KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment
- Conditions
- Primary Myelofibrosis (PMF)Post-Polycythemia Vera MF (Post-PV-MF)Post-Essential Thrombocythemia MF (Post-ET-MF)
- Interventions
- Drug: Best Available Therapy (BAT)
- Registration Number
- NCT03662126
- Lead Sponsor
- 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 385
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part A Cohort 3 KRT-232 KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) Part A Cohort 4b KRT-232 KRT-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 KRT-232 KRT-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 Best Available Therapy (BAT) Best available therapy at the discretion of the investigator, on a 28-day cycle. Part A Cohort 1 KRT-232 KRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) Part A Cohort 2 KRT-232 KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
- Primary Outcome Measures
Name Time Method (Part A Only) Spleen Volume Reduction (SVR) 24 weeks 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
(Part B Only) Spleen Volume Reduction (SVR) 24 Weeks The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan (central review)
- Secondary Outcome Measures
Name Time Method (Part A only) Improvement in Total Symptom Score (TSS) 48 weeks 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
(Part B only) Improvement of Total Symptom Score (TSS) 24 Weeks 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
(Part B Only) Overall Spleen Volume Reduction (SVR) 48 months The proportion of subjects in each arm achieving SVR of ≥ 35% at any time by MRI/CT scan (central review)
(Part B only) Overall Survival (OS) 48 months Time from randomization to death from any cause
(Part B only) Progression free survival (PFS) 48 months Time from randomization to either first occurrence of disease progression or death due to any cause
(Part B Only) Spleen Response Duration 48 months Time from initial SVR of ≥ 35% by MRI/CT (central review) until the first occurrence of disease progression
(Part B Only) Rate of conversion from RBC transfusion dependent to independent 24 weeks The proportion of subjects who have RBC transfusion independence at week 24
Trial Locations
- Locations (191)
University Campus of Patras - Hematology
🇬🇷Patras, Greece
University General Hospital of Ioannina
🇬🇷Ioánnina, Ioannina, Greece
Sanatorio de la Mujer
🇦🇷Rosario, Santa Fe, Argentina
UNICAMP - Universidade Estadual de Campinas Hemocentro
🇧🇷Campinas, São Paulo, Brazil
South Eastern Private Hospital
🇦🇺Noble Park, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Centro Medico San Luis
🇦🇷Caba, Argentina
Icon Cancer Center
🇦🇺South Brisbane, Australia
Centro de oncologia Leonardo da Vinci
🇧🇷Fortaleza, Ceara, Brazil
Clinical Hospital Centre Osijek
🇭🇷Zagreb, Croatia
Vseonecma fakultni nemocrince V Praze
🇨🇿Nové Město, Czechia
Fakultní Nemocnice Olomouc
🇨🇿Olomouc, Czechia
University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven
🇧🇬Pleven, Bulgaria
Hospital de Clinicas de Porto Alegre - Centro de Pesquisa Clinica
🇧🇷Porto Alegre, Brazil
Fundacao Doutor Amaral Carvalho
🇧🇷Jau, Brazil
Centre Hospitalier Universitaire D'Amiens (Hopital Sud) - Hématologie Clinique
🇫🇷Amiens, France
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
AO Spedali Civili di Brescia
🇮🇹Brescia, Italy
Prince of Wales Hospital - Medicine
🇭🇰Shatin, Hong Kong
AHEPA General Hospital of Thessaloniki
🇬🇷Thessaloníki, Greece
Stauferklinikum Schwäbisch Gmünd
🇩🇪Mutlangen, Germany
Praxis für Hämatologie und Onkologie
🇩🇪Saarbrücken, Germany
Hospital das Clínicas UFG
🇧🇷Goiânia, Brazil
Centre Hospitalier Universitaire de Nîmes
🇫🇷Nîmes, France
Markusovszky Egyetemi Oktatókórház
🇭🇺Szombathely, Vas, Hungary
Centre Hospitalier Universitaire of Caen Normandie - Côte de Nacre
