RECRUITING

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)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Randomized Phase II Trial of Enasidenib-Based Therapies Versus Cedazuridine-Decitabine in Higher-Risk IDH2-Mutated Myelodysplastic Syndrome: A MyeloMATCH Treatment Trial

Quick Facts

Study Start:2025-12-27

Study Completion:2027-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06577441

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* GENERAL MYLEOMATCH MSRP REGISTRATION CRITERIA: * Patients must be registered to the Master Screening and Reassessment Protocol (MSRP) and assigned to this protocol by the MATCHBox Treatment Verification Team. * Participants must not have received prior anti-cancer therapy for AML or MDS. * Note: Hydroxyurea to control the white blood cell count (WBC) is allowed. * Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility. * Participants must not be currently receiving any cytarabine-containing therapy other than up to 1 g/m\^2 of cytarabine, which is allowed for urgent cytoreduction. The use of prior hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide is allowed. * REGISTRATION ELIGIBILITY CRITERIA (STEP 1) * Patients must have a morphologically-confirmed diagnosis of MDS with a Revised International Prognostic Scoring System (IPSS-R) score ≥ 4. * Patients must have a detectable pathogenic IDH2 mutation based on the National Cancer Institute (NCI) Myeloid Panel. * No prior treatment with deoxyribonucleic acid (DNA) methyltransferase inhibitors (ASTX727, azacitidine, or decitabine). * Prior treatment with growth factors (ESA, granulocyte colony-stimulating factor \[g-CSF\], TPO agonist), lenalidomide or luspatercept is allowed with a maximum limit of 1 month of exposure. * Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Total bilirubin ≤ 2.0 x upper limit of normal (ULN) * Unless elevated due to Gilbert's syndrome. In patients with Gilbert's syndrome if direct bilirubin is within normal limits, then they are eligible for enrollment. * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\[) ≤ 3.0 x upper limit of normal (ULN) * Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73m\^2 * Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects. * Therefore, for women of childbearing potential only, a negative pregnancy test done as part of screening lab work prior to registration is required. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2) * Patients on the ASTX727 monotherapy arm (Arm A) that do not achieve a CR (complete response), CRL (CR with limited count recovery), or CRh (CR with partial count recovery) after completing 6 cycles of study treatment. * ECOG performance status ≤ 2 * Total bilirubin ≤ 2.0 x upper limit of normal (ULN). * Unless elevated due to Gilbert's syndrome. In patients with Gilbert's syndrome if direct bilirubin is within normal limits, then they are eligible for enrollment. * AST (SGOT)/ALT (SGPT) ≤ 3.0 x upper limit of normal (ULN) * GFR ≥ 30 mL/min/1.73m\^2 * Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* GENERAL MYLEOMATCH MSRP REGISTRATION CRITERIA:
* Patients must be registered to the Master Screening and Reassessment Protocol (MSRP) and assigned to this protocol by the MATCHBox Treatment Verification Team.
* Participants must not have received prior anti-cancer therapy for AML or MDS.
* Note: Hydroxyurea to control the white blood cell count (WBC) is allowed.
* Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility.
* Participants must not be currently receiving any cytarabine-containing therapy other than up to 1 g/m\^2 of cytarabine, which is allowed for urgent cytoreduction. The use of prior hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide is allowed.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1)
* Patients must have a morphologically-confirmed diagnosis of MDS with a Revised International Prognostic Scoring System (IPSS-R) score ≥ 4.
* Patients must have a detectable pathogenic IDH2 mutation based on the National Cancer Institute (NCI) Myeloid Panel.
* No prior treatment with deoxyribonucleic acid (DNA) methyltransferase inhibitors (ASTX727, azacitidine, or decitabine).
* Prior treatment with growth factors (ESA, granulocyte colony-stimulating factor \[g-CSF\], TPO agonist), lenalidomide or luspatercept is allowed with a maximum limit of 1 month of exposure.
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Total bilirubin ≤ 2.0 x upper limit of normal (ULN)
* Unless elevated due to Gilbert's syndrome. In patients with Gilbert's syndrome if direct bilirubin is within normal limits, then they are eligible for enrollment.
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\[) ≤ 3.0 x upper limit of normal (ULN)
* Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73m\^2
* Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects.
* Therefore, for women of childbearing potential only, a negative pregnancy test done as part of screening lab work prior to registration is required.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2)
* Patients on the ASTX727 monotherapy arm (Arm A) that do not achieve a CR (complete response), CRL (CR with limited count recovery), or CRh (CR with partial count recovery) after completing 6 cycles of study treatment.
* ECOG performance status ≤ 2
* Total bilirubin ≤ 2.0 x upper limit of normal (ULN).
* Unless elevated due to Gilbert's syndrome. In patients with Gilbert's syndrome if direct bilirubin is within normal limits, then they are eligible for enrollment.
* AST (SGOT)/ALT (SGPT) ≤ 3.0 x upper limit of normal (ULN)
* GFR ≥ 30 mL/min/1.73m\^2
* Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Anand A Patel

PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Study Locations (Sites)

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, 48114

United States

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, 48188

United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, 48118

United States

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, 48154

United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, 48197

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Anand A Patel, PRINCIPAL_INVESTIGATOR, Alliance for Clinical Trials in Oncology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-12-27

Study Completion Date2027-03-01

Study Record Updates

Study Start Date2025-12-27

Study Completion Date2027-03-01

Terms related to this study

Additional Relevant MeSH Terms

Myelodysplastic Syndrome