Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation

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PRIMARY OBJECTIVE: I. To determine the rate of complete response (CR) to olaparib using a composite CR endpoint (CR + CR with incomplete hematologic response [CRi] + CR with partial hematologic response [CRh]) in subjects with isocitrate dehydrogenase (IDH)1/2 mutant myelodysplastic syndrome (MDS) o...

PRIMARY OBJECTIVE: I. To determine the rate of complete response (CR) to olaparib using a composite CR endpoint (CR + CR with incomplete hematologic response [CRi] + CR with partial hematologic response [CRh]) in subjects with isocitrate dehydrogenase (IDH)1/2 mutant myelodysplastic syndrome (MDS) or IDH1/2-mutant acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR) to olaparib using a composite ORR endpoint (CR + morphologic leukemia-free state [MLFS] + partial response [PR]) in patients with IDH mutant AML or MDS treated with olaparib. II. To establish the progression free survival (PFS) of patients with IDH mutant AML or MDS treated with olaparib. III. To determine the overall survival (OS) of patients with IDH mutant AML or MDS treated with olaparib. IV. To establish the duration of response (DOR) to treatment with olaparib. V. To evaluate the safety and tolerability of olaparib in AML or MDS patients. EXPLORATORY OBJECTIVES: I. To establish a relationship between treatment response and correlative studies such as plasma and bone marrow 2-hydroxyglutarate (2HG) levels, and IDH variant allele frequency. II. To evaluate persistence of double strand breaks in IDH 1/2 mutant AML or MDS. III. To evaluate response to therapy in the different IDH mutant genotypes. IV. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), ribonucleic acid (RNA) sequencing (RNAseq) order to: IVa. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned. IVb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms. V. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. VI. To bank blood and bone marrow aspirate obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital. OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 90 days.

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