KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment (BOREAS)

A Phase 2/3 Randomized, Controlled, Open-Label 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 Are Relapsed or Refractory to Janus Kinase (JAK) Inhibitor Treatment

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 a JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF.

This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT (Arm 2). The BAT administered will be determined by the treating physician, with the option to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any time.

Study Overview

• Status: Recruiting
• Conditions: Primary Myelofibrosis (PMF); Post-Polycythemia Vera MF (Post-PV-MF); Post-Essential Thrombocythemia MF (Post-ET-MF)
• Intervention / Treatment: Drug: KRT-232; Drug: Best Available Therapy (BAT)

• Study Type: Interventional
• Enrollment (Anticipated): 385
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Yulia Khalina; Phone Number: 908-656-2799; Email: ykhalina@kartosthera.com

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Recruiting
    • Instituto Medico Alexander Fleming
  • Caba, Argentina, 1425
    • Recruiting
    • Centro Medico San Luis
  • Córdoba, Argentina, X5016KEH
    • Recruiting
    • Hospital Privado - Centro Medico de Cordoba - Oncology
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000ORE
      • Recruiting
      • Sanatorio de la Mujer
• Australia
  • Adelaide, Australia
    • Recruiting
    • Royal Adelaide Hospital
  • Melbourne, Australia
    • Recruiting
    • The Alfred Hospital
  • Noble Park, Australia, 3174
    • Recruiting
    • South Eastern Private Hospital
  • South Brisbane, Australia
    • Recruiting
    • Icon Cancer Center
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Recruiting
      • Fiona Stanley Hosital
• Brazil
  • Goiânia, Brazil, 74605
    • Recruiting
    • Hospital das Clínicas UFG
  • Jau, Brazil, 17210-120
    • Recruiting
    • Fundação Doutor Amaral Carvalho
  • Porto Alegre, Brazil, 90035-903
    • Recruiting
    • Hospital de Clinicas de Porto Alegre - Centro de Pesquisa Clinica
  • Porto Alegre, Brazil, 90880-480
    • Recruiting
    • Associação Educadora São Carlos AESC - Hospital Mãe de Deus - Centro de Pesquisa
  • Sao Paulo, Brazil, 01236-030
    • Recruiting
    • Instituto de Ensino E Pesquisa Sao Lucas
  • Sao Paulo, Brazil, 05403-000
    • Recruiting
    • Hospital das Clínicas da Universidade de São Paulo
  • Sao Paulo, Brazil, 01509-900
    • Recruiting
    • Hospital A C Camargo - Fundacao Antonio Prudente
  • São Paulo, Brazil, 04502-001
    • Recruiting
    • Instituto D'Or de Pesquisa e Ensino
  • São Paulo, Brazil, 1321001
    • Recruiting
    • Instituto COI São Paulo
  • Ceara
    • Fortaleza, Ceara, Brazil, 60140-025
      • Recruiting
      • Centro de oncologia Leonardo da Vinci
  • Parana
    • Curitiba, Parana, Brazil, 81520
      • Recruiting
      • Hospital Erasto Gaertner
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083
      • Recruiting
      • UNICAMP - Universidade Estadual de Campinas Hemocentro
• Bulgaria
  • Pleven, Bulgaria
    • Recruiting
    • University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven
  • Plovdiv, Bulgaria
    • Recruiting
    • University Multiprofile Hospital for Active Treatment Sveti Georgi, Plovdiv
  • Sofia, Bulgaria
    • Recruiting
    • Acibadem City Clinic Tokuda Hospital, Sofia
  • Sofia, Bulgaria
    • Recruiting
    • Specialized Hospital for Active Therapy of Hematological Disorders
  • Sofia, Bulgaria
    • Recruiting
    • University Multiprofile Hospital for Active Treatment Saint Ivan Rilski, Sofia
  • Sofia, Bulgaria
    • Withdrawn
    • University Multiprofile Hospital for Active Treatment Alexandrovska, Sofia
  • Sofia, Bulgaria, 1606
    • Recruiting
    • Military Medical Academy, Multiprofile for active treatment, Sofia
