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KRT-232 in Subjects With PMF, Post-PV MF, or Post-ET MF Who Have Failed a JAK Inhibitor

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ClinicalTrials.gov Identifier: NCT03662126
Recruitment Status : Recruiting
First Posted : September 7, 2018
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

Brief Summary:

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF.

This study is a global, open-label Phase 2 study to determine the efficacy and safety of KRT-232 in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF who have failed previous treatment with JAK inhibitor (Part A), or Ruxolitinib (Part B). In Part A of the study, patients will be randomly assigned to 2 different doses and 2 different dosing schedules of KRT-232. In Part B of the study, patients will be treated at the recommended dose and schedule from Part A.


Condition or disease Intervention/treatment Phase
Primary Myelofibrosis (PMF) Post-Polycythemia Vera MF (Post-PV-MF) Post-Essential Thrombocythemia MF (Post-ET-MF) Drug: KRT-232 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 247 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 2a/2b Study of KRT-232 in Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post-ET-MF) Who Have Failed a JAK Inhibitor
Actual Study Start Date : January 15, 2019
Estimated Primary Completion Date : August 1, 2021
Estimated Study Completion Date : February 28, 2023


Arm Intervention/treatment
Experimental: Part A Cohort 1
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Drug: KRT-232
KRT-232, administered by mouth

Experimental: Part A Cohort 2
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Drug: KRT-232
KRT-232, administered by mouth

Experimental: Part A Cohort 3
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Drug: KRT-232
KRT-232, administered by mouth

Experimental: Part B
Recommended KRT-232 dose and schedule from Part A
Drug: KRT-232
KRT-232, administered by mouth

Experimental: Part A Cohort 4
KRT-232 360mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Drug: KRT-232
KRT-232, administered by mouth

Experimental: Part A Cohort 5
KRT-232 180mg by mouth once daily for Days 1-7, off treatment for Days 8-14, on treatment for Days 15-21, off treatment for Days 22-28 (28-day cycles)
Drug: KRT-232
KRT-232, administered by mouth

Experimental: Part A Cohort 6
KRT-232 120mg by mouth once daily for Days 1-14, off treatment for Days 15-21 (21-day cycles)
Drug: KRT-232
KRT-232, administered by mouth

Experimental: Part A Cohort 7
KRT-232 60mg by mouth once daily for Days 1-21, off treatment for Days 22-28 (28-day cycles)
Drug: KRT-232
KRT-232, administered by mouth




Primary Outcome Measures :
  1. To determine spleen response [ Time Frame: 24 weeks ]
    The proportion of patients achieving a ≥ 35% spleen volume reduction from Baseline to Week 24, as assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scan


Secondary Outcome Measures :
  1. To determine the change in modified MPN-SAF Total Symptom Score (TSS) at Week 24 and Week 48 [ Time Frame: 48 weeks ]
    Proportion of patients who have at least a 50% reduction from Baseline to Week 24 and Week 48 in the total symptom score as measured by the modified MPN-SAF v2.0

  2. RBC transfusion independence at Week 24 [ Time Frame: 24 weeks ]
    Proportion of patients who have RBC transfusion independence at week 24

  3. Complete remission and partial remission defined according to International Working Group-Myeloproliferative Neoplasms Research and Treatment and modified European LeukemiaNet criteria [ Time Frame: 24 weeks ]
    Proportion of patients who have complete remission and partial remission at week 24



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
  • High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
  • Failure of prior treatment with JAK inhibitor (Part A) or ruxolitinib (Part B)
  • ECOG ≤ 2

Exclusion Criteria:

  • Prior splenectomy
  • Splenic irradiation within 3 months prior to the first dose of KRT-232
  • Active or chronic bleeding within 4 weeks prior to the first dose of KRT-232
  • Prior MDM2 inhibitor therapy or p53-directed therapy
  • Prior treatment with HDAC or BCL-2 inhibitors
  • Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03662126


Contacts
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Contact: John Mei 650-542-0136 jmei@kartosthera.com

