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

Study Purpose

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.#46;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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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)

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03662126
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2/Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Kartos Therapeutics, Inc.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Australia, Brazil, Bulgaria, Canada, Croatia, Czechia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Lithuania, Mexico, Philippines, Poland, Portugal, Romania, Russian Federation, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF)

Arms & Interventions

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

Drug: - KRT-232

KRT-232, administered by mouth

Drug: - Best Available Therapy (BAT)

Best available therapy options include: hydroxyurea chemotherapy or supportive care (including but not limited to corticosteroids and androgens; JAK inhibitors not allowed).

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

The Kirklin Clinic of UAB Hospital, Birmingham, Alabama

Status

Active, not recruiting

Address

The Kirklin Clinic of UAB Hospital

Birmingham, Alabama, 35294

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