The study closed temporarily in February 2012 pending analysis of samples collected. In October, 2012, Celgene requested closure of the study.

The purpose of this study is to evaluate the response and safety in subjects receiving the drugs lenalidomide and azacitidine when each drug is given by itself and when the drugs are taken together. This study is open for patients with relapsed or refractory follicular or marginal zone lymphoma.

This will be a prospective, non-randomized, un-blinded, phase 2 efficacy trial using an Immunomodulatory derivatives of thalidomide (IMiD™)compound and a hypomethylating agent for epigenetic targeted therapies in patients with relapsed/refractory follicular and marginal zone lymphoma. There will be two parts to the trial. Each patient will progress through each part of the study.

Part 1: Sequential single agent therapy with azacitidine and lenalidomide. Each agent will be given for four-six 28-day cycles.

Subjects with less than a complete response (CR) after 4 cycles of study drug in Part 1a or 1b should proceed to the next study drug(s) after the prescribed washout period.

Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease.

There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. There will be no washout period required between Part 1 and Part 2.

Part 2: Combination therapy with azacitidine and lenalidomide given in 28-day cycle for up to 13 cycles in subjects who have stable disease or better.

Inclusion Criteria:

1. Histologically or cytologically confirmed Follicular or Marginal Zone Lymphoma

2. Refractory disease defined as persistence of evaluable disease after therapy or have relapsed disease to at least one prior treatment regimen

3. Understand and voluntarily sign an informed consent form

4. Age > or = to 18 years

5. Able to adhere to the study requirements

6. A frozen tumor sample must be available for microarray analysis. This may either be a previously collected sample if it was properly prepared or a new biopsy may be obtained.

   o At least 1 core biopsy specimen using at least a 16 gauge needle, which corresponds to roughly 25 mg of tissue. An equivalent amount of biopsy material from previously performed procedures, as long as it was fresh frozen, can be used. Sample obtained with leukapheresis is acceptable in subjects with a white blood cell count (WBC) of 100,000 or greater.

7. Eastern Cooperative Oncology Group (ECOG) performance status of < or = to 2

8. Laboratory test results within ranges specified by the protocol.

9. Disease free of prior malignancies for > or = to 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast or superficial melanoma only requiring excision or prostate cancer with a prostate specific antigen (PSA) that has not increased for at least 3 months.

10. All study participants must be willing to be registered into the mandatory RevAssist® program, and comply with the requirements of RevAssist®.

11. Females of childbearing potential (FCBP) must comply with pregnancy testing requirements. Men and women must use approved birth control methods during the study.

12. Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine.

13. If at high risk for thrombotic event (such as on steroids or history of deep vein thrombosis), subjects must be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid may use warfarin or low molecular weight heparin)

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
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 or mannitol.
6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
7. Any prior use of lenalidomide or azacitidine
8. Concurrent use of other anti-cancer agents or treatments
9. Known positive for HIV or infectious hepatitis, type B or C
10. No chemotherapy, biologics or immunotherapy within 2 weeks prior to registration as specified in the protocol. Subjects must have recovered from all therapy-related non-hematological toxicities to < grade 1 or to baseline if patient started with > grade 1 toxicity. There is no time limit with regards to radiation prior to registration.
11. No radioimmunotherapy within 2 months prior to registration. Subjects must have recovered from all therapy-related toxicities to < grade 1 or to baseline if patient started with > grade 1 toxicity.
12. No prior allogeneic stem cell transplantation unless allogeneic engraftment is <2%
13. Subjects receiving chronic, systemic treatment with corticosteroids equivalent to >20mg of prednisone per day

We collect adverse event information from the time they start drug until 30 days after the last dose.