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Active, not recruiting
      • Princess Margaret Cancer Center
• Croatia
  • Sibenik, Croatia, 22000
    • Recruiting
    • General Hospital Sibenik
  • Zagreb, Croatia, 10000
    • Recruiting
    • Clinical Hospital Centre Osijek
  • Zagreb, Croatia, 10000
    • Recruiting
    • KB Sestre Milosrdnice
• Czechia
  • Králová, Czechia, 500 05
    • Recruiting
    • FN Hradec Kralove
  • Nové Město, Czechia
    • Recruiting
    • Vseonecma fakultni nemocrince V Praze
  • Olomouc, Czechia, 779 00
    • Withdrawn
    • Fakultní Nemocnice Olomouc
• France
  • Amiens, France, 80054
    • Recruiting
    • Centre Hospitalier Universitaire D'Amiens (Hopital Sud) - Hématologie Clinique
  • Angers, France, 49933 Cedex 09
    • Recruiting
    • Center Hospitalier Universitaire d'Angers
  • Bayonne, France, 64100
    • Recruiting
    • C.H de la Côte Basque - Serviv
  • Brest Cedex, France, 29609
    • Recruiting
    • Centre Hospitalier Regional Universitaire Brest Hopital Morvan
  • Caen, France, 14000
    • Active, not recruiting
    • Centre Hospitalier Universitaire of Caen Normandie - Côte de Nacre
  • Le Mans, France
    • Recruiting
    • Centre Hospitalier Le Mans
  • Nîmes, France, 30029 Cedex 9
    • Active, not recruiting
    • Centre Hospitalier Universitaire de Nîmes
  • Paris, France, 75010
    • Recruiting
    • Hôpital Saint-Louis
  • Poitiers, France
    • Recruiting
    • Centre Hospitalier Universitaire de Poitiers
  • Toulouse, France, 31059
    • Recruiting
    • Institut Universitaire du Cancer de Toulouse Oncopole
  • Villejuif, France, 94800
    • Recruiting
    • Hopital Paul Brousse - Aphp Hôpitaux Universitaires Paris Su
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Universitatsmedizin Berlin
  • Hamburg, Germany, 20251
    • Recruiting
    • UKE - Universitätsklinikum Hamburg-Eppendorf
  • Mainz, Germany
    • Active, not recruiting
    • Universitätsmedizin der Johannes Gutenberg Universität Mainz
  • Mutlangen, Germany, 73557
    • Recruiting
    • Stauferklinikum Schwäbisch Gmünd
  • Saarbrücken, Germany, 66113
    • Recruiting
    • Praxis fur Hamatologie und Onkologie
  • Bayern
    • München, Bayern, Germany, 81675
      • Recruiting
      • Klinikum Rechts der Isar der Technischen Universität München Apotheke
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Active, not recruiting
      • Universitätsklinikum Aachen
    • Essen, Nordrhein-Westfalen, Germany, 45147
      • Recruiting
      • Universitaetsklinikum Essen
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Recruiting
      • Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
    • Dresden, Sachsen, Germany, 01307
      • Recruiting
      • Technische Universitat Dresden
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06120
      • Recruiting
      • Universitätsklinikum Halle
  • Thuringen
    • Jena, Thuringen, Germany, 07747
      • Recruiting
      • Universitätsklinikum Jena
• Greece
  • Patras, Greece, 26504
    • Recruiting
    • University Campus of Patras - Hematology
  • Thessaloníki, Greece, 54636
    • Recruiting
    • AHEPA General Hospital of Thessaloniki
  • Ioannina
    • Ioánnina, Ioannina, Greece, 45500
      • Recruiting
      • University General Hospital of Ioannina
• Hong Kong
  • Hong Kong, Hong Kong, 150001
    • Recruiting
    • Queen Mary Hospital
  • Shatin, Hong Kong
    • Recruiting
    • Prince of Wales Hospital - Medicine
• Hungary
  • Budapest, Hungary
    • Recruiting
    • Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
  • Budapest, Hungary, 1083
    • Withdrawn
    • Semmelweis Egyetem
  • Debrecen, Hungary, 4032
    • Completed
    • Debreceni Egyetem Orvos és Egeszsegtudomanyi Centrum
  • Szeged, Hungary, 6725
    • Recruiting
    • Szegedi Tudományegyetem
  • Somogy
    • Kaposvár, Somogy, Hungary, 7400
