Seclidemstat and Azacitidine for the Treatment of Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

PRIMARY OBJECTIVES: I. To determine the safety, tolerability and maximum tolerable dose (MTD) of seclidemstat in combination with azacitidine. II. To assess overall response rate (ORR) to seclidemstat in combination with azacitidine. SECONDARY OBJECTIVES: I. To assess overall survival (OS), duration of response (DOR), relapse-free survival (RFS), and leukemia-free survival (LFS) and safety profile. II. Correlative studies including correlation of response with disease subtypes, genomic profile and in vitro studies. OUTLINE: This is a phase I, dose-escalation study of seclidemstat followed by a phase II dose-expansion study. Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7. Patients also receive seclidemstat orally (PO) once daily (QD) on day 1 of cycle 1 and PO twice daily (BID) on days 2-28 of cycle 1 and on days 1-28 of all subsequent cycles. There are 6 possbile dose levels for seclidemstat: 300 mg, 450 mg, 600 mg, 900 mg, 1200 mg and 1500 mg. Successive cohorts of eligible patients will be treated with azacitidine until the phase 2 recommended dose or maximum tolerated dose is determined. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days, and then every 6 months thereafter