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

NCT07012044 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2025-03946PEPN2413UM1CA228823
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose

  Defined as maximum dose at which fewer than one-third of patients experience dose limiting toxicity.

  Up to completion of cycle 2 (cycle length=28 days)

• Incidence of adverse events

  Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Up to 2 years

• Pharmacokinetic profile of ASTX727

  Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  At cycle 1 last day of dosing

Secondary Outcomes (5)

• Incidence of graft versus host disease

  Up to 2 years

• Severity of graft versus host disease

  Up to 2 years

• Incidence of graft rejection

  Up to 2 years

• Severity of graft rejection

  Up to 2 years

• Event free survival

  At 1 year

Other Outcomes (1)

• Pharmacodynamic profile of ASTX727

  At cycle 1 day 1 and cycle 1 day 8

Study Arms (1)

Treatment (ASTX727, diecitabine, filgrastim)

EXPERIMENTAL

Patients receive filgrastim SC or IV QD on days 1-6 and ASTX727 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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Decitabine; Drug: Decitabine and Cedazuridine; Biological: Filgrastim; Procedure: Imaging Procedure; Procedure: Lumbar Puncture

Interventions

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (ASTX727, diecitabine, filgrastim)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (ASTX727, diecitabine, filgrastim)

Decitabine and Cedazuridine DRUG

Given PO

Also known as: ASTX 727, ASTX-727, ASTX727, C-DEC, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, DEC-C, Inaqovi, Inqovi

Treatment (ASTX727, diecitabine, filgrastim)

Filgrastim BIOLOGICAL

Given SC or IV

Also known as: Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi, Filgrastim-ayow, Filgrastim-sndz, G-CSF, Granix, Neupogen, Neutroval, Nivestim, Nivestym, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, Releuko, rG-CSF, Tbo-filgrastim, Tevagrastim, XM02, Zarxio

Treatment (ASTX727, diecitabine, filgrastim)

Imaging Procedure PROCEDURE

Undergo diagnostic imaging

Also known as: Diagnostic Imaging Technique, Image Type, Imaging, Imaging (procedure), Imaging Procedures, Imaging Technique, imaging type, IMAGING_METHOD, imaging_type, Medical Imaging, Type of imaging

Treatment (ASTX727, diecitabine, filgrastim)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (ASTX727, diecitabine, filgrastim)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (ASTX727, diecitabine, filgrastim)

Decitabine DRUG

Given PO

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (ASTX727, diecitabine, filgrastim)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• STEP 0: Patients with newly diagnosed high risk\* de novo AML, newly diagnosed therapy-related AML, relapsed, or refractory AML. in complete remission at the time of transplant. Patients with a history of isolated or combined central nervous system (CNS) or extramedullary disease are eligible if they have no evidence of active CNS or extramedullary disease at the time of trial enrollment (Step 0) and treatment enrollment (Step 1). Eligible patients with histories of isolated or combined CNS or extramedullary disease at time of relapse are required to be in complete remission at time of transplant to be eligible for this 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.
• No history of highly active antiretroviral therapy (HAART)-resistant HIV
• STEP 0: Patients must be receiving an allogeneic (related, unrelated, and mismatched related, including haploidentical) marrow, peripheral blood, or cord blood transplant for the first time
• STEP 0: HCT conditioning regimen must be planned to begin within 14 days after bone marrow assessment to determine disease status
• STEP 0: Conditioning regimen must be myeloablative and include high dose busulfan, or treosulfan, or total body irradiation

You may not qualify if:

• STEP 0: Patients with known inherited marrow failure syndromes, including, but not limited to Fanconi Anemia, Dyskeratosis congenita, and Shwachman-Diamond syndrome
• STEP 0: Known or suspected hypersensitivity to filgrastim, decitabine or cedazuridine (ASTX727)
• STEP 0: Patients who have received a prior solid organ transplantation are not eligible
• STEP 1: ASTX727 can cause fetal harm when administered to pregnant women. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Women of childbearing potential must use highly effective contraception during treatment with ASTX727 and for at least 6 months after the last dose. Men with female partners of childbearing potential should be advised to practice highly effective contraceptive measures of birth control and not to father a child while receiving treatment with decitabine and for 3 months after the last dose. Breastfeeding is not allowed during the study and for at least 2 weeks after the last dose of study drug
• STEP 1: Patients who are currently receiving another investigational drug are not eligible
• STEP 1: Patients who are currently receiving other anti-cancer agents are not eligible. Patients receiving intrathecal chemotherapy in the prior 14 days are eligible
• STEP 1: Patients receiving or for whom there is a plan to administer anticancer non-protocol therapy, radiation therapy or immunotherapy during the study period are not eligible (note that prophylactic use of chemotherapeutic agents for graft versus host disease \[GVHD\] is allowed, e.g. methotrexate for GVHD prophylaxis). Intrathecal cytarabine administered at the discretion of the treating physician throughout maintenance therapy is allowed
• STEP 1: Drugs known to be metabolized by cytidine deaminase (CDA) should not be given (such drugs include cytarabine, gemcitabine, azacitidine, vidarabine, zalcitabine, zidovudine, telbivudine, didanosine, stavudine, lamivudine, abacavir, emtricitabine, entecavir, trifluridine, tenofovir and adefovir) on days when ASTX727 is administered and for 24 hours thereafter
• STEP 1: Patients is not able to swallow intact tablets. Nasogastric or G tube administration is not allowed
• STEP 1: Patient is not able to start ASTX727 and filgrastim (rh-GCSF) between day 42 and day 100 following completion of allo-HCT. If, after enrollment, protocol therapy is started more than 100 days following allo-HCT, the patient will be removed from protocol therapy
• STEP 1: Patients with graft loss are not eligible
• STEP 1: Patients with steroid refractory or dependent acute GVHD are not eligible. Patients must be on \< 1 mg/kg/day of methylprednisolone (or equivalent prednisone/prednisolone dose) that is being tapered. Patients must not be on any second line systemic therapies. Continued GVHD prophylaxis with calcineurin inhibitors, sirolimus, abatacept or mycophenolate mofetil is acceptable
• STEP 1: Patients who have an uncontrolled viral, bacterial, fungal, or protozoal infection are not eligible
• STEP 1: Patients with active transplant associated thrombotic microangiopathy with ongoing hemolysis and need treatment (e.g. eculizumab) are not eligible
• STEP 1: Patients with sinusoidal obstruction syndrome with ongoing need for treatment (e.g. defibrotide, diuresis, supplemental oxygen) are not eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Specimen Handling; Biopsy; Decitabine; Injections; decitabine and cedazuridine drug combination; Filgrastim; Granulocyte Colony-Stimulating Factor; X-Rays; Spinal Puncture

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Diagnostic Techniques, Neurological; Punctures

Study Officials

• Maria Luisa Sulis

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2025
• First Posted: June 10, 2025
• Study Start (Estimated): July 26, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (2)