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
National Cancer Institute (NCI)
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.
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…
Eligibility
- Age range
- Up to 21 years
- Sex
- All
- Healthy volunteers
- No
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 * STEP 0: Patients with newly diagnosed high risk\* de novo AML, newly diagnosed therapy-related AML, relapsed,…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- DrugDecitabine
Given PO
- DrugDecitabine and Cedazuridine
Given PO
- BiologicalFilgrastim
Given SC or IV
- ProcedureImaging Procedure
Undergo diagnostic imaging
Locations (2)
- Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania
- Saint Jude Children's Research HospitalMemphis, Tennessee