KPT-9274 treatment for patients with relapsed or refractory acute myeloid leukemia

A Phase 1 Open-label Study of KPT-9274 in Patients with Relapsed and Refractory Acute Myeloid Leukemia

This study is testing a new oral medication called KPT-9274 to see if it can help patients with relapsed or refractory acute myeloid leukemia who haven't had success with other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Radiation
• Locations: 2 sites (Aurora, Colorado and 1 other locations)
• Trial ID: NCT04914845 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and tolerability of KPT-9274, an oral medication, in patients suffering from relapsed or refractory acute myeloid leukemia (AML). KPT-9274 is a novel small molecule that targets specific pathways involved in AML stem cell metabolism, potentially offering a new therapeutic option for patients who have not responded to previous treatments. The study aims to determine how well this drug can be tolerated and its effectiveness in this challenging patient population. Participants must meet specific eligibility criteria, including having a confirmed diagnosis of AML and limited treatment options.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with relapsed or refractory acute myeloid leukemia who have not responded to prior therapies.

Not a fit: Patients with acute promyelocytic leukemia (APL) or those who have not yet received any prior therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with difficult-to-treat relapsed or refractory AML.

How similar studies have performed: While this approach is novel, previous studies targeting metabolic pathways in AML have shown promise, indicating potential for success.

Eligibility criteria

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 \[hereditary indirect hyperbilirubinemia\], 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).
6. 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
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.

   1. 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.
   2. Women should not breastfeed during treatment with KPT-9724 and for 2 weeks after the last dose.
8. 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 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.

Where this trial is running

Aurora, Colorado and 1 other locations

• UCHealth-Metro Denver — Aurora, Colorado, United States (Recruiting)
• University of Colorado Hospital — Aurora, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Daniel Pollyea, MD — University of Colorado, Denver
• Study coordinator: Derek Schatz

Conditions Acute Myeloid Leukemia; Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory