A Phase 1 Study of Oral Cedazuridine and Decitabine Combination (ASTX727, NSC# 820631) and Filgrastim as Maintenance Therapy Post-Hematopoietic Stem Cell Transplant in Children With High-Risk Acute Myeloid Leukemia
National Cancer Institute (NCI)
Summary
This phase I trial tests the safety, side effects, and best dose of ASTX727 and filgrastim for the treatment of children with high risk acute myeloid leukemia that has come back after a period of improvement (recurrent) or that does not respond to treatment (refractory) who have undergone allogenic hematopoietic stem cell transplantation. ASTX727 is a combination of cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Filgrastim stimulates the production of neutrophils (a type of white blood cell) which can help to prevent infection. Giving ATSX727 and filgrastim may be safe and tolerable in treating children with high risk, recurrent or refractory acute myeloid leukemia who have undergone allogenic hematopoietic stem cell transplantation.
Description
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…