Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL)
Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL)
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.