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.