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A Study of SNDX-5613 in Combination With Intensive Chemotherapy in Participants With Acute Myeloid Leukemias

NCT06226571 · Syndax Pharmaceuticals
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Official title
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
About this study
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.
Eligibility criteria
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 design
Enrollment target: 76 participants
Allocation: na
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-05-21
Estimated completion: 2027-02
Last updated: 2026-02-17
Interventions
Drug: SNDX-5613Drug: Chemotherapy RegimenDrug: HiDAC
Primary outcomes
  • Dose Escalation: Number of Participants with Dose-limiting Toxicities (Up to Day 42)
  • Number of Participants with Treatment-emergent Adverse Events (TEAEs) (Day 1 through 30 days after final dose (up to approximately 3 years))
Sponsor
Syndax Pharmaceuticals · industry
Contacts & investigators
ContactSyndax Pharmaceuticals · contact · clinicaltrials@syndax.com · 781-419-1400
All locations (46)
UCLA Medical HematologyRecruiting
Burbank, California, United States
City of Hope Medical CenterRecruiting
Duarte, California, United States
AdventHealth Blood & Marrow Transplant CenterRecruiting
Orlando, Florida, United States
Tampa General HospitalRecruiting
Tampa, Florida, United States
Emory Winship Cancer InstituteRecruiting
Atlanta, Georgia, United States
University of ChicagoRecruiting
Chicago, Illinois, United States
University of Louisville Health Brown Cancer CenterRecruiting
Louisville, Kentucky, United States
Norton Cancer Institute, St. Matthews CampusRecruiting
Louisville, Kentucky, United States
Beth Israel Deaconess Medical CenterRecruiting
Boston, Massachusetts, United States
University of MichiganRecruiting
Ann Arbor, Michigan, United States
Allina Health Cancer InstituteRecruiting
Minneapolis, Minnesota, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Institution name: Northwell Health-BranyRecruiting
Lake Success, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
University of Rochester Medical CenterRecruiting
Rochester, New York, United States
SUNY Upstate Medical UniversityRecruiting
Syracuse, New York, United States
East Carolina UniversityRecruiting
Greenville, North Carolina, United States
Atrium Health Wake Forest Baptist Medical CenterRecruiting
Winston-Salem, North Carolina, United States
Cleveland Clinic FoundationRecruiting
Cleveland, Ohio, United States
Oregon Health and Science University- Center for Hematologic MalignanciesRecruiting
Portland, Oregon, United States
UPMC Hillman Cancer CenterRecruiting
Pittsburgh, Pennsylvania, United States
MUSC Hollings Cancer Center (HCC)Recruiting
Charleston, South Carolina, United States
Baylor University Medical CenterRecruiting
Dallas, Texas, United States
The University of Texas, MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
LDS Hospital - Intermountain HealthcareRecruiting
Salt Lake City, Utah, United States
West Virginia UniversityRecruiting
Morgantown, West Virginia, United States
Northern Hospital, VictoriaRecruiting
Epping, Victoria, Australia
Royal Perth HospitalRecruiting
Perth, Western Australia, Australia
Royal Adelaide HospitalRecruiting
Adelaide, Australia
The Alfred Hospital, VictoriaRecruiting
Melbourne, Australia
Sir Charles Gairdner HospitalRecruiting
Nedlands, Australia
University of Alberta HospitalRecruiting
Edmonton, Alberta, Canada
Gordon and Leslie Diamond Health Care CenterRecruiting
Vancouver, British Columbia, Canada
The Sir Mortimer B. Davis Jewish General HospitalRecruiting
Montreal, Quebec, Canada
University Medical Center UtrechtRecruiting
Utrecht, Netherlands
Hospital Universitario Marques de ValdecillaRecruiting
Santander, Cantabria, Spain
Hospital Clinic de BarcelonaRecruiting
Barcelona, Spain
Hospital San Pedro de AlcantaraRecruiting
Cáceres, Spain
Hospital Universitario Virgen de Las NievesRecruiting
Granada, Spain
Hospital General Universitario Gregorio MarañonRecruiting
Madrid, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Hospital Universitario De SalamancaRecruiting
Salamanca, Spain
Hospital Universitario Virgen del Rocio - PPDSRecruiting
Seville, Spain
Universitat de ValenciaRecruiting
Valencia, Spain
Hammersmith HospitalRecruiting
London, London, City of, United Kingdom
The Royal Marsden NHSRecruiting
Sutton, United Kingdom
A Study of SNDX-5613 in Combination With Intensive Chemotherapy in Participants With Acute Myeloid Leukemias · TrialPath