This phase II trial evaluates the feasibility and effectiveness of decitabine given in combination with filgrastim post allogeneic hematopoietic cell transplant (HCT) in preventing or delaying the return (relapse) of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and treatment-related myeloid malignancies in pediatric and young adult patients. Approximately one-third of these patients will require HCT given the high-risk nature of their disease. Despite HCT, relapse remains a major cause of treatment failure. As such, new therapeutic approaches are needed. 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 is in a class of medications called colony-stimulating factors. It works by helping the body make more neutrophils. Giving decitabine in combination with filgrastim post-HCT may help decrease the risk of relapse in pediatric and young adult patients with AML, MDS, and treatment-related myeloid malignancies.
Additional locations may be listed on ClinicalTrials.gov for NCT05796570.
Locations matching your search criteria
United States
Massachusetts
Boston
Dana-Farber Cancer InstituteStatus: Active
Contact: Franziska Wachter
Phone: 617-632-3352ext49056
Boston Children's HospitalStatus: Active
Contact: Franziska Wachter
PRIMARY OBJECTIVE:
I. To assess the feasibility of post-transplant remission maintenance with decitabine and filgrastim in pediatric patients with acute myeloid leukemia, myelodysplastic syndrome, and treatment related myeloid malignancies with either idiopathic disease or underlying germline disorders, including a subset that may be at higher risk for toxicity from treatment.
SECONDARY OBJECTIVES:
I. To describe the preliminary efficacy of post-transplant remission maintenance with decitabine by estimating probabilities of leukemia-free survival (LFS), overall survival (OS), and relapse at 24 months.
II. To assess tolerability of post-transplant remission maintenance with decitabine in combination with filgrastim.
EXPLORATORY OBJECTIVES:
I. To describe the reconstitution of lymphocyte subsets of all enrolled patients.
II. To characterize the biology of relapse in patients receiving post-transplant maintenance:
IIa. By assessing the diversity of the T cell receptor (TCR) repertoire in relapsed and non-relapsed patients;
IIb. By exploring immune escape and MHC-2 expression in relapsed and non-relapse patients;
IIc. By characterizing rare populations of functionally important immune cells in relapsed and non-relapsed patients;
IId. By describing interactions of immune cells and blasts in the bone marrow niche in morphologically relapsed patients.
III. To assess if re-occurrence of post-HCT measurable residual disease (MRD) while on maintenance treatment affects incidence of morphologic relapse by 1 year.
IV. To assess utility of using cell free DNA (circulating cell-free deoxyribonucleic acid [cfDNA]) analysis for monitoring of relapsed disease.
V. Use genetic sequencing (panel sequencing and whole genome/RNA-sequencing to assess genetic changes during treatment with decitabine.
VI. To characterize presence of clonal evolution while receiving decitabine.
OUTLINE:
Patients receive decitabine intravenously (IV) over 60 minutes on days 2-6 of each cycle and filgrastim subcutaneously (SC) on days 1-6 of each cycle as a maintenance therapy post-HCT on study. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and/or biopsy and collection of blood samples throughout the trial. Patients undergo echocardiography (ECHO) during screening and on study and lumbar puncture and brain imaging as clinically indicated.
After completion of study treatment, patients are followed up every 6 months for 2 years post-HCT.
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorFranziska Wachter