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
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
Study locations (26)
UCLA Medical Hematology
Burbank, California, 91505
City of Hope Medical Center
Duarte, California, 91010
AdventHealth Blood & Marrow Transplant Center
Orlando, Florida, 32804
Tampa General Hospital
Tampa, Florida, 33606
Emory Winship Cancer Institute
Atlanta, Georgia, 30322
University of Chicago
Chicago, Illinois, 60637
University of Louisville Health Brown Cancer Center
Louisville, Kentucky, 40202
Norton Cancer Institute, St. Matthews Campus
Louisville, Kentucky, 40207
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of Michigan
Ann Arbor, Michigan, 48109
Allina Health Cancer Institute
Minneapolis, Minnesota, 55407
Washington University School of Medicine
St Louis, Missouri, 63110
Institution name: Northwell Health-Brany
Lake Success, New York, 11042
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Rochester Medical Center
Rochester, New York, 14642
SUNY Upstate Medical University
Syracuse, New York, 13210
East Carolina University
Greenville, North Carolina, 27834
Atrium Health Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Oregon Health and Science University- Center for Hematologic Malignancies
Portland, Oregon, 97239
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
MUSC Hollings Cancer Center (HCC)
Charleston, South Carolina, 29425
Baylor University Medical Center
Dallas, Texas, 75246
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
LDS Hospital - Intermountain Healthcare
Salt Lake City, Utah, 84143
West Virginia University
Morgantown, West Virginia, 26506