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

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemias
• Interventions: Drug: SNDX-5613; Drug: Chemotherapy Regimen; Drug: HiDAC

• Registration Number: NCT06226571
• Lead Sponsor: Syndax Pharmaceuticals

Brief 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.

Study Timeline

• Study First Submitted: 2024-01-12
• Study First Submitted QC: 2024-01-23
• Study First Posted: 2024-01-26
• Study Start: 2024-05-21
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-10
• Primary Completion: 2027-02
• Study Completion: 2027-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 76

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.

Read More

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).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
SNDX-5613	SNDX-5613	Dose Escalation: * Induction: Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen. * Consolidation: Cohorts will receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613. * Maintenance Monotherapy: Cohorts will receive SNDX-5613. Dose Expansion: * Induction: SNDX-5613 at tolerated dose level with chemotherapy regimen. * Consolidation: Cohorts will receive SNDX-5613 with chemotherapy regimen and HiDAC. * Maintenance Monotherapy: Cohorts will receive SNDX-5613.
SNDX-5613	Chemotherapy Regimen	Dose Escalation: * Induction: Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen. * Consolidation: Cohorts will receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613. * Maintenance Monotherapy: Cohorts will receive SNDX-5613. Dose Expansion: * Induction: SNDX-5613 at tolerated dose level with chemotherapy regimen. * Consolidation: Cohorts will receive SNDX-5613 with chemotherapy regimen and HiDAC. * Maintenance Monotherapy: Cohorts will receive SNDX-5613.
SNDX-5613	HiDAC	Dose Escalation: * Induction: Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen. * Consolidation: Cohorts will receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613. * Maintenance Monotherapy: Cohorts will receive SNDX-5613. Dose Expansion: * Induction: SNDX-5613 at tolerated dose level with chemotherapy regimen. * Consolidation: Cohorts will receive SNDX-5613 with chemotherapy regimen and HiDAC. * Maintenance Monotherapy: Cohorts will receive SNDX-5613.

Primary Outcome Measures

Name	Time	Method
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)

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration Versus Time Curve From Time 0 to t (AUC0-t) of SNDX-5613 and Relevant Metabolites	Predose through Day 15
Maximum Plasma Concentration (Cmax) of SNDX-5613 and Relevant Metabolites	Predose through Day 15

Trial Locations

Locations (14)

UCLA Medical Hematology; 🇺🇸 Burbank, California, United States

City of Hope Medical Center; 🇺🇸 Duarte, California, United States

AdventHealth Blood & Marrow Transplant Center; 🇺🇸 Orlando, Florida, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

Emory Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Norton Cancer Institute, St. Matthews Campus; 🇺🇸 Louisville, Kentucky, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

SUNY Upstate Medical University; 🇺🇸 Syracuse, New York, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

MUSC Hollings Cancer Center (HCC); 🇺🇸 Charleston, South Carolina, United States

The University of Texas, MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

LDS Hospital - Intermountain Healthcare; 🇺🇸 Salt Lake City, Utah, United States

West Virginia University; 🇺🇸 Morgantown, Virginia, United States