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

May 5, 2022 updated by: Kartos Therapeutics, Inc.
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia
        • Recruiting
        • Royal Adelaide Hospital
  • Bulgaria
      • Pleven, Bulgaria
        • Recruiting
        • Dr. Georgi Stranski
      • Sofia, Bulgaria, 1431
        • Recruiting
        • Saint Ivan Rilski Hospital
      • Sofia, Bulgaria, 1431
        • Recruiting
        • University Mutiprofile Hospital Alexandrovska
  • France
      • Angers, France, 49933
        • Recruiting
        • CHU Angers
      • Le Mans, France, 72000
        • Recruiting
        • Centre Hospitalier du Mans
      • Marseille, France, 13009
        • Recruiting
        • Institut Paoli-Calmettes
      • Montpellier, France, 34295
        • Recruiting
        • Chu Saint Eloi
      • Paris, France
        • Recruiting
        • Hopital Saint Louis
      • Tours, France
        • Recruiting
        • CHU Tours - Hôpital Bretonneau
    • Cedex 9
      • Caen, Cedex 9, France, 14033
        • Recruiting
        • CHU de Caen
  • Germany
      • Aachen, Germany, 52074
        • Recruiting
        • Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
      • Halle, Germany, 6120
        • Recruiting
        • Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/Onkologie
      • Jena, Germany
        • Recruiting
        • Universitaetsklinikum Jena
      • Mainz, Germany, 55131
        • Recruiting
        • UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und Poliklinik
      • Mutlangen, Germany, 73557
        • Recruiting
        • Stauferklinikum Schwäbisch Gmünd
  • Israel
      • Zerifin, Israel, 7033001
        • Recruiting
        • Shamir Medical Center ( Assaf Harofeh)
  • Italy
      • Bologna, Italy, 340136
        • Recruiting
        • Bologna University Hospital, Institute of Hematology
      • Catania, Italy, 95124
        • Recruiting
        • Universita degli Studi di Catania
      • Firenze, Italy, 50134
        • Recruiting
        • University of Florence
      • Meldola, Italy, 47014
        • Recruiting
        • Istituto Tumori della Romagna (IRST)
      • Varese, Italy, 21100
        • Recruiting
        • Ospedale di Circolo e Fondazione MacchiASST Sette Laghi
  • Poland
      • Kraków, Poland
        • Recruiting
        • Oddział Kliniczny Hematologii Szpitala Uniwersyteckiego w Krakowie
      • Opole, Poland
        • Recruiting
        • Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny Hematologii
  • Spain
      • Barcelona, Spain, 08916
        • Recruiting
        • Hospital Universitario Germans Trias i Pujol
      • Barcelona, Spain, 08035
        • Recruiting
        • d'Hebron University Hospital in Barcelona
      • Las Palmas De Gran Canaria, Spain
        • Recruiting
        • Hospital Universitario de Gran Canaria Doctor Negrin
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Virgen de la Victoria
      • Salamanca, Spain
        • Recruiting
        • Hospital Universitario de Salamanca
      • Zaragoza, Spain, 50012
        • Recruiting
        • Hospital de Dia Quiron Zaragoza
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City Of Hope
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • John Hopkins University
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School Of Medicine At Mount Sinai
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Cleveland Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A, Arm 1, Cohort 1
KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)
Drug: KRT-232
administered by mouth
Drug: Ruxolitinib
administered by mouth
Other Names:
  • Jakafi
  • Jakavi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib
Time Frame: 15 months
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.
15 months
For Phase 2:To determine the spleen volume reduction (SVR) at Week 24
Time Frame: 6 months after last patient enrolled
The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan
6 months after last patient enrolled

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine spleen response
Time Frame: 43 months
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)
43 months
To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)
Time Frame: 43 months
The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study
43 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kartos Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2021

Primary Completion (Anticipated)

October 1, 2022

Study Completion (Anticipated)

October 1, 2024

Study Registration Dates

First Submitted

July 21, 2020

First Submitted That Met QC Criteria

July 21, 2020

First Posted (Actual)

July 24, 2020

Study Record Updates

Last Update Posted (Actual)

May 9, 2022

Last Update Submitted That Met QC Criteria

May 5, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KRT-232-109

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelofibrosis

Clinical Trials on KRT-232

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Costa Rica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe