Status:
ACTIVE_NOT_RECRUITING
KPT-9274 in Patients With Relapsed and Refractory Acute Myeloid Leukemia
Lead Sponsor:
University of Colorado, Denver
Collaborating Sponsors:
Karyopharm Therapeutics Inc
Conditions:
Acute Myeloid Leukemia
Acute Myeloid Leukemia, in Relapse
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This study will evaluate the safety and tolerability of oral KPT-9274 for the treatment of patients with relapsed or refractory acute myeloid leukemia.
Detailed Description
KPT-9274 is a first-in-class orally bioavailable, non-competitive, small molecule, dual modulator of p21 protein (Cdc42/Rac)-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase /PBEF/...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- Female patients who are pregnant or lactating.
- 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.
- White blood cell count ≥25x109/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
- 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.
- 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.
Key Trial Info
Start Date :
August 27 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
February 8 2027
Estimated Enrollment :
40 Patients enrolled
Trial Details
Trial ID
NCT04914845
Start Date
August 27 2021
End Date
February 8 2027
Last Update
September 8 2025
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
University of Colorado Hospital
Aurora, Colorado, United States, 80045