Testing the Addition of an IDH2 Inhibitor, Enasidenib, to Usual Treatment (Cedazuridine-Decitabine) for Higher-Risk Myelodysplastic Syndrome (MDS) With IDH2 Mutation (A MyeloMATCH Treatment Trial)
NCT Number: NCT06577441
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Myelodysplastic Syndrome
Interventions: PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration|PROCEDURE: Bone Marrow Biopsy|DRUG: Decitabine and Cedazuridine|DRUG: Enasidenib
Sponsor: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 54
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-18
Completion Date: 2027-03-01

Summary:
This phase II MyeloMATCH treatment trial compares the usual treatment of cedazuridine-decitabine (ASTX727) to the combination treatment of ASTX727 and enasidenib in treating patients with higher-risk, IDH2-mutated myelodysplastic syndrome (MDS). ASTX727 is a combination of two drugs, decitabine and cedazuridine. 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. Enasidenib is an enzyme inhibitor that may stop the growth of cells by blocking some of the enzymes needed for cell growth. Giving ASTX727 in combination with enasidenib may be effective in treating patients with higher-risk IDH2-mutated MDS.

Primary Outcome Measures: Complete response (CR) rate, Will be assessed using the International Working Group 2023 (IWG2023) criteria. Will compare the CR rate between the two treatment arms to determine if patients treated with enasidenib + ASTX727 have a statistically significantly higher CR rate than patients treated with the ASTX727 monotherapy., Up to 4 cycles of treatment
Secondary Outcome Measures: Event-free survival, Sensitivity analyses will be conducted. Will use the methods of Kaplan-Meier as well as Cox regression models., Time from randomization to either a failure to achieve a CR, CR with limited count recovery (CRL), or CR with partial count recovery (CRh) after four cycles of treatment, relapse, or death due to any cause, assessed up to 18 months|Overall survival, Will use the methods of Kaplan-Meier as well as Cox regression models., Time from randomization to death due to any cause, assessed up to 18 months|Time to response, Will be assessed only among patients who achieve a response (CR, CRL, or CRh)., Time from randomization to documented response, assessed up to 5 years|Duration of response, Will be assessed only among patients who achieve a response (CR, CRL, or CRh). Will use the methods of Kaplan-Meier as well as Cox regression models., From patient first achieves a response until either progression or death, assessed up to 5 years|Incidence of adverse events, Will be determined using the Common Terminology Criteria for Adverse Events version 5 criteria. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest and will graphically assess differences in maximum grades observed for toxicities., Up to 4 weeks after completion of study treatment|Change in IDH2 variant allele frequency (VAF), Will report the percent change of VAF along with a 95% confidence interval., Baseline to end of cycle 4 and 6|Allogeneic stem cell transplantation rate, Will report along with a 95% confidence interval for each treatment arm., Up to 5 years|Measurable residual disease rate, Will be measured by flow cytometry and next generation sequencing (NGS). Will be compared and used to determine association with clinical outcomes such as CR, EFS, or OS., At the end of cycle 4 and 6|Cytogenetic and molecular features, Cytogenetic and molecular classifications including Molecular International Prognostic Scoring System (IPSS-M) will be compared and used to determined association with clinical outcomes such as CR, EFS, and OS., Up to 5 years