KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment

Description

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with a JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF. This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT (Arm 2). The BAT administered will be determined by the treating physician, with the option to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any time.

Conditions

Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF)

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Study Overview

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Study Details

Study overview

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with a JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF. This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT (Arm 2). The BAT administered will be determined by the treating physician, with the option to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any time.

A Phase 2/3 Randomized, Controlled, Open-Label Study of KRT 232 in Subjects With Primary Myelofibrosis (PMF), Post Polycythemia Vera MF (Post-PV-MF), Or Post Essential Thrombocythemia MF (Post-ET-MF) Who Are Relapsed or Refractory to Janus Kinase (JAK) Inhibitor Treatment

KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment

Condition
Primary Myelofibrosis (PMF)
Intervention / Treatment

-

Contacts and Locations

Birmingham

The Kirklin Clinic of UAB Hospital, Birmingham, Alabama, United States, 35294

Los Angeles

University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, United States, 90033

Stanford

Stanford Cancer Center - Palo Alto, Stanford, California, United States, 94305

Whittier

Innovative Clinical Research Institute, Whittier, California, United States, 90603

Boynton Beach

University Cancer Institute, Boynton Beach, Florida, United States, 33426

Chicago

Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States, 60611

Chicago

University of Illinois at Chicago, Chicago, Illinois, United States, 60612

Boston

Dana-Farber Cancer Institute, Boston, Massachusetts, United States, 02215

Saint Louis

Washington University School of Medicine, Saint Louis, Missouri, United States, 63110

Brooklyn

Brookdale University Hospital and Medical Center, Brooklyn, New York, United States, 11212

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
  • * High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
  • * Failure of prior treatment with JAK inhibitor
  • * ECOG ≤ 2
  • * Prior splenectomy
  • * Splenic irradiation within 3 months prior to randomization
  • * History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization
  • * History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization
  • * Prior MDM2 inhibitor therapy or p53-directed therapy
  • * Prior allogeneic stem-cell transplant or plans for allogeneic stem cell transplant
  • * History of major organ transplant
  • * Grade 2 or higher QTc prolongation (\> 480 milliseconds per NCI-CTCAE criteria, version 5.0)

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Kartos Therapeutics, Inc.,

Study Record Dates

2025-12-31