A Study to Find the Highest Dose of Cedazuridine and Decitabine Combination With Filgrastim as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With High-Risk Acute Myeloid Leukemia

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose and/or recommended phase 2 dose (RP2D) of decitabine and cedazuridine (ASTX727) administered together with filgrastim (rh-granulocyte colony stimulating factor \[GCSF\]) post-hematopoietic stem cell transplant (HCT) to children with high-risk acute myeloid leukemia (AML). II. To define and describe the toxicities of ASTX727 administered together with filgrastim (rh-GCSF) post-HCT in children with high-risk AML. III. To characterize the pharmacokinetic profile of ASTX727 administered together with filgrastim (rh-GCSF) post-HCT in children with high-risk AML. SECONDARY OBJECTIVES: I. To determine the incidence and severity of graft versus host disease and graft rejection in children with high-risk AML who received post-HCT therapy with ASTX727 and filgrastim (rh-GCSF). II. To preliminarily describe the 1-year event free survival (EFS) of patients with AML who received post-HCT therapy with ASTX727 and filgrastim (rh-GCSF), within the confines of a phase 1 study. EXPLORATORY OBJECTIVE: I. To characterize the pharmacodynamic profile of ASTX727 through deoxyribonucleic acid (DNA) methylation assay and, in turn, the potential impact of hypomethylation on donor immune cells and the graft versus leukemia effect. OUTLINE: This is a dose-escalation study of decitabine in combination with cedazuridine and filgrastim. Patients receive filgrastim subcutaneously (SC) or intravenously (IV) once daily (QD) on days 1-6 and ASTX727 orally (PO) QD on days 2-6. Patients may receive decitabine (with no cedazuridine) PO QD on days 2-6 to achieve the appropriate dose. Cycles repeat every 28 days up to12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study and may undergo lumbar puncture and diagnostic imaging throughout the study. After completion of study treatment, patients are followed up at 1 year post transplant and/or at relapse.