      • Withdrawn
      • Somogy Megyei Kaposi Mór Oktató Kórház
  • Szabolcs-Szatmar-Bereg
    • Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary, 4400
      • Recruiting
      • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
  • Vas
    • Szombathely, Vas, Hungary, H-9700
      • Recruiting
      • Markusovszky Egyetemi Oktatokorhaz
• Israel
  • Afula, Israel, 1834111
    • Recruiting
    • Ha'Emek Medical Center
  • Ashdod, Israel
    • Recruiting
    • Assuta Ashdod University Hospital
  • Haifa, Israel, 31096
    • Recruiting
    • Rambam Medical Centre
  • Haifa, Israel
    • Recruiting
    • Carmel MC
  • Jerusalem, Israel, 91120
    • Recruiting
    • Hadassah Medical Organisation
  • Kfar Saba, Israel, 44281
    • Recruiting
    • Hematology Institute
  • Nahariya, Israel, 22100
    • Recruiting
    • Western Galilee Hospital - Nahariya
  • Petah Tikva, Israel, 49100
    • Recruiting
    • Rabin Medical Center - Beilinson Hospital
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky Medical Center - Oncology
  • Tel Aviv, Israel, 64239
    • Recruiting
    • Assuta MC
  • Zerifin, Israel, 7030000
    • Recruiting
    • Assaf Harofeh Medical Center - Hematology
• Italy
  • Alessandria, Italy, 15121
    • Recruiting
    • PO Civile SS.Antonio e Biagio
  • Ancona, Italy, 60123
    • Recruiting
    • AOU Ospedali Riuniti Umberto I G.M. Lancisi G. Salesi
  • Bologna, Italy, 41038
    • Recruiting
    • A.O.di Bologna Policl.S.Orsola
  • Brescia, Italy, 25123
    • Recruiting
    • AO Spedali Civili di Brescia
  • Catania, Italy, 95123
    • Recruiting
    • Azienda Ospedaliero Universitaria Policlinico - Vittorio Emanuele
  • Firenze, Italy, 50141
    • Recruiting
    • AOU Careggi
  • Meldola, Italy
    • Recruiting
    • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST IRCCS
  • Milano, Italy, 20162
    • Recruiting
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milano, Italy, 20122
    • Recruiting
    • Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
  • Novara, Italy, 28100
    • Recruiting
    • AOU Maggiore della Carità
  • Pesaro, Italy, 61121
    • Recruiting
    • Azienda Ospedaliera Ospedali Riuniti Marche Nord - Pesaro
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • Arcispedale S. Maria Nuova, AO di Reggio Emilia
  • Roma, Italy, 00168
    • Recruiting
    • Policlinico Universitario Agostino Gemelli
  • Torino, Italy, 10126
    • Recruiting
    • A.O. Città della Salute e della Scienza di Torino
  • Lombardia
    • Monza, Lombardia, Italy, 20900
      • Recruiting
      • A.O. San Gerardo di Monza - L'Ospedale San Gerardo di Monza e l'Università di Milano
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Recruiting
    • Inje University Busan Paik Hospital
  • Daegu, Korea, Republic of, 42601
    • Recruiting
    • Keimyung University Dongsan Medical Center
  • Daegu, Korea, Republic of, 41944
    • Recruiting
    • Kyungpook National University Hospital
  • Daegu, Korea, Republic of, 42415
    • Recruiting
    • Yeungnam University Medical Center
  • Seongnam-si, Korea, Republic of, Seongnam-si
    • Recruiting
    • CHA Bundang Medical Center, CHA University
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 6591
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
• Lithuania
  • Kaunas, Lithuania, LT-50161
    • Recruiting
    • Hospital of Lithuanian University of Health Sciences Kaunas
• Mexico
  • Monterrey, Mexico, 64180
    • Recruiting
    • Instituto Mexicano del Seguro Social
  • Oaxaca, Mexico, 6800
    • Recruiting
    • Oaxaca Site Management Organization OSMO
  • Veracruz, Mexico, 91910
    • Recruiting
    • Sociedad de Metabolismo y Corazón S.C. - Oncology
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Recruiting
      • Universidad Autonoma de Nuevo Leon (UANL) - Hospital Universitario "Dr. Jose Eleuterio Gonzalez
