Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Patients With an IDH2 Mutation

PRIMARY OBJECTIVES: I. To determine the safety of treatment with enasidenib mesylate (enasidenib) administered at continuous daily oral dosing for a 28-day cycle up to 12 cycles in pediatric patients with IDH2-mutant relapsed/refractory (R/R)-acute myeloid leukemia (AML). II. To characterize the plasma pharmacokinetic (PK) profile of enasidenib in pediatric patients with IDH2-mutant R/R-AML. SECONDARY OBJECTIVES: I. To investigate the pharmacodynamic (PD) relationship of oncogenic metabolite 2-hydroxyglutarate (2-HG) to enasidenib treatment in pediatric patients with IDH2-mutant R/R-AML. II. To describe the clinical activity of enasidenib in pediatric patients with IDH2-mutant R/R-AML. IIa. Clinical activity will be defined as: IIai. Overall response rate (ORR) using response criteria adapted from the AML International Working Group Criteria; IIaii. Composite complete remission rate (CCRR) defined as complete remission (CR) and complete remission with incomplete blood count recovery (CRi); IIaiii. Time to response (TTR); IIaiv. Time to complete remission (TTCR); IIav. Duration of response (DOR); IIavi. Duration of CR (DOCR); IIavii. Event-free survival (EFS) and overall survival (OS). OUTLINE: Patients receive enasidenib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and/or biopsy and collection of blood on study. After completion of study treatment, patients are followed up at 30 days, then periodically up to 1 year.