This phase II trial studies how well enasidenib and azacitidine work in treating patients with IDH2 gene mutation and acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). Enasidenib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Patients with AML or biphenotypic or bilineage leukemia (including a myeloid component) who have failed prior therapy. Patients with isolated extramedullary AML are eligible. The World Health Organization (WHO) classification will be used for AML
Elderly (> 60 years old) patients with newly diagnosed AML not eligible for intensive chemotherapy are also eligible
AML patients with prior history of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) regardless of prior therapy received, are eligible at the time of diagnosis of AML
Subjects must have documented IDH2 gene mutation
Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML)
Active and uncontrolled comorbidities including active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician
Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
Pregnant or breastfeeding
Single group
Azacitidine
DrugGiven SC or IV
Enasidenib Mesylate
DrugGiven PO
Overall response rate (ORR)
The study will estimate the ORR for the combination treatment, along with the Bayesian 95% credible interval. ORR will be defined as the proportion of patients who had CR (complete remission), CRh (complete remission with incomplete hematologic recovery), CRi (complete remission with incomplete count recovery), PR (partial response), and/or marrow clearance of blasts (MLFS).
Event-free survival
Kaplan-Meier method will be used to estimate the probabilities of event-free survival.
Overall survival (OS)
Kaplan-Meier method will be used to estimate the probabilities of overall survival.
Disease-free survival (DFS)
Log-rank tests will be used to compare among subgroups of patients in terms of DFS or OS.
Duration of response
Log-rank tests will be used.
Minimal residual disease (MRD)
MRD negative status and exploratory biomarkers will be summarized graphically and with descriptive statistics.
Association of biomarkers to overall response
Association between molecular and cellular markers and overall response and/or resistance assessed through logistic regression analyses.
Change in markers over time
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
