AzTrials
AzTrials

Acute Myeloid Leukemia Post Cytotoxic TherapyPhase 1NCT07012044

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 testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Acute Myeloid Leukemia Post Cytotoxic Therapy and Recurrent Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 15 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
15 sitesUnited States
Study dates
9 Jun 2026to 31 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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
  • STEP 0: Patients must not have received prior exposure to ASTX727. Note that patients may have had prior exposure to decitabine
  • STEP 1: Patient must be ≤ 21 years of age at the time of study enrollment to step 0 and step 1
  • STEP 1: Patients must have a body surface area ≥ 1m^2 at enrollment to step 1
  • STEP 1 (PRE-HCT): AML must be in complete remission (COG-CR, COG-CRp, COG-Cri), with or without detectable MRD; bone marrow CR must be assessed by central flow cytometry performed at Hematologics. Disease assessment must be performed within 14 days prior to the start of HCT conditioning regimen
  • Patients with CNS or extramedullary disease within 14 days prior to the start of the HCT condition regimen are not eligible
  • 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
  • Patients with CNS or extramedullary disease post-HCT are not eligible
  • 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)
  • Note: Estimated GFR (eGFR) from cystatin C or other estimates not listed above are not acceptable for determining eligibility
  • STEP 1: Bilirubin (total or sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • STEP 1: Alanine aminotransferase (ALT) ≤ 3 x ULN
  • STEP 1: Aspartate aminotransferase (AST) ≤ 3 x ULN
  • STEP 1: Albumin ≥ 2 g/dL

Who cannot join

  • 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
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  • 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
  • STEP 1: Idiopathic pneumonitis syndrome or other non-infectious lung injury requiring ongoing treatment (corticosteroids, tumor necrosis factor [TNF] inhibitors, or other biologics) or supplemental oxygen are not eligible
  • STEP 1: Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Trial locations and contacts

15 sites in 1 country. Contact the study team or a site near you to ask about taking part.

15 sites in 1 country

United States15 sites, 15 recruiting

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

    Site Public Contact, 800-865-1125

    Rajen Mody

    Recruiting

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

    Site Public Contact, 404-785-0232, Olivia.Floyd@choa.org

    Jason R. Fangusaro

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

    Site Public Contact, 303-764-5056, josh.b.gordon@nsmtp.kp.org

    Margaret E. Macy

    Recruiting

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

    Site Public Contact, 205-638-9285, oncologyresearch@peds.uab.edu

    Girish Dhall

    Recruiting

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

    Site Public Contact, 773-880-4562

    Sonali Chaudhury

    Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

    Site Public Contact, 513-636-2799, cancer@cchmc.org

    Joseph G. Pressey

    Recruiting

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

    Site Public Contact, 713-798-1354, burton@bcm.edu

    Jennifer H. Foster

    Recruiting

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

    Site Public Contact, 800-248-1199

    Brian D. Weiss

    Not yet recruiting

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

    Site Public Contact, 888-226-4343, referralinfo@stjude.org

    Jessica Gartrell

    Recruiting

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

    Site Public Contact, 612-624-2620

    Robin L. Williams

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Site Public Contact, 212-639-7592

    Maria Luisa Sulis

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Site Public Contact, 267-425-5544, CancerTrials@email.chop.edu

    Sarah K. Tasian

    Recruiting

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

    Site Public Contact, 412-692-8570, jean.tersak@chp.edu

    Archana Ramgopal

    Recruiting

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

    Site Public Contact, 877-827-3222, cancertrials@ucsf.edu

    Kieuhoa T. Vo

    Recruiting

  • Seattle Children's Hospital

    Seattle, Washington, 98105

    Site Public Contact, 866-987-2000

    Katherine G. Tarlock

    Recruiting

Other trials in United States

About this study

Official title: 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

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 when taken by mouth, 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 works in synergy with decitabine and enhances its activity. 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Decitabine, Decitabine and Cedazuridine
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • DecitabineDrug

    Also called 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine

    Given PO

  • Decitabine and CedazuridineDrug

    Also called ASTX 727, ASTX-727, ASTX727, C-DEC

    Given PO

  • FilgrastimBiological

    Also called Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi

    Given SC or IV

  • Imaging ProcedureProcedure or surgery

    Also called Diagnostic Imaging Technique, Image Type, Imaging, Imaging (procedure)

    Undergo diagnostic imaging

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

Study groups in NCT07012044
Study groupRoleWhat they receive
Treatment (ASTX727, diecitabine, filgrastim)ExperimentalPatients receive filgrastim SC or IV 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose of ASTX727

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

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

  2. Incidence of adverse events of ASTX727

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

    Measured: Up to 2 years

  3. Area under the concentration by time curve of ASTX727

    Median area under the concentration over time curve assessed at 1 and 3 hours post dose in cycle 1 stratified by dose level.

    Measured: Up to 28 days

  4. Half life of ASTX727

    Median half-life of ASTX727 stratified by dose level assessed at 1 and 3 hours post dose in cycle 1 stratified by dose level.

    Measured: Up to 28 days

  5. Clearance of ASTX727

    Median clearance of ASTX727 assessed at 1 and 3 hours post dose in cycle 1 stratified by dose level.

    Measured: Up to 28 days

Secondary outcomes (5)

  1. Incidence of graft versus host disease of ASTX727

    Frequency of graft versus host disease stratified by dose level.

    Measured: Up to 2 years

  2. Severity of graft versus host disease of ASTX727

    Frequency of graft versus host disease severity score stratified by dose level.

    Measured: Up to 2 years

  3. Incidence of graft rejection of ASTX727

    Frequency of graft rejection stratified by dose level.

    Measured: Up to 2 years

  4. Severity of graft rejection of ASTX727

    Frequency of graft rejection severity score by dose level.

    Measured: Up to 2 years

  5. Event free survival of ASTX727

    Median time to event stratified by dose level.

    Measured: At 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2025
  2. Study start9 Jun 2026
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07012044
Sponsor's protocol ID
NCI-2025-03946
Other IDs
NCI-2025-03946, PEPN2413, PEPN2413, UM1CA228823
Status last verified
Jun 2026
First submitted
7 Jun 2025
Last updated
23 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Acute Myeloid Leukemia Post Cytotoxic Therapy and Recurrent Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of ASTX727 (time frame: Up to completion of cycle 2 (cycle length=28 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07012044.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2026.

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