Recruiting
Phase 2
Phase 3

KRT-232 vs. BAT

Sponsor:

Kartos Therapeutics, Inc.

Code:

NCT03662126

Conditions

Primary Myelofibrosis (PMF)

Post-Polycythemia Vera MF (Post-PV-MF)

Post-Essential Thrombocythemia MF (Post-ET-MF)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

KRT-232

Best Available Therapy (BAT)

Study Details

Brief summary:

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)

Study ID

NCT03662126

Start date

Jan 15, 2019

Status verified date

Apr, 2023

Completion date

Dec 31, 2025

Anticipated

Primary completion date

Dec 31, 2023

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion 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

Exclusion Criteria:

  • 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)

Study Design

Enrollment

385 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A Cohort 1

KRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

experimental: Part A Cohort 2

KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

experimental: Part A Cohort 3

KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

experimental: Part A Cohort 4b

KRT-232 240 mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)

experimental: Part B Arm 1 KRT-232

KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

active comparator: Part B Arm 2 Best Available Therapy

Best available therapy at the discretion of the investigator, on a 28-day cycle.

Interventions

KRT-232

KRT-232, administered by mouth

Best Available Therapy (BAT)

Best available therapy options include:

1. hydroxyurea
2. chemotherapy or
3. supportive care (including but not limited to corticosteroids and androgens; JAK inhibitors not allowed).

Primary outcome measure

  • (Part A Only) Spleen Volume Reduction (SVR) [ Time Frame: 24 weeks ]
  • (Part B Only) Spleen Volume Reduction (SVR) [ Time Frame: 24 Weeks ]

Central Contacts and Locations

Central contacts

John Mei

650-542-0136jmei@kartosthera.com

Yulia Khalina

908-656-2799ykhalina@kartosthera.com

Locations

University of Illinois at Chicago

Recruiting

Chicago, Illinois, United States, 60612

Washington University School of Medicine

Recruiting

Saint Louis, Missouri, United States, 63110

Brookdale University Hospital and Medical Center

Recruiting

Brooklyn, New York, United States, 11212

Mt. Sinai

Recruiting

New York, New York, United States, 10029

Gabrail Cancer Center

Recruiting

Canton, Ohio, United States, 44718

Avera Cancer Institute

Recruiting

Sioux Falls, South Dakota, United States, 57105

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37203

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Medical College of Wisconsin - Froedtert Hospital

Recruiting

Milwaukee, Wisconsin, United States, 53226

More Information

Sponsor

Kartos Therapeutics, Inc.

Last update posted

Apr 28, 2023

Last verified

Apr, 2023

Keywords

  • navtemadlin

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Kartos Therapeutics, Inc. on 2023-04-28.