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A Phase 2 Study Evaluating the Efficacy of Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and Marginal Zone Lymphoma

Phase 2
18 Years
Open (Enrolling)
Follicular Lymphoma, Marginal Zone Lymphoma

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Trial Information

A Phase 2 Study Evaluating the Efficacy of Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and 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

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

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall lymphoma response rate, according to the International Workshop Criteria

Outcome Description:

A bayesian approach will be used to develop a gene expression profile for cell lines that respond to single agent azacitidine and to single agent lenalidomide. Samples from patients will then be assessed to see if they fit into likely responders versus non-responders based on their gene expressions. We will then assess whether the patients who responded to either of the two drugs were classified as responders using the gene expression profile developed in lymphoma cell lines. The chi-square tests will be used to test for association between predicted response and true response to an agent. The overall response (partial plus complete response) rate to single agent azacitidine, single agent lenalidomide and the combination as defined by the Cheson criteria.

Outcome Time Frame:

Within 4 months of taking single agent and 6 months of taking the combination

Safety Issue:


Principal Investigator

Anne W. Beaven, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University Medical Center Durham, NC USA


United States: Institutional Review Board

Study ID:




Start Date:

April 2010

Completion Date:

May 2015

Related Keywords:

  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • relapsed
  • refractory
  • lymphoma
  • follicular
  • marginal zone
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, B-Cell, Marginal Zone



Duke University Medical CenterDurham, North Carolina  27710