLL (includes patients with prolymphocytic leukemia, mantle cell lymphoma, and those who have transformed to a more aggressive lymphoma, or Richter's syndrome).
• Known hypersensitivity to thalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Any prior use of lenalidomide.
• Concurrent use of other anti-cancer agents or treatments.
• Known positive for HIV or infectious hepatitis, type A, B or C.