• Philippines
  • Cebu City, Philippines, 6000
    • Recruiting
    • Perpetual Succour Hospital - Hemat/Transfusion Med
  • Manila, Philippines, 1000
    • Recruiting
    • University of the Philippines - Philippine General Hospital
• Poland
  • Bydgoszcz, Poland, 86-168
    • Recruiting
    • Szpital Uniwersytecki nr 2 im dr. Jana Biziela
  • Lublin, Poland, 20-081
    • Withdrawn
    • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
  • Olsztyn, Poland
    • Recruiting
    • SPZOZ MSWiA z Warminsko - Mazurskim Centrum Onkologii
  • Opole, Poland, 45-061
    • Recruiting
    • Szpital Wojewodzki w Opolu
  • Poznań, Poland, 60-848
    • Withdrawn
    • Clinical Research Center Spółka z Ograniczoną Odpowiedzialnością Medic-R sp. k.
  • Słupsk, Poland, 76-200
    • Recruiting
    • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
  • Dolnoslaskie
    • Wrocław, Dolnoslaskie, Poland, 53-439
      • Recruiting
      • Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
  • Podkarpackie
    • Brzozow, Podkarpackie, Poland, 36-200
      • Active, not recruiting
      • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza
  • Slaskie
    • Chorzów, Slaskie, Poland, 41-500
      • Recruiting
      • Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
• Portugal
  • Aveiro, Portugal, 3814-501
    • Recruiting
    • H. Infante Dom Pedro. Centro Hospitalar do Baixo Vouga
  • Braga, Portugal, 4710-243
    • Recruiting
    • Hospital de Braga
  • Coimbra, Portugal, 3000-075
    • Recruiting
    • Instituto Português de Oncologia de Coimbra
  • Lisboa, Portugal, 1495-005
    • Recruiting
    • H. São Francisco Xavier-Centro Hospitalar Lisboa Ocidental
  • Lisbon, Portugal, 1400-038
    • Recruiting
    • Champalimaud Cancer Center
• Romania
  • Brasov, Romania, 500283
    • Recruiting
    • Cen Med de Diagn si Trat Amb NEOMED
  • Bucharest, Romania, 020125
    • Recruiting
    • Spitalul Clinic Colentina
  • Bucuresti, Romania, 030171
    • Recruiting
    • Spitalul Clinic Coltea
  • Bucuresti, Romania, 060201
    • Recruiting
    • Medicover
  • Cluj-Napoca, Romania, 400015
    • Recruiting
    • Institutul Oncologic "Prof. Dr. Ion Chiricuta"
  • Craiova, Romania, 200143
    • Recruiting
    • Spitalul Clinic Municipal Filantropia Craiova
  • Iaşi, Romania, 700483
    • Recruiting
    • Institutul Regional de Oncologie Iasi
  • Timişoara, Romania, 300079
    • Recruiting
    • Spitalul Clinic Municipal de Urgenta Timisoara
  • Timişoara, Romania, 300329
    • Recruiting
    • Oncomed
  • Târgu-Mureş, Romania, 540136
    • Recruiting
    • Spitalul Clinic Judetean de Urgenta Tg Mures
• Russian Federation
  • Omsk, Russian Federation, 644013
    • Withdrawn
    • Clinical oncological dispensary
  • St Petersburg, Russian Federation, 197089
    • Withdrawn
    • Saint-Petersburg SMU I.P.Pavlov
  • Syktyvkar, Russian Federation, 167904
    • Withdrawn
    • Oncologic Dispensary of Komi Republic
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 8041
    • Recruiting
    • Hospital de La Santa Creu i Sant Pau
  • Cáceres, Spain, 1003
    • Recruiting
    • Hospital San Pedro de Alcántara
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Virgen de la Victoria
  • Palma de Mallorca, Spain, 07120
    • Recruiting
    • Hospital Universitario Son Espases
  • Pamplona, Spain, 31008
    • Recruiting
    • Complejo Hospitalario de Navarra - H. de Navarra, Hematología C/ de Irunlarrea, 3, Pamplona
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Universitario de Salamanca
  • Valencia, Spain, 46017
    • Recruiting
    • Hospital Universitario Doctor Peset
  • Zaragoza, Spain, 50012
    • Recruiting
    • H. Quirón Zaragoza
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • Hospital Universitari Germans Trias i Pujol
  • Las Palmas
    • Las Palmas De Gran Canaria, Las Palmas, Spain, 35010
      • Recruiting
      • Hospital Universitario de Gran Canaria Doctor Negrin
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Active, not recruiting
      • Hospital Universitario Puerta de Hierro - Majadahonda
• Taiwan
  • Chiayi City, Taiwan
    • Recruiting
    • Chang Gung Medical Foundation - ChiaYi Chang Gung Memorial Hospital - Chiayi Branch
  • Kaohsiung, Taiwan, 807
    • Recruiting
    • Kaohsiung Medical University - Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • Recruiting
    • China Medical University Hospital
  • Taipei
    • Taipei City, Taipei, Taiwan, 100
      • Recruiting
      • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Siriraj Hospital
  • Bangkok, Thailand, 10400
    • Recruiting
    • Ramathibodi Hospital - Mahidol University - Hematology
  • Khlong Luang, Thailand, 12120
    • Recruiting
    • Thammasat University Hospital
  • Khon Kaen, Thailand, 40002
    • Recruiting
    • Srinagarind Hospital (KhonKaen University)
  • Songkhla, Thailand, 90110
    • Recruiting
    • Songklanagarind Hospital
• Turkey
  • Adapazarı, Turkey, 54100
    • Recruiting
    • Sakarya Research and Training Hospital
  • Ankara, Turkey, 06500
    • Recruiting
    • Gazi University Medical Faculty
  • Ankara, Turkey, 06500
    • Recruiting
    • Ankara University Faculty of Medicine
  • Denizli, Turkey, 20160
    • Recruiting
    • Pamukkale University
  • Gaziantep, Turkey, 27100
    • Recruiting
    • Gaziantep University Faculty of Medicine
  • Malatya, Turkey, 44280
    • Recruiting
    • Inonu University Turgut Ozal Medical Center
  • Mersin, Turkey, 33110
    • Recruiting
    • Mersin University Medical Faculty
  • Samsun, Turkey, 55280
    • Recruiting
    • Ondokuz Mayis University Medical Faculty - Hematology
• United Kingdom
  • Birmingham, United Kingdom
    • Active, not recruiting
    • University Hospitals Birmingham NHS Foundation Trust
  • Glasgow, United Kingdom
    • Active, not recruiting
    • NHS Greater Glasgow and Clyde
  • London, United Kingdom, SE1 9RT
    • Active, not recruiting
    • Guy's and Saint Thomas' NHS Foundation Trust
  • Oxford, United Kingdom
    • Active, not recruiting
    • Oxford University Hospitals NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Active, not recruiting
      • The Kirklin Clinic of Uab Hospital
  • California
    • Los Angeles, California, United States, 90033
      • Active, not recruiting
      • University of Southern California Norris Comprehensive Cancer Center
    • Stanford, California, United States, 94305
      • Active, not recruiting
      • Stanford Cancer Center - Palo Alto
    • Whittier, California, United States, 90603
      • Completed
      • Innovative Clinical Research Institute
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Withdrawn
      • University Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60611
      • Completed
      • Northwestern University Feinberg School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Withdrawn
      • Dana-Farber Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • New York
    • Brooklyn, New York, United States, 11212
      • Recruiting
      • Brookdale University Hospital and Medical Center
    • New York, New York, United States, 10029
      • Recruiting
      • Mt. Sinai
    • New York, New York, United States, 10021
      • Withdrawn
      • New York Presbyterian/Weill Cornell Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer Center
    • Columbus, Ohio, United States, 43210
      • Completed
      • The Ohio State University Comprehensive Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Completed
      • Oregon Health and Science University
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Recruiting
      • Avera Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin - Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• ECOG ≤ 2

