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RecruitingInterventionalPhase 1

A Phase 1, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate Safety, Tolerability, and Clinical Activity of SNDX-5613 in Combination With Intensive Chemotherapy in Participants With Newly Diagnosed Acute Myeloid Leukemias Harboring Alterations in Lysine-specific Methyltransferase 2A (KMT2A/MLL), Nucleophosmin 1 (NPM1), and Nucleoporin 98 (NUP98) Genes

NCT ID: NCT06226571Sponsor: Syndax PharmaceuticalsLast updated: 2026-02-17

Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of SNDX-5613 in combination with intensive chemotherapy in participants with newly diagnosed acute myeloid leukemia (AML) harboring alterations in KMT2A, NPM1, or NUP98 genes.

Detailed description

The Dose Escalation portion of this study will identify the maximum tolerated dose, or if different, the recommended Phase 2 dose of SNDX-5613 to be used in combination with intensive chemotherapy and in maintenance monotherapy following intensive chemotherapy in participants with newly diagnosed AML harboring alterations in KMT2A, NPM1, or NUP98 genes. In the Dose Expansion portion of the study, safety and preliminary efficacy of SNDX-5613 may be explored in expansion cohorts at tolerated dose levels. In both Dose Escalation and Dose Expansion, the treatment period will consist of an induction phase (up to 2 cycles), a consolidation phase (up to 4 cycles and could include hematopoietic stem cell transplant for participants who are transplant eligible and have an available donor), and a maintenance monotherapy phase with SNDX-5613. The cycle duration will be 28 days.

Arms & interventions

  • DrugSNDX-5613

    Participants will receive SNDX-5613 orally during Induction, Consolidation, and Maintenance until meeting criteria for discontinuation.

  • DrugChemotherapy Regimen

    Induction: Participants will receive an intravenous (IV), 2-drug combination of cytarabine and either daunorubicin or idarubicin.

  • DrugHiDAC

    Consolidation: Participants will receive HiDAC IV.

Outcome measures

Primary

  • Dose Escalation: Number of Participants with Dose-limiting Toxicities

    Time frame: Up to Day 42

  • Number of Participants with Treatment-emergent Adverse Events (TEAEs)

    Time frame: Day 1 through 30 days after final dose (up to approximately 3 years)

Secondary

  • Maximum Plasma Concentration (Cmax) of SNDX-5613 and Relevant Metabolites

    Time frame: Predose through Day 15

  • Area Under the Plasma Concentration Versus Time Curve From Time 0 to t (AUC0-t) of SNDX-5613 and Relevant Metabolites

    Time frame: Predose through Day 15

Eligibility criteria

Sex: AllAge: 18 Years to 75 YearsHealthy volunteers: No
Inclusion Criteria: * Established, pathologically confirmed diagnosis of AML by World Health Organization 2022 criteria. * Previously untreated AML and eligible to receive intensive chemotherapy. * KMT2Ar, NPM1c, or NUP98r mutations identified by local laboratory prior to the first dose of SNDX-5613. * Eastern Cooperative Oncology Group performance status ≤2 and ≤1 if \>65 years old . * Adequate liver, kidney, and cardiac function. Exclusion Criteria: * Diagnosis of acute promyelocytic leukemia. * Clinically active central nervous system leukemia (blasts detected in cerebrospinal fluid, radiographic or clinical signs and symptoms). * Fridericia's corrected QT interval (QTcF) \>450 milliseconds (average of triplicate), diagnosis or suspicion of Long QT syndrome or family history of Long QT syndrome. * Any gastrointestinal issue of the upper gastrointestinal tract that might affect oral drug absorption or ingestion. * Cirrhosis with a Child-Pugh score of B or C. * Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. * Hepatitis B, Hepatitis C, or HIV-positive with detectable viral load. * Documented active, uncontrolled infection. * Uncontrolled disseminated intravascular coagulation. * Lactating/breast feeding or pregnant. * Use of prohibited concomitant chemotherapy, radiation therapy, or immunotherapy. * Use of strong CYP3A4 inducers or inhibitors (except for Itraconazole, Ketoconazole, Posaconazole, or Voriconazole).

Study locations (26)

UCLA Medical Hematology

Burbank, California, 91505

Recruiting
Gary Schiller, MD · Contact

City of Hope Medical Center

Duarte, California, 91010

Recruiting
Wirlen Elame · Contact
Ibrahim Aldoss, M.D. · Principal Investigator

AdventHealth Blood & Marrow Transplant Center

Orlando, Florida, 32804

Recruiting
Brian Parkin, MD · Contact

Tampa General Hospital

Tampa, Florida, 33606

Recruiting
David Swoboda, MD · Contact

Emory Winship Cancer Institute

Atlanta, Georgia, 30322

Recruiting
William Blum, MD · Contact

University of Chicago

Chicago, Illinois, 60637

Recruiting
Michael Thirman, MD · Contact

University of Louisville Health Brown Cancer Center

Louisville, Kentucky, 40202

Recruiting
Mohamed Hegazi, MD · Contact

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, 40207

Recruiting
Don Stevens, MD · Contact

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Recruiting
Margaret Michaelian · Contact

University of Michigan

Ann Arbor, Michigan, 48109

Recruiting
Dale Bixby, MD · Contact

Allina Health Cancer Institute

Minneapolis, Minnesota, 55407

Recruiting
Fiona He, MD · Contact

Washington University School of Medicine

St Louis, Missouri, 63110

Recruiting
Dr. John DiPersio · Contact

Institution name: Northwell Health-Brany

Lake Success, New York, 11042

Recruiting
David Chitty, MD · Contact

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
Eytan Stein, MD · Contact

University of Rochester Medical Center

Rochester, New York, 14642

Recruiting
Jozal Moore, MD · Contact

SUNY Upstate Medical University

Syracuse, New York, 13210

Recruiting
Teresa Gentile, MD · Contact

East Carolina University

Greenville, North Carolina, 27834

Recruiting
Darla Liles, MD · Contact

Atrium Health Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157

Recruiting
Timoth Pardee, MD · Contact

Cleveland Clinic Foundation

Cleveland, Ohio, 44195

Recruiting
Moaath Mustafa Ali, MD, MPH · Contact

Oregon Health and Science University- Center for Hematologic Malignancies

Portland, Oregon, 97239

Recruiting
Elie Traer, MD · Contact

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Recruiting
Annie lm, MD · Contact

MUSC Hollings Cancer Center (HCC)

Charleston, South Carolina, 29425

Recruiting
Praneeth Baratam, MD · Contact

Baylor University Medical Center

Dallas, Texas, 75246

Recruiting
Bradley Christensen, MD · Contact

The University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Ghayas C. Issa, MD · Contact

LDS Hospital - Intermountain Healthcare

Salt Lake City, Utah, 84143

Recruiting
Bradley Hunter, MD · Contact

West Virginia University

Morgantown, West Virginia, 26506

Recruiting
Carl Shultz, MD · Contact