OBJECTIVES: Primary * Determine the objective response rate (complete remission, partial remission \[PR\], or nodular PR) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab (PCR) followed by CAMPATH-1H . * Determine the presence of minimal residual disease in patients treated with this regimen who achieve a CR or nPR Secondary * Determine the toxicity of this regimen in these patients. * Determine the overall and progression-free survival of patients treated with this regimen. * Evaluate the number of patients who after PCR (or during PCR for PD), only achieve a PR, SD, or PD and who subsequently convert to a higher response category after CAMPATH-1H . Exploratory * Assess the angiogenic profile (i.e., secretion levels of pro- versus anti-angiogenic molecules) of CLL B cell clones as well as bone marrow angiogenesis (i.e., vascular density by immunohistochemistry) at baseline, after PCR, after CAMPATH-1H, every six months (serum only), and at time of response assessment (marrow). * Determine the V_H gene mutation status and CD38 expression of the B-CLL clones at study entry and at the end of the therapy and assess the association between the VH gene mutation status and CD38 expression and clinical outcome. * Determine surface phenotype (by flow cytometry) and genetic defects (by CLL FISH panel) information on CLL-B cell clones and associate with clinical outcome. * Monitor the T-cell status by repertoire and flow cytometry analysis to determine the nature and extent of T-cell deficiency induced by the PCR and CAMPATH-1H treatment and assess any association with clinical outcome and toxicities.
Inclusion criteria: * Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria: * Peripheral blood absolute lymphocyte count greater than 5,000/mm\^3 * Lymphocytosis must comprise small to moderate size lymphocytes with no greater than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically * Phenotypically characterized CLL defined by the following: * Predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-cell markers (CD3 or CD2) * B cell expresses either kappa or lambda light chains * Surface immunoglobulin with low cell surface density expression * Requires chemotherapy, as indicated by any of the following: * Disease-related symptoms * Weight loss of 10% or more within the past 6 months * Extreme fatigue * Fevers greater than 100.5°F for 2 weeks without evidence of infection * Night sweats without evidence of infection * Evidence of progressive marrow failure manifested by the development of or worsening anemia (hemoglobin no greater than 10 g/dL) and/or thrombocytopenia (platelet count no greater than 100,000/mm\^3) * Massive (i.e., greater than 6 cm below left costal margin) or progressive splenomegaly * Massive nodes or clusters (i.e., greater than 10 cm in longest diameter) or progressive adenopathy * Progressive lymphocytosis with an increase of greater than 50% over a 2-month period OR an anticipated doubling time of less than 6 months * Demonstrated progression after at least 1 course of either an alkylating agent-based or purine nucleoside-based (e.g., fludarabine) regimen OR failed to achieve a meaningful response OR relapsed after prior therapy * Patients who have relapsed after a pentostatin-based regimen are eligible provided the response was greater than 12 months prior to study entry * 18 and over * ECOG Performance Status 0-2 * Bilirubin no greater than 2 mg/dL (unless secondary to tumor, hemolysis, or Gilbert syndrome) * Creatinine no greater than 2.0 mg/dL * Creatinine clearance ≥ 30 mL/min * Negative pregnancy test * Fertile patients must use 2 methods of effective contraception (including 1 barrier method) for at least 28 days before starting lenalidomide, while participating in the study, and for at least 28 days after discontinuation/stopping lenalidomide * At least 8 weeks since prior rituximab * At least 6 weeks since prior chemotherapy * At least 1 year since prior pentostatin, cyclophosphamide, and rituximab (PCR) therapy * PCR therapy at least 1 year prior to study entry allowed Exclusion criteria: * Bone marrow dysplasia related to prior therapy * New York Heart Association class III or IV heart failure * Prior lenalidomide * Other malignancy within the past 2 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix * Pregnant or nursing * Concurrent oral or IV antibiotics for active infection
are designated in this study