Safety and Efficacy of Revlimid® (Lenalidomide) With Mabthera® (Rituximab) in Non-Hodgkin's Lymphoma

1. Age ≥ 18 years.
2. Diagnosis of relapsed or refractory to previous therapy biopsy-proven Diffuse Large B cell non-Hodgkin's Lymphoma (there is no limit on the number of prior therapies. Subjects who have relapsed following an autologous stem cell transplant are eligible.)
3. Measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter.
4. ECOG (Eastern Cooperative Oncology Group) performance status score of 0, 1, or 2.
5. Life expectancy of >= 90 days (3 months).
6. Must be able to adhere to the study visit schedule and other protocol requirements.
7. Signed informed consent
8. Social security program affiliation
9. Females of childbearing potential (FCBP*) must have negative pregnancy test (sensitivity of at least 25 mIU/mL) prior to starting study drug in accordance with the Global Pregnancy Prevention Plan (PPP, annex 6)
10. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously** or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study drug; and 3) for at least 12 months after discontinuation from the study drug.

Male Subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy.

Agree not to donate blood, semen or sperm while taking study drug and for 28 days after stopping study drug. Do not share drug with other person. Do not break, chew, or open study drug capsules. Return unused study drug capsules to the study doctor.

EXCLUSION criteria

1. Any of the following laboratory abnormalities:

   • Absolute neutrophil count (ANC) \< 1.5 x 109/L.
   • Platelet count \< 60 x 109/L.
   • Calculated creatinine clearance (Cockcroft-Gault formula) of \< 50mL/min.
   • Serum SGOT/AST or SGPT/ALT 5.0 x upper limit of normal (ULN).
   • Serum total bilirubin > 2.0 mg/dL (34 μmol/L)/conjugated bilirubin >0.8mg/dL, except in case of hemolytic anemia.
2. Subjects who are candidates for and willing to undergo an autologous stem cell transplant.
3. Subjects who are post allogenic stem cell transplant.
4. All subjects with active central nervous system (CNS) lymphoma. Subjects with previous CNS lymphoma that have been treated with chemotherapy, radiotherapy or surgery who have remained asymptomatic for 90 days (3 months) and demonstrate, no CNS lymphoma, as shown by lumbar puncture, CT scan or MRI, are eligible. (If required, lumbar puncture, CT or MRI should be performed during screening process.) Subjects should not be receiving corticosteroids.
5. Prior history of malignancies other than NHL (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for 5 years
6. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
7. Pregnant or lactating females.

8. Uncontrolled intercurrent illness including, but not limited to:

   • Ongoing, severe or active infection requiring antibiotics.
   • Uncontrolled diabetes mellitus as defined by the investigator.
   • Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease).
   • Unstable angina pectoris, angioplasty, stenting, or myocardial infarctions within 168 days (6 months).
   • Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia.
9. Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide.
10. Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide.
11. Subjects with ≥ Grade 2 neuropathy.
12. Prior use of lenalidomide.
13. Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy.
14. Known active Hepatitis B or C.
15. Known positive for HIV.
16. Known hypersensibility to Rituximab or excipients, or to murine proteins,
17. Patients with severe immune deficit