Trial | NCT03662126  Report issue

Title

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

  • Phase

    Phase 2

  • Study Type

    Interventional

  • Status

    Recruiting

  • Intervention/Treatment

    navtemadlin ...

  • Study Participants

    385
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.
Study Started
Jan 15
2019
Primary Completion
Dec 31
2023
Anticipated
Study Completion
Dec 31
2025
Anticipated
Last Update
Apr 28
2023

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).

Part A Cohort 1 Experimental

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

Part A Cohort 2 Experimental

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

Part A Cohort 3 Experimental

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

Part A Cohort 4b Experimental

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

Part B Arm 1 KRT-232 Experimental

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

Part B Arm 2 Best Available Therapy Active Comparator

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

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)
No Results Posted