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

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).