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Locations
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United States, Alabama
The Kirklin Clinic of UAB Hospital Recruiting
Birmingham, Alabama, United States, 35294
United States, California
University of California San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
University of Southern California Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Stanford Cancer Center - Palo Alto Recruiting
Stanford, California, United States, 94305
Innovative Clinical Research Institute Recruiting
Whittier, California, United States, 90603
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06519
United States, Florida
University Cancer Institute Recruiting
Boynton Beach, Florida, United States, 33426
United States, Illinois
Northwestern University Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
Health Partners Institute Recruiting
Saint Paul, Minnesota, United States, 55101
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Summit Medical Group Recruiting
Florham Park, New Jersey, United States, 07932
Contact    973-538-5210      
United States, New York
Brookdale University Hospital and Medical Center Recruiting
Brooklyn, New York, United States, 11212
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
The Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Canada, Alberta
Tom Baker Cancer Center Recruiting
Calgary, Alberta, Canada, T2N4N2
Canada, Ontario
Princess Margaret Cancer Center Recruiting
Toronto, Ontario, Canada, M5G 2M9
Czechia
Fakultní Nemocnice Olomouc Recruiting
Olomouc, Czechia, 779 00
Fakultní Nemocnice Olomouc Recruiting
Olomouc, Czechia, 77900
Fakultní Nemocnice Královské Vinohrady Recruiting
Prague, Czechia, 10034
France
Center Hospitalier Universitaire d'Angers Recruiting
Angers, France, 49933 Cedex 09
Institut Bergonié Recruiting
Bordeaux, France, 33076
Centre Hospitalier Regional Universitaire Brest Hopital Morvan Recruiting
Brest Cedex, France, 29609
Centre Hospitalier Universitaire of Caen Normandie - Côte de Nacre Recruiting
Caen, France, 14000
Hôpital Claude Huriez Recruiting
Lille, France, 59037
Centre Hospitalier Universitaire de Nîmes Recruiting
Nîmes, France, 30029 Cedex 9
Hôpital Saint-Louis Recruiting
Paris, France, 75010
Institut Universitaire du Cancer de Toulouse Oncopole Recruiting
Toulouse, France, 31059
Germany
Universitätsmedizin Mannheim Recruiting
Mannheim, Baden-Wuerttemberg, Germany, 68167
Klinikum Rechts der Isar der Technischen Universität München Apotheke Recruiting
München, Bayern, Germany, 81675
Universitätsklinikum Aachen Recruiting
Aachen, Nordrhein-Westfalen, Germany, 52074
Universitaetsklinikum Essen Recruiting
Essen, Nordrhein-Westfalen, Germany, 45147
Universitätsklinikum Halle Recruiting
Halle, Sachsen-Anhalt, Germany, 06120
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle Recruiting
Dresden, Sachsen, Germany, 01307
Technische Universität Dresden Recruiting
Dresden, Sachsen, Germany, 01307
Universitätsklinikum Jena Recruiting
Jena, Thuringen, Germany, 07747
Charité Universitätsmedizin Berlin Recruiting
Berlin, Germany, 13353
Stauferklinikum Schwäbisch Gmünd Recruiting
Mutlangen, Germany, 73557
Hungary
Somogy Megyei Kaposi Mór Oktató Kórház Recruiting
Kaposvár, Somogy, Hungary, 7400
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház Recruiting
Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary, 4400
Semmelweis Egyetem Recruiting
Budapest, Hungary, 1083
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet Recruiting
Budapest, Hungary
Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum Recruiting
Debrecen, Hungary, 4032
Szegedi Tudományegyetem Recruiting
Szeged, Hungary, 6725
Poland
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku Recruiting
Wrocław, Dolnoslaskie, Poland, 53-439
Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza Recruiting
Brzozow, Podkarpackie, Poland, 36-200
Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich Recruiting
Chorzów, Slaskie, Poland, 41-500
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie Recruiting
Lublin, Poland, 20-081
Szpital Wojewódzki w Opolu Recruiting
Opole, Poland, 45-061
Clinical Research Center Spółka z Ograniczoną Odpowiedzialnością Medic-R sp. k. Recruiting
Poznań, Poland, 60-848
Spain
Hospital Universitari Germans Trias i Pujol Recruiting
Badalona, Barcelona, Spain, 08916
Hospital Universitario de Gran Canaria Doctor Negrin Recruiting
Las Palmas De Gran Canaria, Las Palmas, Spain, 35010
Hospital Universitario Puerta de Hierro - Majadahonda Recruiting
Majadahonda, Madrid, Spain, 28222
Hospital Universitario Ramón Y Cajal Recruiting
Madrid, Spain, 28034
Hospital Universitario Virgen de la Victoria Recruiting
Málaga, Spain, 29010
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Juan Carlos Hernandez Boluda    34963493605      
United Kingdom
University Hospitals Birmingham NHS Foundation Trust Recruiting
Birmingham, United Kingdom
NHS Greater Glasgow and Clyde Recruiting
Glasgow, United Kingdom
Guy's and Saint Thomas' NHS Foundation Trust Recruiting
London, United Kingdom, SE1 9RT
Oxford University Hospitals NHS Foundation Trust Recruiting
Oxford, United Kingdom
Sponsors and Collaborators
Kartos Therapeutics, Inc.

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Responsible Party: Kartos Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03662126     History of Changes
Other Study ID Numbers: KRT-232-101
First Posted: September 7, 2018    Key Record Dates
Last Update Posted: July 30, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Molecular Mechanisms of Pharmacological Action