Phase 1 Study of SNDX-5613 in Combination with Intensive Chemotherapy in Participants with AML Harboring Alterations in KMT2A/MLL, NPM1, or NUP98 Genes
- Conditions
- Acute Myeloid Leukemias
- Interventions
- Registration Number
- 2024-514531-18-00
- Lead Sponsor
- Syndax Pharmaceuticals Inc.
- 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.
Recruitment & Eligibility
- Status
- Authorised, recruiting
- Sex
- All
- Target Recruitment
- 22
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 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. 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.
- 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 (12)
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
🇳🇱Rotterdam, Netherlands
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario Marques De Valdecilla
🇪🇸Santander, Spain
Hospital Universitario Y Politecnico La Fe
🇪🇸Valencia, Spain
Hospital Universitario Virgen De Las Nieves
🇪🇸Granada, Spain
Hospital Universitario De Salamanca
🇪🇸Salamanca, Spain
Hospital San Pedro De Alcantara
🇪🇸Caceres, Spain
Scroll for more (2 remaining)Universitair Medisch Centrum Utrecht🇳🇱Utrecht, NetherlandsAnna van RhenenSite contact+31887557655a.vanrhenen@umcutrecht.nl