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
1 other identifier
interventional
385
28 countries
191
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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2019
Longer than P75 for phase_2
191 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 5, 2018
CompletedFirst Posted
Study publicly available on registry
September 7, 2018
CompletedStudy Start
First participant enrolled
January 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2025
CompletedApril 28, 2023
April 1, 2023
5 years
September 5, 2018
April 26, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
(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 Outcomes (7)
(Part A only) Improvement in Total Symptom Score (TSS)
48 weeks
(Part B only) Improvement of Total Symptom Score (TSS)
24 Weeks
(Part B only) Overall Survival (OS)
48 months
(Part B only) Progression free survival (PFS)
48 months
(Part B Only) Overall Spleen Volume Reduction (SVR)
48 months
- +2 more secondary outcomes
Study Arms (6)
Part A Cohort 1
EXPERIMENTALKRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Part A Cohort 2
EXPERIMENTALKRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Part A Cohort 3
EXPERIMENTALKRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Part A Cohort 4b
EXPERIMENTALKRT-232 240 mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)
Part B Arm 1 KRT-232
EXPERIMENTALKRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Part B Arm 2 Best Available Therapy
ACTIVE COMPARATORBest available therapy at the discretion of the investigator, on a 28-day cycle.
Interventions
KRT-232, administered by mouth
Best available therapy options include: 1. hydroxyurea 2. chemotherapy or 3. supportive care (including but not limited to corticosteroids and androgens; JAK inhibitors not allowed).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (191)
The Kirklin Clinic of UAB Hospital
Birmingham, Alabama, 35294, United States
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Stanford Cancer Center - Palo Alto
Stanford, California, 94305, United States
Innovative Clinical Research Institute
Whittier, California, 90603, United States
University Cancer Institute
Boynton Beach, Florida, 33426, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
University of Illinois at Chicago
Chicago, Illinois, 60612, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Brookdale University Hospital and Medical Center
Brooklyn, New York, 11212, United States
New York Presbyterian/Weill Cornell Medical Center
New York, New York, 10021, United States
Mt. Sinai
New York, New York, 10029, United States
Gabrail Cancer Center
Canton, Ohio, 44718, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37203, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Medical College of Wisconsin - Froedtert Hospital
Milwaukee, Wisconsin, 53226, United States
Sanatorio de la Mujer
Rosario, Santa Fe Province, S2000ORE, Argentina
Instituto Medico Alexander Fleming
Buenos Aires, Argentina
Centro Medico San Luis
CABA, 1425, Argentina
Hospital Privado - Centro Medico de Cordoba - Oncology
Córdoba, X5016KEH, Argentina
Monash Medical Centre
Clayton, Victoria, 3168, Australia
Fiona Stanley Hosital
Murdoch, Western Australia, 6150, Australia
Royal Adelaide Hospital
Adelaide, Australia
The Alfred Hospital
Melbourne, Australia
South Eastern Private Hospital
Noble Park, 3174, Australia
Icon Cancer Center
South Brisbane, Australia
Centro de oncologia Leonardo da Vinci
