Clinical Trial: Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and Marginal Zone Lymphoma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

Brief 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.

Detailed Summary:

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.


Sponsor: Duke University

Current Primary Outcome:

  • Response Predicted by Molecular Signatures Compared to True Response [ Time Frame: approximately one year ]
    The predicted response (response to therapy vs. no response to therapy) using gene sequencing will be compared to the overall "true" response (reported in Primary Outcome 2).
  • Overall Response [ Time Frame: Response will be assessed after at least 4 months on first study drug. ]

    Number of patients with a complete or partial response using Cheson criteria for lymphoma.

    A complete response is defined as a complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy. A partial response is defined as a greater than or equal to 50% decrease in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Patients who have been on study drug for at least 2 months will be considered evaluable for response as long as they have had repeat imaging to assess response or clear progression based on physical exam.

  • Overall Response [ Time Frame: Response will be assessed after at least 4 months on second drug. ]

    Number of patients with a complete or partial response using Cheson criteria for lymphoma.

    A complete response is defined as a complete disappearance of all detectable clinical and radiographic evidence of disease and di

    Original Primary Outcome: Overall lymphoma response rate, according to the International Workshop Criteria [ Time Frame: Within 4 months of taking single agent and 6 months of taking the combination ]

    Overall lymphoma response rate & assess whether a genomic molecular signature predictive of response to azacitidine in pre-clinical models is associated with a response to lenalidomide in patients with lymphoma.


    Current Secondary Outcome: Number of Participants With Grade 3 and 4 Toxicities [ Time Frame: While taking the study drug and 30 days after the last dose ]

    Evaluate the safety of lenalidomide, azacitidine and the combination of azacitidine + lenalidomide in patients with lymphoma; grading the adverse events using Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0


    Original Secondary Outcome: Evaluate the safety of lenalidomide, azacitidine and the combination of azacitidine + lenalidomide in patients with lymphoma; grading the adverse events using CTCAE version 4.0 [ Time Frame: every 2 weeks while taking study drug and every 3 months once all study drugs are completed ]

    Information By: Duke University

    Dates:
    Date Received: February 11, 2010
    Date Started: April 2010
    Date Completion:
    Last Updated: August 1, 2016
    Last Verified: August 2016