Lenalidomide in Patients With Chronic Lymphocytic Leukemia Older Than 65 Years of Age

Inclusion Criteria: * Patients with either previously untreated or treated disease must have either intermediate or high-risk chronic lymphocytic leukemia as defined by the three-stage Rai system. Patients with Rai intermediate risk disease should meet the criteria for active disease as outlined by the NCI Working Group guidelines (including weight loss, fatigue, fevers, evidence of progressive marrow failure, splenomegaly, progressive lymphadenopathy, or progressive lymphocytosis with a rapid doubling time)(49). * MSKCC pathologist must confirm patient's disease. * To be considered CLL the patient must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells * Immunophenotypic (or immunohistochemical) analysis of the malignant lymphocytes should demonstrate that the cells are B-cells. Typically these cells should also express CD5 and CD23. It is recognized that an occasional patient with CLL may have a slightly aberrant immunophenotype. All such cases need to be reviewed with the principal investigator prior to being registered for the study. Patients with small lymphocytic lymphoma (CLL type) will be eligible for this study. * Age ≥ 65 years of age. * Karnofsky performance status ≥ 50% * ANC ≥ 0.8 and platelet count ≥ 30,000 * Total creatinine ≤ 2.0mg/dl or creatinine clearance ≥ 30ml/min. * Total bilirubin ≤ 3.0 mg/dL (not attributable to autoimmune hemolytic anemia). * Signed informed consent, which indicates the investigational nature of this study, is required. * No patient may be entered onto the study without consultation with the principal investigator or his designee. * Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Exclusion Criteria: * Patients with significant active infections. * Men should use effective contraception. * Patients known positive for HIV or with active infection from hepatitis, A, B, or C. * Concomitant chemotherapy or radiotherapy while on protocol. * Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome. * History of thromboembolic disease within the past 6 months, regardless of anti-coagulation. * Myocardial infarction within 6 months prior to enrollment, or New York Hospital Association (NYHA) Class III or IV heart failure , uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * 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.