Fortaleza, Ceará, 60140-025, Brazil
Hospital Erasto Gaertner
Curitiba, Paraná, 81520, Brazil
UNICAMP - Universidade Estadual de Campinas Hemocentro
Campinas, São Paulo, 13083, Brazil
Hospital das Clínicas UFG
Goiânia, 74605, Brazil
Fundacao Doutor Amaral Carvalho
Jaú, 17210-120, Brazil
Hospital de Clinicas de Porto Alegre - Centro de Pesquisa Clinica
Porto Alegre, 90035-903, Brazil
Associação Educadora São Carlos AESC - Hospital Mãe de Deus - Centro de Pesquisa
Porto Alegre, 90880-480, Brazil
Instituto de Ensino e Pesquisa São Lucas
São Paulo, 01236-030, Brazil
Hospital A C Camargo - Fundacao Antonio Prudente
São Paulo, 01509-900, Brazil
Instituto D'or de Pesquisa e Ensino
São Paulo, 04502-001, Brazil
Hospital das Clínicas da Universidade de São Paulo
São Paulo, 05403-000, Brazil
Instituto COI São Paulo
São Paulo, 1321001, Brazil
University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven
Pleven, Bulgaria
University Multiprofile Hospital for Active Treatment Sveti Georgi, Plovdiv
Plovdiv, Bulgaria
Military Medical Academy, Multiprofile for active treatment, Sofia
Sofia, 1606, Bulgaria
Acibadem City Clinic Tokuda Hospital, Sofia
Sofia, Bulgaria
Specialized Hospital for Active Therapy of Hematological Disorders
Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment Alexandrovska, Sofia
Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment Saint Ivan Rilski, Sofia
Sofia, Bulgaria
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9, Canada
General Hospital Sibenik
Šibenik, 22000, Croatia
Clinical Hospital Centre Osijek
Zagreb, 10000, Croatia
KB Sestre Milosrdnice
Zagreb, 10000, Croatia
FN Hradec Kralove
Králová, 500 05, Czechia
Vseonecma fakultni nemocrince V Praze
New Town, Czechia
Fakultní Nemocnice Olomouc
Olomouc, 779 00, Czechia
Centre Hospitalier Universitaire D'Amiens (Hopital Sud) - Hématologie Clinique
Amiens, 80054, France
Center Hospitalier Universitaire d'Angers
Angers, 49933 Cedex 09, France
C.H de la Côte Basque - Serviv
Bayonne, 64100, France
Centre Hospitalier Regional Universitaire Brest Hopital Morvan
Brest, 29609, France
Centre Hospitalier Universitaire of Caen Normandie - Côte de Nacre
Caen, 14000, France
Centre Hospitalier Le Mans
Le Mans, France
Centre Hospitalier Universitaire de Nîmes
Nîmes, 30029 Cedex 9, France
Hôpital Saint-Louis
Paris, 75010, France
Centre Hospitalier Universitaire de Poitiers
Poitiers, France
Institut Universitaire du Cancer de Toulouse Oncopole
Toulouse, 31059, France
Hopital Paul Brousse - Aphp Hôpitaux Universitaires Paris Su
Villejuif, 94800, France
Klinikum Rechts der Isar der Technischen Universität München Apotheke
München, Bavaria, 81675, Germany
Universitätsklinikum Aachen
Aachen, North Rhine-Westphalia, 52074, Germany
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45147, Germany
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
Dresden, Saxony, 01307, Germany
Technische Universität Dresden
Dresden, Saxony, 01307, Germany
Universitätsklinikum Halle
Halle, Saxony-Anhalt, 06120, Germany
Universitätsklinikum Jena
Jena, Thuringia, 07747, Germany
Charité Universitätsmedizin Berlin
Berlin, 13353, Germany
UKE - Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20251, Germany
Universitätsmedizin der Johannes Gutenberg Universität Mainz
Mainz, Germany
Stauferklinikum Schwäbisch Gmünd
Mutlangen, 73557, Germany
Praxis für Hämatologie und Onkologie
Saarbrücken, 66113, Germany
University General Hospital of Ioannina
Ioannina, Ioannina, 45500, Greece
