KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment (BOREAS)
Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF)
About this trial
This is an interventional treatment trial for Primary Myelofibrosis (PMF) focused on measuring navtemadlin
Eligibility 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
- 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)
Sites / Locations
- The Kirklin Clinic of UAB Hospital
- University of Southern California Norris Comprehensive Cancer Center
- Stanford Cancer Center - Palo Alto
- Innovative Clinical Research Institute
- University Cancer Institute
- Northwestern University Feinberg School of Medicine
- University of Illinois at ChicagoRecruiting
- Dana-Farber Cancer Institute
- Washington University School of MedicineRecruiting
- Brookdale University Hospital and Medical CenterRecruiting
- New York Presbyterian/Weill Cornell Medical Center
- Mt. SinaiRecruiting
- Gabrail Cancer CenterRecruiting
- The Ohio State University Comprehensive Cancer Center
- Oregon Health and Science University
- Avera Cancer InstituteRecruiting
- Vanderbilt University Medical CenterRecruiting
- The University of Texas MD Anderson Cancer CenterRecruiting
- Medical College of Wisconsin - Froedtert HospitalRecruiting
- Sanatorio de la MujerRecruiting
- Instituto Medico Alexander FlemingRecruiting
- Centro Medico San LuisRecruiting
- Hospital Privado - Centro Medico de Cordoba - OncologyRecruiting
- Monash Medical CentreRecruiting
- Fiona Stanley HositalRecruiting
- Royal Adelaide HospitalRecruiting
- The Alfred HospitalRecruiting
- South Eastern Private HospitalRecruiting
- Icon Cancer CenterRecruiting
- Centro de oncologia Leonardo da VinciRecruiting
- Hospital Erasto GaertnerRecruiting
- UNICAMP - Universidade Estadual de Campinas HemocentroRecruiting
- Hospital das Clínicas UFGRecruiting
- Fundacao Doutor Amaral CarvalhoRecruiting
- Hospital de Clinicas de Porto Alegre - Centro de Pesquisa ClinicaRecruiting
- Associação Educadora São Carlos AESC - Hospital Mãe de Deus - Centro de PesquisaRecruiting
- Instituto de Ensino e Pesquisa São LucasRecruiting
- Hospital A C Camargo - Fundacao Antonio PrudenteRecruiting
- Hospital das Clínicas da Universidade de São PauloRecruiting
- Instituto D'or de Pesquisa e EnsinoRecruiting
- Instituto COI São PauloRecruiting
- University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, PlevenRecruiting
- University Multiprofile Hospital for Active Treatment Sveti Georgi, PlovdivRecruiting
- Military Medical Academy, Multiprofile for active treatment, SofiaRecruiting
- Acibadem City Clinic Tokuda Hospital, SofiaRecruiting
- Specialized Hospital for Active Therapy of Hematological DisordersRecruiting
- University Multiprofile Hospital for Active Treatment Alexandrovska, Sofia
- University Multiprofile Hospital for Active Treatment Saint Ivan Rilski, SofiaRecruiting
- Princess Margaret Cancer Center
- General Hospital SibenikRecruiting
- Clinical Hospital Centre OsijekRecruiting
- KB Sestre MilosrdniceRecruiting
- FN Hradec KraloveRecruiting
- Vseonecma fakultni nemocrince V PrazeRecruiting
- Fakultní Nemocnice Olomouc
- Centre Hospitalier Universitaire D'Amiens (Hopital Sud) - Hématologie CliniqueRecruiting
- Center Hospitalier Universitaire d'AngersRecruiting
- C.H de la Côte Basque - ServivRecruiting
- Centre Hospitalier Regional Universitaire Brest Hopital MorvanRecruiting
- Centre Hospitalier Universitaire of Caen Normandie - Côte de Nacre
- Centre Hospitalier Le MansRecruiting
- Centre Hospitalier Universitaire de Nîmes
- Hôpital Saint-LouisRecruiting
- Centre Hospitalier Universitaire de PoitiersRecruiting
- Institut Universitaire du Cancer de Toulouse OncopoleRecruiting
- Hopital Paul Brousse - Aphp Hôpitaux Universitaires Paris SuRecruiting
- Klinikum Rechts der Isar der Technischen Universität München ApothekeRecruiting
