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Phase II/III KRT-232 in PMF, Post-PV-MF or Post-ET-MF who're Relapsed/Refractory to JAK Inhibitor Tx
Not Recruiting
Trial ID: NCT03662126
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.
Official Title
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
Stanford Investigator(s)
Jason R Gotlib
Professor of Medicine (Hematology)
Eligibility
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)
Intervention(s):
drug: KRT-232
drug: Best Available Therapy (BAT)
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
Justin Abuel
6507231367