University Campus of Patras - Hematology
Pátrai, 26504, Greece
AHEPA General Hospital of Thessaloniki
Thessaloniki, 54636, Greece
Queen Mary Hospital
Hong Kong, 150001, Hong Kong
Prince of Wales Hospital - Medicine
Shatin, Hong Kong
Somogy Megyei Kaposi Mór Oktató Kórház
Kaposvár, Somogy County, 7400, Hungary
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary
Markusovszky Egyetemi Oktatókórház
Szombathely, Vas County, H-9700, Hungary
Semmelweis Egyetem
Budapest, 1083, Hungary
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
Budapest, Hungary
Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
Debrecen, 4032, Hungary
Szegedi Tudományegyetem
Szeged, 6725, Hungary
Ha'Emek Medical Center
Afula, 1834111, Israel
Assuta Ashdod University Hospital
Ashdod, Israel
Rambam Medical Centre
Haifa, 31096, Israel
Carmel MC
Haifa, Israel
Hadassah Medical Organisation
Jerusalem, 91120, Israel
Hematology Institute
Kfar Saba, 44281, Israel
Western Galilee Hospital - Nahariya
Nahariya, 22100, Israel
Rabin Medical Center - Beilinson Hospital
Petah Tikva, 49100, Israel
Tel Aviv Sourasky Medical Center - Oncology
Tel Aviv, 6423906, Israel
Assuta MC
Tel Aviv, 64239, Israel
Assaf Harofeh Medical Center - Hematology
Ẕerifin, 7030000, Israel
A.O. San Gerardo di Monza - L'Ospedale San Gerardo di Monza e l'Università di Milano
Monza, Lombardy, 20900, Italy
PO Civile SS.Antonio e Biagio
Alessandria, 15121, Italy
AOU Ospedali Riuniti Umberto I G.M. Lancisi G. Salesi
Ancona, 60123, Italy
A.O.di Bologna Policl.S.Orsola
Bologna, 41038, Italy
AO Spedali Civili di Brescia
Brescia, 25123, Italy
Azienda Ospedaliero Universitaria Policlinico - Vittorio Emanuele
Catania, 95123, Italy
AOU Careggi
Florence, 50141, Italy
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST IRCCS
Meldola, Italy
Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
Milan, 20122, Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162, Italy
AOU Maggiore della Carità
Novara, 28100, Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord - Pesaro
Pesaro, 61121, Italy
Arcispedale S. Maria Nuova, AO di Reggio Emilia
Reggio Emilia, 42123, Italy
Policlinico Universitario Agostino Gemelli
Roma, 00168, Italy
A.O. Citta della Salute e della Scienza di Torino
Torino, 10126, Italy
Hospital of Lithuanian University of Health Sciences Kaunas
Kaunas, LT-50161, Lithuania
Universidad Autonoma de Nuevo Leon (UANL) - Hospital Universitario "Dr. Jose Eleuterio Gonzalez
Monterrey, Nuevo León, 64460, Mexico
Instituto Mexicano del Seguro Social
Monterrey, 64180, Mexico
Oaxaca Site Management Organization OSMO
Oaxaca City, 6800, Mexico
Sociedad de Metabolismo y Corazón S.C. - Oncology
Veracruz, 91910, Mexico
Perpetual Succour Hospital - Hemat/Transfusion Med
Cebu City, 6000, Philippines
University of the Philippines - Philippine General Hospital
Manila, 1000, Philippines
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
Wroclaw, Lower Silesian Voivodeship, 53-439, Poland
Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
Brzozów, Podkarpackie Voivodeship, 36-200, Poland
Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
Chorzów, Silesian Voivodeship, 41-500, Poland
Szpital Uniwersytecki nr 2 im dr. Jana Biziela
Bydgoszcz, 86-168, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin, 20-081, Poland
SPZOZ MSWiA z Warminsko - Mazurskim Centrum Onkologii
Olsztyn, Poland
Szpital Wojewódzki w Opolu
Opole, 45-061, Poland
Clinical Research Center Spółka z Ograniczoną Odpowiedzialnością Medic-R sp. k.
