Cedazuridine and Decitabine for High-Risk Childhood AML After Transplant
This study is testing a combination of two medicines, cedazuridine and decitabine (called ASTX727), along with filgrastim, in children up to 21 years old. These children have high-risk acute myeloid leukemia (AML) that has returned or hasn't responded to previous treatments, and they have already had a stem cell transplant. Cedazuridine helps decitabine work better by preventing its breakdown. Decitabine helps the body make healthy blood cells and kills abnormal cells. The main goal is to find the safest and most effective dose of ASTX727 and to understand its side effects and how it moves through the body. The study plans to enroll 47 participants, but its current status is unclear.
- Study design
- This is a dose-escalation study, meaning participants will receive increasing doses of the study drugs to find the best amount. It is an interventional study, which means participants will receive specific treatments as part of the research.
- What's involved
- You would undergo blood sample collection, bone marrow aspiration (removing a small amount of bone marrow), and bone marrow biopsy (removing a small piece of bone marrow). You would receive decitabine and cedazuridine by mouth.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will track side effects for up to two years and assess the drug's levels in the body on the last day of dosing in the first cycle.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
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
Recruiting
PHASE1Up to 21InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~47 participants
Updated 2026-08-20 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone Marrow AspirationBone Marrow BiopsyDecitabineDecitabine and CedazuridineFilgrastim
At a glance
Recruiting sites
11 of 11 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximum tolerated dose of ASTX727
Measured over Up to completion of cycle 2 (cycle length=28 days)
+4 more outcomes measured
Conditions
Where it's being run
11 sites across 10 statesPennsylvania2
Alabama1
Colorado1
Illinois1
Indiana1
Michigan1
Minnesota1
New York1
Study leadership
- Maria Luisa Sulis · PRINCIPAL_INVESTIGATOR · Pediatric Early Phase Clinical Trial Network
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
Exclusion
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
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
What this trial measures
- Maximum tolerated dose of ASTX727Up to completion of cycle 2 (cycle length=28 days)
Defined as maximum dose at which fewer than one-third of patients experience dose limiting toxicity.
- Incidence of adverse events of ASTX727Up to 2 years
Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- Area under the concentration by time curve of ASTX727Up to 28 days
Median area under the concentration over time curve assessed at 1 and 3 hours post dose in cycle 1 stratified by dose level.
- Half life of ASTX727Up to 28 days
Median half-life of ASTX727 stratified by dose level assessed at 1 and 3 hours post dose in cycle 1 stratified by dose level.
- Clearance of ASTX727Up to 28 days
Median clearance of ASTX727 assessed at 1 and 3 hours post dose in cycle 1 stratified by dose level.