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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 28, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 21, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 21, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 24, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 9, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

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