Clinical trial NCT06226571: A Study of SNDX-5613 in Combination With Intensive Chemotherapy in Participants With Acute Myeloid Leukemias
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemias
Keywords: SNDX-5613
Lysine-specific Methyltransferase 2A
KMT2A/MLL
Nucleophosmin 1
NPM1
Nucleoporin 98
NUP98
AML
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-01-26
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Dose Escalation: Number of Participants with Dose-limiting Toxicities
timeFrame: Up to Day 42
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 through 30 days after final dose (up to approximately 3 years)
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of SNDX-5613 and Relevant Metabolites
timeFrame: Predose through Day 15
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 to t (AUC0-t) of SNDX-5613 and Relevant Metabolites
timeFrame: Predose through Day 15
Other outcomes:
Locations:
city: Burbank
country: United States
facility: UCLA Medical Hematology
state: California
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Orlando
country: United States
facility: AdventHealth Blood & Marrow Transplant Center
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University- Center for Hematologic Malignancies
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center (HCC)
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: LDS Hospital - Intermountain Healthcare
state: Utah
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital, Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: Valencia
country: Spain
facility: Universitat de Valencia
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS
Study officials:
References: