Seven years of follow-up & final analysis done in Dec 2012.

This study will assess the

• efficacy (response rate) of oral lenalidomide in the treatment of patients with symptomatic, previously untreated, chronic lymphocytic leukemia (CLL),
• toxicity of lenalidomide in patients with CLL as well as time to progression, stable disease duration and, if responses are observed, response duration.

This is a phase II, nonrandomized, single institution study in symptomatic, previously untreated CLL patients. Subjects will receive the study drug, lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Although a maximal dose of 10 mg daily (days 1-21) will be targeted, if a patient is felt by the investigator to be benefiting from doses less than the target dose (i.e. 2.5 mg or 5 mg daily), the investigator may at his discretion choose to hold the patient at that dose without further escalation. For those patients who have progressive disease after cycle 3, further dose escalations as assessed by response and toxicity at the end of each escalated dose cycle to a maximum of 25 mg (days 1-21) will be allowed. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form.

• Age ≥18 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 ≥ 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.

CTCAE Version 3.0 was used for adverse event grading and categorizing

Original study protocol used a starting lenalidomide dose of 10mg OD for 21days of a 28-day cycle, escalating weekly by 5mg to a target of 25mg daily. Toxicities reported with the first two enrolled patients lead to the current protocol amendment.