This phase II trial studies the side effects and how well azacitidine and enasidenib work in treating patients with IDH2-mutant myelodysplastic syndrome. Azacitidine and enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Signed, informed consent must be obtained prior to any study specific procedures
Subjects with a histologically confirmed diagnosis of MDS, including both MDS and refractory anemia with excess blasts in transformation (RAEB-T) (acute myeloid leukemia [AML] with 20-30% blasts and multilineage dysplasia by French-American-British [FAB] criteria) by World Health Organization (WHO), and chronic myelomonocytic leukemia (CMML) are eligible
Subjects must have an IDH2 gene mutation (IDH2-R140 or R172) as determined by local laboratory result
(Arm A only): Subject must be hypomethylating agent naive (i.e. prior azacitidine, decitabine, SGI-110 is exclusionary). Receipt of other MDS-directed therapy such as lenalidomide is allowed
Any prior or coexisting medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
Subject has received a prior targeted IDH2 inhibitor
Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
Active uncontrolled infection at study enrollment including known diagnosis of human immunodeficiency virus or chronic active hepatitis B or C infection
Parallel
Azacitidine
DrugGiven IV or SC
Enasidenib
DrugGiven PO
Quality-of-Life Assessment
Other interventionAncillary studies
Incidence of adverse events
Will use the Bayesian method by Thall, Simon and Estey for toxicity monitoring. For purpose of toxicity monitoring, toxicity is defined as any grade 3 or higher treatment related-toxicities by Common Terminology Criteria for Adverse Events criteria.
Overall response rate
Defined as complete response (CR), partial response, and marrow CR assessed by International Working Group criteria. Will be estimated along with the 90% credible interval.
Event-free survival (EFS)
The Kaplan-Meier method will be used to estimate the probabilities of EFS. Log-rank tests will be used to compare among subgroups of patients in terms of EFS.
Overall survival (OS)
The Kaplan-Meier method will be used to estimate the probabilities of OS. Log-rank tests will be used to compare among subgroups of patients in terms of OS.
Anti-tumor activity
Will be summarized graphically and with descriptive statistics.
Pharmadynamics (PDn) markers
PDn markers will be summarized graphically and with descriptive statistics.
Biomarkers analysis
The association between molecular and cellular markers and overall response and/or resistance will be assessed through logistic regression analyses. Paired t-test or Wilcoxon signed rank test will be used to assess the marker change over time.
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M.D. Anderson Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Celgene
Collaborator