- Universitätsklinikum Aachen
- Universitaetsklinikum EssenRecruiting
- Universitätsklinikum HalleRecruiting
- Gemeinschaftspraxis Haematologie - Onkologie - HauptstelleRecruiting
- Technische Universität DresdenRecruiting
- Universitätsklinikum JenaRecruiting
- Charité Universitätsmedizin BerlinRecruiting
- UKE - Universitätsklinikum Hamburg-EppendorfRecruiting
- Universitätsmedizin der Johannes Gutenberg Universität Mainz
- Stauferklinikum Schwäbisch GmündRecruiting
- Praxis für Hämatologie und OnkologieRecruiting
- University General Hospital of IoanninaRecruiting
- University Campus of Patras - HematologyRecruiting
- AHEPA General Hospital of ThessalonikiRecruiting
- Queen Mary HospitalRecruiting
- Prince of Wales Hospital - MedicineRecruiting
- Somogy Megyei Kaposi Mór Oktató Kórház
- Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi OktatókórházRecruiting
- Markusovszky Egyetemi OktatókórházRecruiting
- Semmelweis Egyetem
- Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai IntézetRecruiting
- Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
- Szegedi TudományegyetemRecruiting
- Ha'Emek Medical CenterRecruiting
- Assuta Ashdod University HospitalRecruiting
- Rambam Medical CentreRecruiting
- Carmel MCRecruiting
- Hadassah Medical OrganisationRecruiting
- Hematology InstituteRecruiting
- Western Galilee Hospital - NahariyaRecruiting
- Rabin Medical Center - Beilinson HospitalRecruiting
- Tel Aviv Sourasky Medical Center - OncologyRecruiting
- Assuta MCRecruiting
- Assaf Harofeh Medical Center - HematologyRecruiting
- A.O. San Gerardo di Monza - L'Ospedale San Gerardo di Monza e l'Università di MilanoRecruiting
- PO Civile SS.Antonio e BiagioRecruiting
- AOU Ospedali Riuniti Umberto I G.M. Lancisi G. SalesiRecruiting
- A.O.di Bologna Policl.S.OrsolaRecruiting
- AO Spedali Civili di BresciaRecruiting
- Azienda Ospedaliero Universitaria Policlinico - Vittorio EmanueleRecruiting
- AOU CareggiRecruiting
- Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST IRCCSRecruiting
- Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' GrandaRecruiting
- ASST Grande Ospedale Metropolitano NiguardaRecruiting
- AOU Maggiore della CaritàRecruiting
- Azienda Ospedaliera Ospedali Riuniti Marche Nord - PesaroRecruiting
- Arcispedale S. Maria Nuova, AO di Reggio EmiliaRecruiting
- Policlinico Universitario Agostino GemelliRecruiting
- A.O. Citta della Salute e della Scienza di TorinoRecruiting
- Inje University Busan Paik HospitalRecruiting
- Kyungpook National University HospitalRecruiting
- Yeungnam University Medical CenterRecruiting
- Keimyung University Dongsan Medical CenterRecruiting
- CHA Bundang Medical Center, CHA UniversityRecruiting
- Seoul National University HospitalRecruiting
- Samsung Medical CenterRecruiting
- The Catholic University of Korea, Seoul St. Mary's HospitalRecruiting
- Hospital of Lithuanian University of Health Sciences KaunasRecruiting
- Universidad Autonoma de Nuevo Leon (UANL) - Hospital Universitario "Dr. Jose Eleuterio GonzalezRecruiting
- Instituto Mexicano del Seguro SocialRecruiting
- Oaxaca Site Management Organization OSMORecruiting
- Sociedad de Metabolismo y Corazón S.C. - OncologyRecruiting
- Perpetual Succour Hospital - Hemat/Transfusion MedRecruiting
- University of the Philippines - Philippine General HospitalRecruiting
- Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców SzpikuRecruiting
- Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
- Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali MiejskichRecruiting
- Szpital Uniwersytecki nr 2 im dr. Jana BizielaRecruiting
- Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
- SPZOZ MSWiA z Warminsko - Mazurskim Centrum OnkologiiRecruiting
- Szpital Wojewódzki w OpoluRecruiting
- Clinical Research Center Spółka z Ograniczoną Odpowiedzialnością Medic-R sp. k.
- Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.Recruiting
- H. Infante Dom Pedro. Centro Hospitalar do Baixo VougaRecruiting
- Hospital de BragaRecruiting
- Instituto Português de Oncologia de CoimbraRecruiting
- H. São Francisco Xavier-Centro Hospitalar Lisboa OcidentalRecruiting
- Champalimaud Cancer CenterRecruiting
- Cen Med de Diagn si Trat Amb NEOMEDRecruiting
- Spitalul Clinic ColentinaRecruiting
- Spitalul Clinic ColteaRecruiting
- MedicoverRecruiting
- Institutul Oncologic "Prof. Dr. Ion Chiricuta"Recruiting
- Spitalul Clinic Municipal Filantropia CraiovaRecruiting
- Institutul Regional de Oncologie IasiRecruiting
- Spitalul Clinic Municipal de Urgenta TimisoaraRecruiting
- OncomedRecruiting
- Spitalul Clinic Judetean de Urgenta Tg MuresRecruiting
- Clinical oncological dispensary
- Saint-Petersburg SMU I.P.Pavlov
- Oncologic dispensary of Komi Republic
- Hospital Universitari Germans Trias i PujolRecruiting
- Hospital Universitario de Gran Canaria Doctor NegrinRecruiting
- Hospital Universitario Puerta de Hierro - Majadahonda
- Hospital Universitario Vall d'HebrónRecruiting
- Hospital de La Santa Creu i Sant PauRecruiting
- Hospital San Pedro de AlcantaraRecruiting
- Hospital Universitario Virgen de la VictoriaRecruiting
- Hospital Universitario Son EspasesRecruiting
- Complejo Hospitalario de Navarra - H. de Navarra, Hematología C/ de Irunlarrea, 3, PamplonaRecruiting
- Hospital Universitario de SalamancaRecruiting
- Hospital Universitario Doctor PesetRecruiting
- H. Quirón ZaragozaRecruiting
- National Taiwan University HospitalRecruiting
- Chang Gung Medical Foundation - ChiaYi Chang Gung Memorial Hospital - Chiayi BranchRecruiting
- Kaohsiung Medical University - Chung-Ho Memorial HospitalRecruiting
- China Medical University HospitalRecruiting
- Ramathibodi Hospital - Mahidol University - HematologyRecruiting
- Siriraj HospitalRecruiting
- Thammasat University HospitalRecruiting
- Srinagarind Hospital (KhonKaen University)Recruiting
- Songklanagarind HospitalRecruiting
- Sakarya Research and Training HospitalRecruiting
- Ankara University Faculty of MedicineRecruiting
- Gazi University Medical FacultyRecruiting
- Pamukkale UniversityRecruiting
- Gaziantep University Faculty of MedicineRecruiting
- Inonu University Turgut Ozal Medical CenterRecruiting
- Mersin University Medical FacultyRecruiting
- Ondokuz Mayis University Medical Faculty - HematologyRecruiting
- University Hospitals Birmingham NHS Foundation Trust
- NHS Greater Glasgow and Clyde
- Guy's and Saint Thomas' NHS Foundation Trust
- Oxford University Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Active Comparator
Part A Cohort 1
Part A Cohort 2
Part A Cohort 3
Part A Cohort 4b
Part B Arm 1 KRT-232
Part B Arm 2 Best Available Therapy
KRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
KRT-232 240 mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Best available therapy at the discretion of the investigator, on a 28-day cycle.