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An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib

NCT04485260

Description:

This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in combination with ruxolitinib.

Related Conditions:
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT04485260

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib
  • Official Title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib

Clinical Trial IDs

  • ORG STUDY ID: KRT-232-109
  • NCT ID: NCT04485260

Conditions

  • Myelofibrosis

Interventions

DrugSynonymsArms
KRT-232Part A, Arm 1, Cohort 1
RuxolitinibJakafi, JakaviPart A, Arm 1, Cohort 1

Purpose

This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in combination with ruxolitinib.

Trial Arms

NameTypeDescriptionInterventions
Part A, Arm 1, Cohort 1ExperimentalKRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)
  • KRT-232
  • Ruxolitinib
Part A, Arm 2, Cohort 1ExperimentalKRT-232 by mouth once daily for Days 1-5, off treatment for Days 6-28 (28 day cycle)
  • KRT-232
  • Ruxolitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating
             physician according to the World Health Organization (WHO)

          -  Treatment with ruxolitinib for ≥18 weeks prior to study entry, and on a stable dose of
             ruxolitinib in the 8 weeks prior to study entry

          -  Spleen ≥5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT

          -  Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0

          -  ECOG performance status of 0 to 2

        Exclusion Criteria:

          -  Patients who are positive for TP53 mutations

          -  Documented disease progression or clinical deterioration any time while on ruxolitinib
             treatment

          -  Patients who have had a documented spleen response to ruxolitinib.

          -  Prior splenectomy

          -  Prior MDM2 inhibitor therapy or p53-directed therapy
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the KRT-232 RP2D in combination with ruxolitinib
Time Frame:15 months
Safety Issue:
Description:Dose limiting toxicities will be used to establish the MTD of KRT-232 in combination with ruxolitinib. Subsequently, RP2D will be based on safety and efficacy data of the combination.

Secondary Outcome Measures

Measure:To determine spleen response
Time Frame:43 months
Safety Issue:
Description:The proportion of subjects achieving ≥35% SVR at any time point from Baseline while on study, as assessed by MRI (or by CT scan for applicable subjects)
Measure:To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)
Time Frame:43 months
Safety Issue:
Description:The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kartos Therapeutics, Inc.

Last Updated

April 6, 2021