Lenalidomide With or Without Rituximab After Standard Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma

Inclusion Criteria:

1. Understand and voluntarily sign an Informed Consent form
2. Age \> 18 years at time of signing the Informed Consent Form
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Patients with histological confirmation of diffuse large B cell lymphoma with at least one of the following characteristics:

   * High or intermediate IPI score (See Appendix 8.0 for IPI scoring criteria)
   * Patients who are still PET scan positive mid therapy with R-CHOP, but, have turned negative after completion of therapy.
   * Low risk International prognostic index ie., an IPI score of \<3 if age \>60 years or \<2 if age is less than or equal to 60 with c-myc positive by Fluorescent In situ Hybridization.
5. No other previous lymphoma therapy, hormonal therapy or surgery, except for standard therapy with R-CHOP with or without radiation and with or without prophylactic Methotrexate therapy. Patients must be enrolled within 4-12 weeks of completion of therapy.
6. At the time of study entry following standard therapy with R-CHOP±RT, patients should be in complete remission.
7. ECOG performance status of ≤ 2 at study entry
8. Laboratory test results within these ranges:

   * Absolute neutrophil count ≥ 1500/mm³
   * Platelet count ≥100K /mm³
   * Serum creatinine ≤ 2.0 mg/dL
   * Total bilirubin ≤ 1.5 mg/dL
   * AST (SGOT) and ALT (SGPT) ≤ 2 x ULN
9. Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell or 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® program, and be willing and able to comply with the requirements of the Revlimid REMS® program.

    •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 the Revlimid REMS® program) 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. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation, if patients are thought to be at an elevated risk of thrombosis.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the Informed Consent
2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
3. 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.
4. Use of any other experimental drug or therapy within 28 days of baseline.
5. Known hypersensitivity to thalidomide.
6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7. Any prior use of lenalidomide.
8. Concurrent use of other anti-cancer agents or treatments.
9. Known positive for HIV or infectious hepatitis, type B or C.
10. A diagnosis of deep vein thromboses in the preceding 3 months of study enrollment.