KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment
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 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)
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- Kartos Therapeutics, Inc.