Poznan, 60-848, Poland
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
Słupsk, 76-200, Poland
H. Infante Dom Pedro. Centro Hospitalar do Baixo Vouga
Aveiro, 3814-501, Portugal
Hospital de Braga
Braga, 4710-243, Portugal
Instituto Português de Oncologia de Coimbra
Coimbra, 3000-075, Portugal
Champalimaud Cancer Center
Lisbon, 1400-038, Portugal
H. São Francisco Xavier-Centro Hospitalar Lisboa Ocidental
Lisbon, 1495-005, Portugal
Cen Med de Diagn si Trat Amb NEOMED
Brasov, 500283, Romania
Spitalul Clinic Colentina
Bucharest, 020125, Romania
Spitalul Clinic Coltea
Bucharest, 030171, Romania
Medicover
Bucharest, 060201, Romania
Institutul Oncologic "Prof. Dr. Ion Chiricuta"
Cluj-Napoca, 400015, Romania
Spitalul Clinic Municipal Filantropia Craiova
Craiova, 200143, Romania
Institutul Regional de Oncologie Iasi
Iași, 700483, Romania
Spitalul Clinic Judetean de Urgenta Tg Mures
Târgu Mureş, 540136, Romania
Spitalul Clinic Municipal de Urgenta Timisoara
Timișoara, 300079, Romania
Oncomed
Timișoara, 300329, Romania
Clinical oncological dispensary
Omsk, 644013, Russia
Saint-Petersburg SMU I.P.Pavlov
Saint Petersburg, 197089, Russia
Oncologic dispensary of Komi Republic
Syktyvkar, 167904, Russia
Inje University Busan Paik Hospital
Busan, 47392, South Korea
Kyungpook National University Hospital
Daegu, 41944, South Korea
Yeungnam University Medical Center
Daegu, 42415, South Korea
Keimyung University Dongsan Medical Center
Daegu, 42601, South Korea
CHA Bundang Medical Center, CHA University
Seongnam-si, Seongnam-si, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 6591, South Korea
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916, Spain
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, Las Palmas, 35010, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, Madrid, 28222, Spain
Hospital Universitario Vall d'Hebrón
Barcelona, 08035, Spain
Hospital de La Santa Creu i Sant Pau
Barcelona, 8041, Spain
Hospital San Pedro de Alcantara
Cáceres, 1003, Spain
Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Hospital Universitario Son Espases
Palma de Mallorca, 07120, Spain
Complejo Hospitalario de Navarra - H. de Navarra, Hematología C/ de Irunlarrea, 3, Pamplona
Pamplona, 31008, Spain
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Universitario Doctor Peset
Valencia, 46017, Spain
H. Quirón Zaragoza
Zaragoza, 50012, Spain
National Taiwan University Hospital
Taipei City, Taipei, 100, Taiwan
Chang Gung Medical Foundation - ChiaYi Chang Gung Memorial Hospital - Chiayi Branch
Chiayi City, Taiwan
Kaohsiung Medical University - Chung-Ho Memorial Hospital
Kaohsiung City, 807, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
Ramathibodi Hospital - Mahidol University - Hematology
Bangkok, 10400, Thailand
Siriraj Hospital
Bangkok, 10700, Thailand
Thammasat University Hospital
Khlong Luang, 12120, Thailand
Srinagarind Hospital (KhonKaen University)
Khon Kaen, 40002, Thailand
Songklanagarind Hospital
Songkhla, 90110, Thailand
Sakarya Research and Training Hospital
Adapazarı, 54100, Turkey (Türkiye)
Ankara University Faculty of Medicine
Ankara, 06500, Turkey (Türkiye)
Gazi University Medical Faculty
Ankara, 06500, Turkey (Türkiye)
Pamukkale University
Denizli, 20160, Turkey (Türkiye)
Gaziantep University Faculty of Medicine
Gaziantep, 27100, Turkey (Türkiye)
Inonu University Turgut Ozal Medical Center
Malatya, 44280, Turkey (Türkiye)
Mersin University Medical Faculty
Mersin, 33110, Turkey (Türkiye)
Ondokuz Mayis University Medical Faculty - Hematology
Samsun, 55280, Turkey (Türkiye)
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
NHS Greater Glasgow and Clyde
Glasgow, United Kingdom
Guy's and Saint Thomas' NHS Foundation Trust
London, SE1 9RT, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Related Publications (1)
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
BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 5, 2018
First Posted
September 7, 2018
Study Start
January 15, 2019
Primary Completion
December 31, 2023
Study Completion
December 31, 2025
Last Updated
April 28, 2023
Record last verified: 2023-04