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.
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: 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
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Decitabine
DrugGiven PO
Decitabine and Cedazuridine
DrugGiven PO
Filgrastim
Biological/VaccineGiven SC or IV
Imaging Procedure
Procedure/SurgeryUndergo diagnostic imaging
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Maximum tolerated dose of ASTX727
Defined as maximum dose at which fewer than one-third of patients experience dose limiting toxicity.
Incidence of adverse events of ASTX727
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 ASTX727
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 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.
Incidence of graft versus host disease of ASTX727
Frequency of graft versus host disease stratified by dose level.
Severity of graft versus host disease of ASTX727
Frequency of graft versus host disease severity score stratified by dose level.
Incidence of graft rejection of ASTX727
Frequency of graft rejection stratified by dose level.
Severity of graft rejection of ASTX727
Frequency of graft rejection severity score by dose level.
Pharmacodynamic profile of ASTX727
Assessed through deoxyribonucleic acid methylation assay.
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