Testing the Addition of an Anti-cancer Drug, M3814, to the Usual Treatment (Mitoxantrone, Etoposide, and Cytarabine) for Relapsed or Refractory Acute Myeloid Leukemia

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PRIMARY OBJECTIVES: I. To assess the safety and tolerability and determine the recommended phase two dose (RP2D) of M3814 in combination with mitoxantrone, etoposide, and cytarabine (MEC) in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To characte...

PRIMARY OBJECTIVES: I. To assess the safety and tolerability and determine the recommended phase two dose (RP2D) of M3814 in combination with mitoxantrone, etoposide, and cytarabine (MEC) in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To characterize the pharmacokinetic (PK) profile of MEC alone and of M3814 in combination with MEC. II. To evaluate the preliminary efficacy of M3814 in combination with MEC in patients with R/R AML as measured by the response rate (complete remission [CR] plus CR with incomplete count recovery), duration of CR/CRi (DOR), event-free survival (EFS) and overall survival (OS). EXPLORATORY OBJECTIVES: I. To evaluate correlative biomarkers of M3814 target engagement and response. II. To correlate cytogenetic and molecular abnormalities with response. III. To evaluate the rates of early mortality and allogeneic hematopoietic cell transplantation. IV. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in 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. OUTLINE: This is a dose-escalation study of M3814. Patients receive M3814 orally (PO) twice daily (BID) on days 2-21, mitoxantrone intravenously (IV) over 15 minutes, etoposide IV over 60 minutes and cytarabine IV over 60 minutes on days 1-5 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, then every 6 months thereafter.

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