Clinical Trials /

Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis

NCT04878003

Description:

This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF) The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.

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

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04878003

Trial Eligibility

Document

Title

  • Brief Title: Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis
  • Official Title: An Open-Label, Multicenter, Phase 2 Study Assessing the Safety and Efficacy of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: KRT-232-114
  • NCT ID: NCT04878003

Conditions

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

Interventions

DrugSynonymsArms
KRT-232Arm 1
TL-895Arm 2

Purpose

This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF) The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalKRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles
  • KRT-232
Arm 2ExperimentalTL-895 administered orally as 150 mg twice daily continuously in 28-day cycles
  • TL-895

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)

          -  High-risk, or intermediate-1 and 2 risk, defined by Dynamic International Prognostic
             System (DIPSS)

          -  ECOG of 0 or 1

        Exclusion Criteria:

          -  Subjects who are positive for p53 mutation (Arm 1)

          -  Prior MDM2 inhibitor therapy or p53-directed therapy (Arm 1)

          -  Prior treatment with any JAK inhibitor

          -  Prior splenectomy

          -  Splenic irradiation within 24 weeks prior to randomization

          -  Prior allogeneic stem-cell transplantation or plans for allogeneic stem-cell
             transplant

          -  History of major organ transplant

          -  Grade 2 or higher QTc prolongation

          -  Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Spleen Volume Reduction (SVR)
Time Frame:24 weeks
Safety Issue:
Description:The proportion of subjects achieving ≥35% SVR at Week 24 by MRI/CT (central review)

Secondary Outcome Measures

Measure:Improvement in Total Symptom Score (TSS)
Time Frame:24 weeks
Safety Issue:
Description:The proportion of subjects who have at least a 50% reduction from Baseline to Week 24 in the total symptom score as measured by the MF-SAF v4.0
Measure:Spleen Response Duration
Time Frame:48 months
Safety Issue:
Description:Time from initial SVR of ≥35% by MRI/CT (central review) until progression
Measure:Rate of conversion from RBC transfusion dependent to independent
Time Frame:24 weeks
Safety Issue:
Description:The proportion of subjects who convert from transfusion dependent to transfusion independent at Week 24
Measure:Overall Survival (OS)
Time Frame:48 months
Safety Issue:
Description:Time from first dose to death from any cause
Measure:Progression free survival (PFS)
Time Frame:48 months
Safety Issue:
Description:Time from randomization to either first occurrence of disease progression or death due to any cause

Details

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

Trial Keywords

  • navtemadlin

Last Updated

August 5, 2021