Exclusion Criteria:

• Prior splenectomy
• Splenic irradiation within 3 months prior to randomization
• History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization
• History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization
• Prior MDM2 inhibitor therapy or p53-directed therapy
• Prior allogeneic stem-cell transplant or plans for allogeneic stem cell transplant
• History of major organ transplant
• Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Cohort 1; KRT-232 120 mg 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-232 240 mg 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-232 240 mg 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 A Cohort 4b; KRT-232 240 mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)	Drug: KRT-232; KRT-232, administered by mouth
Experimental: Part B Arm 1 KRT-232; KRT-232 240 mg 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
Active Comparator: Part B Arm 2 Best Available Therapy; Best available therapy at the discretion of the investigator, on a 28-day cycle.	Drug: Best Available Therapy (BAT); Best available therapy options include: hydroxyurea; chemotherapy or; supportive care (including but not limited to corticosteroids and androgens; JAK inhibitors not allowed).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part A Only) Spleen Volume Reduction (SVR)	The proportion of subjects achieving a ≥ 35% spleen volume reduction (SVR) from Baseline to Week 24, as assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scan	24 weeks
(Part B Only) Spleen Volume Reduction (SVR)	The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan (central review)	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part A only) Improvement in Total Symptom Score (TSS)	The proportion of subjects 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	48 weeks
(Part B only) Improvement of Total Symptom Score (TSS)	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	24 Weeks
(Part B only) Overall Survival (OS)	Time from randomization to death from any cause	48 months
(Part B only) Progression free survival (PFS)	Time from randomization to either first occurrence of disease progression or death due to any cause	48 months
(Part B Only) Overall Spleen Volume Reduction (SVR)	The proportion of subjects in each arm achieving SVR of ≥ 35% at any time by MRI/CT scan (central review)	48 months
(Part B Only) Spleen Response Duration	Time from initial SVR of ≥ 35% by MRI/CT (central review) until the first occurrence of disease progression	48 months
(Part B Only) Rate of conversion from RBC transfusion dependent to independent	The proportion of subjects who have RBC transfusion independence at week 24	24 weeks

Collaborators and Investigators

• Sponsor: Kartos Therapeutics, Inc.

Publications and helpful links

General Publications

• Al-Ali, H.K.; Delgado, R.G.; Lange, A.; Pluta, A.; McLornan, D.; Vachhani, P.; Damaj, G.L.; Jost, P.J.; Rejto, L.; Hus, M.; et al. KRT-232, A First-In-Class, Murine Double Minute 2 Inhibitor, for Myelofibrosis Relapsed or Refractory to Janus-Associated Kinase Inhibitor Treatment. Eha. Libr. 2020, 295035, S215

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 7, 2018

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: navtemadlin
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: KRT-232-101

Drug and device information, study documents

• 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