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

Acute Myeloid Leukemias Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06226571
• Other study ID #: SNDX-5613-0708
• Status: Recruiting
• Phase: Phase 1
• Start date: May 2024
• Est. completion date: February 2027

Study information

• Verified date: April 2024
• Source: Syndax Pharmaceuticals
• Contact: Syndax Pharmaceuticals
• Phone: 781-419-1400
• Email: clinicaltrials[@]syndax.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Acute Myeloid Leukemias
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• SNDX-5613
Participants will receive SNDX-5613 orally during Induction, Consolidation, and Maintenance until meeting criteria for discontinuation.
• Chemotherapy Regimen
Induction: Participants will receive an intravenous (IV), 2-drug combination of cytarabine and either daunorubicin or idarubicin.
• HiDAC
Consolidation: Participants will receive HiDAC IV.

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
Syndax Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: Number of Participants with Dose-limiting Toxicities		Up to Day 42
Primary	Number of Participants with Treatment-emergent Adverse Events (TEAEs)		Day 1 through 30 days after final dose (up to approximately 3 years)
Secondary	Maximum Plasma Concentration (Cmax) of SNDX-5613 and Relevant Metabolites		Predose through Day 15
Secondary	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
Secondary	Cmax of SNDX-5613 and Relevant Metabolites		Predose through Day 15
Secondary	AUC0-t of SNDX-5613 and Relevant Metabolites		Predose through Day 15