Alternating Thalidomide and Lenalidomide Therapy Plus Rituximab (ThRiL) as Initial Treatment for Patients With CLL

Inclusion criteria: 1\. Confirmed diagnosis of CLL or SLL based upon standard criteria as outlined in the IWCLL Update of the 1996 NCI-Working Group criteria for CLL: a) Presence of one of the following: 1\. more than or equal to 5 x 10\^9 B lymphocytes/L in the peripheral blood for a duration of at least 3 months. Patients with a B lymphocytosis will be characterized as CLL, while those without will be characterized as SLL 2\. the presence of lymphadenopathy resulting from infiltration with lymphocytes with the phenotype of CLL 3\. bone marrow infiltration with lymphocytes with the phenotype of CLL b) Lymphocytes with the morphologic appearance of small, mature appearing lymphocytes, with less or equal to 55 percent prolymphocytes (blood or bone marrow) c) Cellular phenotype characterized by the: 1. co-expression of the CD5, CD20, and CD23 surface antigens 2. clonal kappa or lambda light chain expression 3. dim surface immunoglobulin expression 2\. No prior therapy for CLL, including treatment for autoimmune conditions that have developed since the initial diagnosis of CLL. 3\. Active disease requiring therapy as defined by the IWCLL Update of the 1996 NCIWG guidelines: 1. Evidence of progressive marrow failure as manifested by the development of worsening of anemia and / or thrombocytopenia 2. Massive, progressive, or symptomatic splenomegaly 3. Massive, progressive, or symptomatic lymphadenopathy 4. Progressive lymphocytosis with an increase of more than 50 percent over a 2-month period or a lymphocyte doubling time of less than 6 months. 5. Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy 6. Presence of disease related symptoms: unintentional weight loss of more than 10 percent within previous six months, significant fatigue, fevers greater than 100.5 F or 38.0 C for 2 or more weeks without evidence of infection, night sweats for more than 1 month without evidence of infection. 4\. Understand and voluntarily sign an informed consent form. 5\. Age at least 18 years at the time of signing the informed consent form. 6\. Able to adhere to the study visit schedule and other protocol requirements. 7\. ECOG performance status of at most 2 at study entry. 8\. Laboratory test results within these ranges: * Absolute neutrophil count at least 1000/mm³ * Platelet count at least 50,000/mm³ * Creatinine clearance of at least 30 mL/min by Cockroft-Gault formula. Patients with a baseline creatinine clearance of greater than 30 and less than 60 mL/min will have a starting dose of lenalidomide 5 mg PO every other day per the defined schedule. Patients with a baseline creatinine clearance of ≥ 60 mL/min will have a starting dose of lenalidomide 5 mg PO daily per the defined schedule. * Total bilirubin at most 1.5 times the ULN, unless abnormality is the result of Gilbert's disease or the result of the CLL. * AST (SGOT) and ALT (SGPT) at most 3 x ULN (or at most 5 x ULN if due to the CLL) 9\. Disease free of prior malignancies for at least 2 years with exception of curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. 10\. All study participants must be registered into the mandatory Revlimid REMS and S.T.E.P.S. ( P-TAP: Protocol Therapy Assistance Program) program(s), and be willing and able to comply with the requirements of Revlimid REMS and S.T.E.P.S. 11\. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 -14 days prior to and again within 24 hours of starting treatment and again within 24 hours before the first dose of lenalidomide AND thalidomide. FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide and/or thalidomide. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program . 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. 12\. Able to take aspirin 81 or 325 mg daily as prophylactic anticoagulation, unless already on therapeutic anticoagulation. Patients intolerant to ASA may use coumadin or low molecular weight heparin. Exclusion criteria: 1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent. 2. 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. 3. Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome. Subjects may be enrolled upon correction of electrolyte abnormalities. 4. Concurrent use of other anti-cancer agents or treatments. 5. Prior treatment with thalidomide or lenalidomide. 6. Active serious infection not controlled with antibiotics. 7. Autoimmune hemolytic anemia or thrombocytopenia requiring treatment. 8. Known positive for HIV 9. Active infection with hepatitis B, defined by being positive for HepBsAg or Hep B DNA by PCR, or hepatitis C 10. Pre-existing peripheral neuropathy greater than grade 2 11. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide and/or thalidomide).