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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

Sponsor
Kartos Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04485260
Collaborator
(none)
36
Enrollment
38
Locations
1
Arm
44.1
Anticipated Duration (Months)
0.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
36 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 28, 2021
Anticipated Primary Completion Date :
Oct 1, 2022
Anticipated Study Completion Date :
Oct 1, 2024

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib [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.

    2. For Phase 2:To determine the spleen volume reduction (SVR) at Week 24 [6 months after last patient enrolled]

      The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan

    Secondary Outcome Measures

    1. To determine spleen response [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)

    2. To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) [43 months]

      The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Kartos Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kartos Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT04485260
    Other Study ID Numbers:
    • KRT-232-109
    First Posted:
    Jul 24, 2020
    Last Update Posted:
    May 9, 2022
    Last Verified:
    May 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Kartos Therapeutics, Inc.
    navtemadlin
    Additional relevant MeSH terms:
    Polycythemia Vera
    Primary Myelofibrosis
    Polycythemia
    Thrombocytosis
    Thrombocythemia, Essential

    Study Results

    No Results Posted as of May 9, 2022