Lenalidomide in Treating Patients With High-Risk Chronic Lymphocytic Leukemia

Inclusion Criteria: * Definitive diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria * Must have high-risk B-CLL as defined by ≥ one of the following: * High-risk cytogenetics (either 17p deletion and/or 11q deletion) * Unmutated immunoglobulin heavy chain gene rearrangement * Zap-70 and CD38 expression on leukemic cells will not be used as eligibility criteria for enrollment into the clinical trial * No prior treatment for the management of B-CLL * Patients must have B-CLL requiring therapy as defined by the IWCLL criteria * Must have measurable disease meeting one of the following criteria: * Absolute lymphocyte count \> 5,000/μL * Measurable lymphadenopathy or organomegaly * No tumor lysis syndrome (TLS) by Cairo-Bishop definition * Patients with correction of electrolyte abnormalities allowed * ECOG performance status 0-2 * ANC ≥ 1,500/mm³ * Platelet count ≥ 75,000/mm³ * Creatinine clearance ≥ 30 mL/min * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 3 times ULN (≤ 5 times ULN if hepatic metastases are present) * Uric acid normal * Patients with elevated uric acid allowed provided it is corrected with appropriate pharmacologic measures * Not pregnant or nursing * Negative pregnancy test * Fertile patients must commit to continued abstinence from heterosexual intercourse or use 2 acceptable methods of contraception (1 highly effective method and 1 additional effective method) ≥ 28 days prior to, during, and for ≥ 28 days after discontinuing lenalidomide * Able to adhere to the study visit schedule and other protocol requirements * No serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form * No condition, including the presence of laboratory abnormalities, that would place the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study * No known hypersensitivity to thalidomide or lenalidomide * No history of erythema nodosum characterized by a desquamating rash while taking thalidomide or similar drugs * No history of any other cancer except non-melanoma skin cancer or carcinoma in-situ of the cervix or cancer for which the patient is in complete remission and off therapy for \> 3 years * No cardiac arrest within the past 6 months * No known history of hepatitis B infection, positive hepatitis B surface antigen, or positive hepatitis C antibody * No other concurrent anti-cancer agents or treatments * More than 28 days since any prior experimental drug or therapy * Aspirin (81 or 325 mg) or warfarin sodium daily as prophylactic anticoagulation required * No prior lenalidomide