KPT-9274 for the Treatment of Recurrent and Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Written informed consent obtained prior to any screening procedures
• Age >= 18 years
• Patients with World Health Organization (WHO)-confirmed non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML) who have not responded to or relapsed after at least one prior therapy and for whom no standard therapy that may provide clinical benefit is available.
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Total bilirubin < 1.5 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome [hereditary indirect hyperbilirubinemia], subjects with Gilbert’s syndrome, total bilirubin needs to be ≤ 4 x ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times ULN (except patients with known liver involvement of their AML who must have AST and ALT =< 5.0 times ULN).
• Estimated creatinine clearance of >= 60 mL/min, calculated using Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation (2021)
• Female patients of child-bearing potential must agree to use dual methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at screening. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose * Fertile female patients must agree to refrain from egg donation from first dose until at least 3 months following the last dose of KPT-9724 * Women should not breastfeed during treatment with KPT-9724 and for 2 weeks after the last dose
• Male patients must use 2 highly effective methods of contraception if sexually active with a female of child-bearing potential, during treatment with KPT-9724, during a period of 2 weeks (5 half-lives) after the last dose of KPT-9724 plus a period of 3 months. (for 3.5 months after their last dose of KPT-9724). Fertile male patients must agree to refrain from sperm donation from first dose until at least 3.5 months following the last dose of KPT-9724

Exclusion Criteria

• Female patients who are pregnant or lactating
• Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anti-cancer therapy =< 2 weeks prior to cycle 1 day 1 (C1D1). Hydroxyurea is not considered an anti-cancer therapy.
• Patients who have not recovered or stabilized (grade 1 or to their baseline for non-hematologic toxicities) from toxicities related to their previous treatment, except for alopecia.
• White blood cell count >= 25 x 10^9/L (hydroxyurea or leukapheresis permitted to reduce to below the exclusion criteria threshold and allow eligibility)
• Patients with known active central nervous system (CNS) disease
• Clinically significant severe heart disease
• Active clinically significant infection. Use of prophylactic antibiotics, antivirals or antifungals are permitted.
• Known, active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) ribonucleic acid (RNA) or hepatitis B virus surface antigen (HBsAg). Testing is not required.
• Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea that could interfere with the absorption of KPT-9274.
• Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.