A Phase 2 Clinical Study of Ziftomenib in Patients With Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia

Inclusion Criteria:

* Voluntary written informed consent and willingness to comply with all study procedures
* Age ≥ 18 years
* Confirmed diagnosis of acute myeloid leukemia (AML)
* Patients with R/R AML with NPM1-m
* No available standard of care expected to provide clinical benefit, ineligible for or declined standard therapy.
* ECOG performance status 0-2.
* White blood cell count ≤ 30,000/mm³ at screening (hydroxyurea permitted for cytoreduction).
* Adequate organ function according to protocol requirements.
* Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment.
* Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment.

Exclusion Criteria:

* Diagnosis of acute promyelocytic leukemia.
* Donor lymphocyte infusion \< 30 days prior to study entry.
* Clinically active central nervous system (CNS) leukemia.
* Prior hematopoietic stem cell transplantation (HSCT) without adequate hematologic recovery.
* Active Grade ≥ 2 acute graft-versus-host disease or moderate/severe chronic graft-versus-host disease.
* Prior treatment with a menin inhibitor.
* Receipt of chemotherapy, immunotherapy, radiotherapy, or investigational therapy within 14 days or 5 half-lives prior to first dose.
* Unresolved toxicities from prior therapy \> Grade 1.
* Requirement for strong CYP3A4 inducers.
* Active or uncontrolled infection, including hepatitis B, hepatitis C, or HIV.
* Conditions predisposing to serious or life-threatening infection or significant immunodeficiency.
* Cardiovascular disease or QTcF \> 480 ms.
* Interstitial lung disease.
* Major surgery within 4 weeks prior to first dose.
* Women who are pregnant or lactating
* Any medical, psychiatric, or social condition that may interfere with study participation or safety, or that makes the patient unsuitable in the investigator's judgment.