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
Syndax Pharmaceuticals
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.
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 induct…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy 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, rad…
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.
Locations (46)
- UCLA Medical HematologyBurbank, California
- City of Hope Medical CenterDuarte, California
- AdventHealth Blood & Marrow Transplant CenterOrlando, Florida
- Tampa General HospitalTampa, Florida
- Emory Winship Cancer InstituteAtlanta, Georgia
- University of ChicagoChicago, Illinois