Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and Marginal Zone Lymphoma
Condition: Follicular Lymphoma; Marginal Zone Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone
Intervention: azacitidine; lenalidomide
Intervention description: Azacitidine 75 mg/m2 SC or IV on days 1-5; subjects will begin Part 2 at the azacitidine dose level tolerated in Part 1a.; Lenalidomide dose is 15mg po per day on days 1-21; starting dose during Part 2 will depend upon how well the subject tolerated drug during Part 1.
Intervention MeSH terms: Lenalidomide; Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: relapsed; refractory; lymphoma; follicular; marginal zone

Summary:

      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.
    

Eligibility criteria:

        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