KPT-9274 in Patients With Relapsed and Refractory Acute Myeloid Leukemia

Prior treatment

• Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anti-cancer therapy ≤ 2 weeks prior to 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.

Other illness

• Patients with known active central nervous system (CNS) disease
• Clinically significant severe heart disease
• Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment.
• Known, active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen). Testing is not required.
• Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.

Lab values

• White blood cell count ≥25x109/L (hydroxyurea or leukapheresis permitted to reduce to below the exclusion criteria threshold and allow eligibility)

Other

• Female patients who are pregnant or lactating.
• Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea that could interfere with the absorption of KPT-9274.

• Written informed consent obtained prior to any study related procedures required solely for this research study.
• Age ≥18 years.
• Patients with WHO-confirmed non-APL 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.
• Adequate hepatic function:
  • 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).
• Adequate renal function: estimated creatinine clearance of ≥ 60 mL/min, calculated using CKD-EPI Creatinine Equation (2021). https://www.kidney.org/content/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.
• 8\. 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.