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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 | Clinical Trials | Clareo Health

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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

NCT07012044•National Cancer Institute (NCI)

View on ClinicalTrials.gov

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.

Eligibility

Age

0 - 21 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•STEP 0: Patient must be ≤ 21 years of age
•* PLEASE NOTE: Eligibility criteria to enroll onto Step 1 for the treatment trial is ≤ 21 years of age at the time of Step 1 enrollment. Please plan accordingly to ensure that patients who are screened with Step 0 will be at an eligible age at the time of enrollment onto Step 1. Patients who are 21 at the time of screening who turn 22 at the time of enrollment onto Step 1 will not be eligible to enroll onto the study
•* Based on risk criteria adopted by the AAML1831 study
•STEP 0: Patient must plan to have bone marrow sample submitted to Hematologics within 14 days prior to the start of conditioning regimen for HCT.
•* Note: In order to be eligible to enroll onto Step 1 to receive treatment on this study, pre-HCT disease status must be assessed prior to receiving HCT. AML must be in complete remission (Children's Oncology Group \[COG\]-complete remission \[CR\], COG-complete remission with partial recovery of platelelt count \[CRp\], COG-complete remission with incomplete blood count recovery \[Cri\], with or without detectable minimal residual disease \[MRD\]); bone marrow CR must be assessed by central flow cytometry performed at Hematologics prior to the start of the conditioning regimen
•STEP 0: Human immunodeficiency virus (HIV)-infected patients are eligible for this trial if the following criteria are met:
•* No history of HIV complications with the exception of CD4 count \< 200cells/mm\^3
•* No antiretroviral therapy with overlapping toxicity such as myelosuppression
•* CD4 count \> 500 cells/mm\^3 prior to the diagnosis of newly diagnosed, relapsed, refractory AML.
•* HIV viral loads below the limit of detection within 6 months, as long as the patient is NOT receiving anti-retroviral agents that may interact with ASTX727.
+8 more criteria

Exclusion Criteria

•STEP 1 (POST-HCT): AML must be in complete remission (COG-CR, COG-CRp, COG-CRi). Bone marrow evaluation must show CR with no detectable minimal residual disease (MRD negative by central flow cytometry at Hematologics)
•* Note: Disease assessment is required to be performed within 14 days prior to enrollment onto Step 1
•STEP 1: Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age. Patients must have Karnofsky performance score ≥ 50 or Lansky play-performance scale score ≥ 50
•STEP 1: Patients must have fully recovered from the acute toxicities related to the conditioning regimen and the transplant. If, after 42-100 days post-transplant, the eligibility criteria are met, the patient is considered to have recovered adequately
•STEP 1: Platelet count ≥ 50,000 µL (without requirement for platelet transfusion within the last 7 days)
•STEP 1: Hemoglobin ≥ 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions)
•STEP 1: Absolute neutrophil count ≥ 1,000 µL with no myeloid growth factor support within the last 3 days
•Estimated glomerular filtration rate (GFR) (eGFR) ≥ 60 mL/min/1.73 m\^2 "Bedside" Schwartz formula (2009) OR
•* OR- A 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m\^2
•* A GFR ≥ 60 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
+11 more criteria

Key Dates

Start Date

October 30, 2026

Primary Completion Date

January 1, 2027

Completion Date

January 1, 2027

Last Updated

March 20, 2026

Enrollment

ESTIMATED participants

Conditions

Acute Myeloid Leukemia Post Cytotoxic TherapyRecurrent Acute Myeloid LeukemiaRefractory Acute Myeloid Leukemia

Interventions

Biospecimen Collection

PROCEDURE

Bone Marrow Aspiration

PROCEDURE

Bone Marrow Biopsy

PROCEDURE

Decitabine

DRUG

Decitabine and Cedazuridine

DRUG

Filgrastim

BIOLOGICAL

Imaging Procedure

PROCEDURE

Lumbar Puncture

PROCEDURE

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 20, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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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

Inclusion Criteria

Exclusion Criteria

Testing the Anti-cancer Drug, Cirtuvivint, and Its Combination With ASTX727 to Improve Outcomes in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes

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