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

This is an interventional treatment trial for Acute Myeloid Leukemia Read More

Inclusion Criteria:

1. Written informed consent obtained prior to any study related procedures required solely for this research study.
2. Age ≥18 years.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

5. Adequate hepatic function:

   Total bilirubin < 1.5 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia]; in the case of Gilbert's syndrome the direct bilirubin must be ≤2.0 times the 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).

6. Adequate renal function: estimated creatinine clearance of ≥ 60 mL/min, calculated using the formula of Cockroft and Gault (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.
7. 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.
8. Male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose.

Exclusion Criteria:

1. Female patients who are pregnant or lactating.
2. 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.
3. 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.
4. White blood cell count ≥25x109/L (hydroxyurea or leukapheresis permitted to reduce to below the exclusion criteria threshold and allow eligibility)
5. Patients with known active central nervous system (CNS) disease
6. Clinically significant severe heart disease
7. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment.
8. 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.
9. Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea that could interfere with the absorption of KPT-9274.
10. Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.