Clinical Trials /

KRT-232 in Subjects With PMF, Post-PV MF, or Post-ET MF Who Have Failed a JAK Inhibitor

NCT03662126

Description:

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 JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF. This study is a global, open-label Phase 2 study to determine the efficacy and safety of KRT-232 in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF who have failed previous treatment with JAK inhibitor (Part A), or Ruxolitinib (Part B). In Part A of the study, patients will be randomly assigned to 2 different doses and 2 different dosing schedules of KRT-232. In Part B of the study, patients will be treated at the recommended dose and schedule from Part A.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Open-label, Phase 2a/2b Study of KRT-232 in Subjects With PMF, Post-PV MF, or Post-ET MF Who Have Failed Ruxolitinib
  • Official Title: An Open-Label, Phase 2a/2b 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 Have Failed Ruxolitinib

Clinical Trial IDs

  • ORG STUDY ID: KRT-232-101
  • NCT ID: NCT03662126

Conditions

  • Primary Myelofibrosis (PMF)
  • Post-Polycythemia Vera MF (Post-PV-MF)
  • Post-Essential Thrombocythemia MF (Post-ET-MF)

Interventions

DrugSynonymsArms
KRT-232Part A Cohort 1

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 ruxolitinib. Inhibition of MDM2 is a novel mechanism of action in MF. This study is a global, open-label Phase 2 study to determine the efficacy and safety of KRT-232 in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF who have failed previous treatment with ruxolitinib. In Part A of the study, patients will be randomly assigned to 2 different doses and 2 different dosing schedules of KRT-232. In Part B of the study, patients will be treated at the recommended dose and schedule from Part A.

Trial Arms

NameTypeDescriptionInterventions
Part A Cohort 1ExperimentalKRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
  • KRT-232
Part A Cohort 2ExperimentalKRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
  • KRT-232
Part A Cohort 3ExperimentalKRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
  • KRT-232
Part BExperimentalRecommended KRT-232 dose and schedule from Part A
  • KRT-232

Eligibility 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 ruxolitinib

          -  ECOG ≤ 2

        Exclusion Criteria:

          -  Prior splenectomy

          -  Splenic irradiation within 3 months prior to the first dose of KRT-232

          -  Active or chronic bleeding within 4 weeks prior to the first dose of KRT-232

          -  Prior MDM2 inhibitor therapy or p53-directed therapy

          -  Prior treatment with HDAC or BCL-2 inhibitors

          -  Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version
             5.0)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine spleen response
Time Frame:24 weeks
Safety Issue:
Description:The proportion of patients achieving a ≥ 35% spleen volume reduction from Baseline to Week 24, as assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scan

Secondary Outcome Measures

Measure:To determine the change in modified MPN-SAF Total Symptom Score (TSS) at Week 24 and Week 48
Time Frame:48 weeks
Safety Issue:
Description:Proportion of patients who have at least a 50% reduction from Baseline to Week 24 and Week 48 in the total symptom score as measured by the modified MPN-SAF v2.0
Measure:RBC transfusion independence at Week 24
Time Frame:24 weeks
Safety Issue:
Description:Proportion of patients who have RBC transfusion independence at week 24
Measure:Complete remission and partial remission defined according to International Working Group-Myeloproliferative Neoplasms Research and Treatment and modified European LeukemiaNet criteria
Time Frame:24 weeks
Safety Issue:
Description:Proportion of patients who have complete remission and partial remission at week 24

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kartos Therapeutics, Inc.

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