Lenalidomide and Rituximab in the Treatment of Relapsed Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma

Inclusion Criteria:

1. Phase I and Phase II: Confirmed diagnosis of mantle cell lymphoma with CD20 positivity in tissue biopsy. Patients must have previously treated relapsed and/or refractory MCL. Or for Phase II: Confirmed diagnosis of previously treated relapsed and/or refractory diffuse large B-cell lymphoma, transformed large cell lymphoma, and/or Grade 3 follicular lymphoma (follicular cleaved large cell lymphoma or follicular non-cleaved large cell lymphoma).
2. Understand and voluntarily sign an Institutional Review Board (IRB) approved informed consent form.
3. Age equal to or greater than 18 years at the time of signing the informed consent.
4. Patients must have bi-dimensional measurable disease (bone marrow only involvement is acceptable).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
6. Serum bilirubin \<1.5 mg/dl and serum creatinine \< 2.0 mg/dl; platelet count \>75,000/mm\^3 and absolute neutrophil count (ANC) \> 1,000/mm\^3. AST (SGOT) and ALT (SGPT) \< 2 x upper limit of normal or \< 5 x upper limit of normal if hepatic metastases are present.
7. Disease free of prior malignancies of equal to or greater than 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy \> 3 years.
8. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test 10-14 days prior to therapy and repeated within 24 hours of starting study drug and must either commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide.
9. Continuation from # 8 : (HIGHLY EFFECTIVE METHODS - Intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation, partner's vasectomy. ADDITIONAL EFFECTIVE METHOD-latex condom, diaphragm, cervical cap) while on study drug.
10. WCBP must agree to have pregnancy tests every week for the first 4 weeks of treatment, then every 4 weeks if her menstrual cycles are regular or every 2 weeks if her cycles are irregular, while on study drug, and 4 weeks after the last dose of study drug. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
11. Patients may have 1 to 4 lines of prior therapy for MCL (projected median 2 prior lines of therapy). Patient may or may not have received an anthracycline-based chemotherapy regimen.
12. Patients must be willing to receive transfusions of blood products.
13. Past stem cell (autologous or allogenic) transplantation is acceptable.
14. Patients may have prior therapy with rituximab.

Exclusion Criteria:

1. Any serious medical condition including but not limited to, uncontrolled hypertension, diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active infection, active hemorrhage, laboratory abnormality, or psychiatric illness that places the patient at unacceptable risk and would prevent the subject from signing the informed consent form. Patients with history of cardiac arrythmias should have cardiac evaluation and clearance.
2. Pregnant or lactating females.
3. Use of any standard/experimental anti-lymphoma drug therapy, including steroids, within 3 weeks of initiation of the study or use of any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the study drug treatment.
4. Known hypersensitivity to thalidomide or rituximab; including the development of erythema nodosum if characterized by a desquamating rash while taking thalidomide.
5. Prior use of lenalidomide.
6. Known HIV infection. Patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; not including patients with positive serum Hepatitis B antibody). Known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation.
7. All patients with history of central nervous system lymphoma.
8. Patients with peripheral blood involvement with white blood cell count (WBC) \> 20,000 are EXCLUDED for the Phase I component of the study.
9. Patients with \>/= Grade 3 neuropathy.
10. Patients with active pulmonary embolism or deep vein thrombosis (30 days within diagnosis).
11. Patients with severe bradycardia (heart rate \<40 bpm, hypotension, light-headedness, syncope).