Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Inclusion Criteria:

1. Histologically confirmed CLL/SLL.
2. Understand and voluntarily sign an informed consent document.
3. Age greater than or equal to 18 years at the time of signing the informed consent document.
4. Subjects must have documented relapsed or refractory CLL/SLL.

   * Relapsed disease is defined as progressive disease after achieving a complete or partial response to the most recent therapy.
   * Refractory disease is defined as less than a partial response to the most recent therapy.
5. Subjects must have received ≥1 prior chemotherapy regimen for their disease. Prior therapy with single-agent rituximab does not meet criteria for a prior chemotherapy regimen (i.e., prior treatment must include cytotoxic chemotherapy agent).
6. In cases of SLL, subjects must have at least one bidimensionally measurable lesion at least ≥1.5 cm measured in one dimension.
7. Eastern Cooperative Oncology Group performance status of less than or equal to 2 at study entry
8. Laboratory test results within these ranges:

   * Absolute neutrophil count greater than or equal to 1500/μL
   * Platelet count great than or equal to 100,000/μL
   * Subjects with neutrophils \<1500/μL or platelets \<100,000/μL with splenomegaly or extensive bone marrow involvement as the etiology for their cytopenias are eligible
   * Subjects must have adequate renal function with a creatinine clearance of ≥40 mL/min as determined by the Cockcroft-Gault calculation
   * Total bilirubin less than or equal to 2X (times) upper limit laboratory normal (ULN); subjects with non-clinically significant elevations of bilirubin due to Gilbert's disease are not required to meet these criteria
   * Serum transaminases aspartate aminotransferase (AST) (SGOT) and (alanine aminotransferase) ALT (SGPT) less than or equal to 5X ULN
   * Serum alkaline phosphatase ≤5X ULN
9. Disease-free of prior malignancies for ≥2 years with the exception of basal or squamous cell skin carcinoma, carcinoma "in situ" of the breast or cervix, or localized prostate cancer (treated definitively with hormone therapy, radiotherapy, or surgery).
10. Life expectancy of at least 3 months.
11. All study participants must be willing to be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS® .
12. Subjects must not have a known history of hypersensitivity to mannitol.
13. Subjects may have received prior therapy with bendamustine or lenalidomide, but must not have disease that is refractory to bendamustine or lenalidomide.
14. Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease.
15. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects intolerant to aspirin may use warfarin or low molecular weight heparin) if clinically indicated.
16. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by Revlimid REMS® ) and 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. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

15\. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.

Exclusion Criteria:

Subjects may not have received \>5 lines of prior therapy for their disease. Re-treatment with an identical regimen does not count as a new regimen.

2\. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document or complying with the protocol treatment.

3\. Pregnant or breast-feeding females. Lactating females must agree not to breast-feed while taking lenalidomide.

4\. 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.

5\. Subjects are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement.

6\. Use of any other experimental drug or therapy within 28 days of enrollment.

7\. Known hypersensitivity to thalidomide. 8. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

9\. Disease that is refractory to prior therapy with bendamustine or lenalidomide.

10\. Concurrent use of other anti-cancer agents or treatments. 11. Known to be positive for HIV or infectious hepatitis (type B or C). 12. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, or other cancer from which the subject has been disease free for at least 2 years.

13\. Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously exposed to rituximab or other monoclonal antibody therapy.

14\. Chronic hepatitis B or hepatitis C infection. 15. New York Heart Association class 3-4 heart failure.