NCT07012044

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

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

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 47 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

Detailed 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 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 PO QD on days 2-6 to achieve the appropriate dose. Cycles repeat every 28 days for 12 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.

Conditions

• Acute Myeloid Leukemia Post Cytotoxic Therapy
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
DRUG	Decitabine	Given PO
DRUG	Decitabine and Cedazuridine	Given PO
BIOLOGICAL	Filgrastim	Given SC or IV
PROCEDURE	Imaging Procedure	Undergo diagnostic imaging
PROCEDURE	Lumbar Puncture	Undergo lumbar puncture

Timeline

• Start date: 2026-10-30
• Primary completion: 2027-01-01
• Completion: 2027-01-01
• First posted: 2025-06-10
• Last updated: 2026-04-13

Regulatory

• FDA-regulated drug study