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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall lymphoma response rate, according to the International Workshop Criteria
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.
Within 4 months of taking single agent and 6 months of taking the combination
Anne W. Beaven, MD
Duke University Medical Center Durham, NC USA
United States: Institutional Review Board
|Duke University Medical Center||Durham, North Carolina 27710|