🇫🇷Caen, France
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
🇭🇺Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary
Acibadem City Clinic Tokuda Hospital, Sofia
🇧🇬Sofia, Bulgaria
FN Hradec Kralove
🇨🇿Králová, Czechia
Specialized Hospital for Active Therapy of Hematological Disorders
🇧🇬Sofia, Bulgaria
A.O.di Bologna Policl.S.Orsola
🇮🇹Bologna, Italy
Szegedi Tudományegyetem
🇭🇺Szeged, Hungary
Rambam Medical Centre
🇮🇱Haifa, Israel
Universitätsmedizin der Johannes Gutenberg Universität Mainz
🇩🇪Mainz, Germany
C.H de la Côte Basque - Serviv
🇫🇷Bayonne, France
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
🇩🇪Dresden, Sachsen, Germany
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Universitätsklinikum Aachen
🇩🇪Aachen, Nordrhein-Westfalen, Germany
Klinikum Rechts der Isar der Technischen Universität München Apotheke
🇩🇪München, Bayern, Germany
Hôpital Saint-Louis
🇫🇷Paris, France
PO Civile SS.Antonio e Biagio
🇮🇹Alessandria, Italy
Universitätsklinikum Halle
🇩🇪Halle, Sachsen-Anhalt, Germany
Assaf Harofeh Medical Center - Hematology
🇮🇱Zerifin, Israel
Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
🇭🇺Debrecen, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Hospital of Lithuanian University of Health Sciences Kaunas
🇱🇹Kaunas, Lithuania
Oaxaca Site Management Organization OSMO
🇲🇽Oaxaca, Mexico
Sociedad de Metabolismo y Corazón S.C. - Oncology
🇲🇽Veracruz, Mexico
Spitalul Clinic Colentina
🇷🇴Bucharest, Romania
Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
🇵🇱Brzozow, Podkarpackie, Poland
Szpital Wojewódzki w Opolu
🇵🇱Opole, Poland
Western Galilee Hospital - Nahariya
🇮🇱Nahariya, Israel
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
🇭🇺Budapest, Hungary
Hospital de Braga
🇵🇹Braga, Portugal
Champalimaud Cancer Center
🇵🇹Lisbon, Portugal
Spitalul Clinic Municipal Filantropia Craiova
🇷🇴Craiova, Romania
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱Lublin, Poland
SPZOZ MSWiA z Warminsko - Mazurskim Centrum Onkologii
🇵🇱Olsztyn, Poland
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Tel Aviv Sourasky Medical Center - Oncology
🇮🇱Tel Aviv, Israel
Rabin Medical Center - Beilinson Hospital
🇮🇱Petah Tikva, Israel
Hematology Institute
🇮🇱Kfar Saba, Israel
AOU Ospedali Riuniti Umberto I G.M. Lancisi G. Salesi
🇮🇹Ancona, Italy
Institutul Oncologic "Prof. Dr. Ion Chiricuta"
🇷🇴Cluj-Napoca, Romania
Universidad Autonoma de Nuevo Leon (UANL) - Hospital Universitario "Dr. Jose Eleuterio Gonzalez
🇲🇽Monterrey, Nuevo Leon, Mexico
Perpetual Succour Hospital - Hemat/Transfusion Med
🇵🇭Cebu City, Philippines
Hadassah Medical Organisation
🇮🇱Jerusalem, Israel
CHA Bundang Medical Center, CHA University
🇰🇷Seongnam-si, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
H. São Francisco Xavier-Centro Hospitalar Lisboa Ocidental
🇵🇹Lisboa, Portugal
Cen Med de Diagn si Trat Amb NEOMED
🇷🇴Brasov, Romania
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
🇵🇱Chorzów, Slaskie, Poland
Szpital Uniwersytecki nr 2 im dr. Jana Biziela
🇵🇱Bydgoszcz, Poland
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
🇵🇱Słupsk, Poland
University of the Philippines - Philippine General Hospital
🇵🇭Manila, Philippines
Instituto Português de Oncologia de Coimbra
🇵🇹Coimbra, Portugal
Spitalul Clinic Coltea
🇷🇴Bucuresti, Romania
Institutul Regional de Oncologie Iasi
🇷🇴Iaşi, Romania
China Medical University Hospital
🇨🇳Taichung, Taiwan
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
🇵🇱Wrocław, Dolnoslaskie, Poland
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Oncologic dispensary of Komi Republic
🇷🇺Syktyvkar, Russian Federation
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Instituto Mexicano del Seguro Social
🇲🇽Monterrey, Mexico
Clinical Research Center Spółka z Ograniczoną Odpowiedzialnością Medic-R sp. k.
🇵🇱Poznań, Poland
H. Infante Dom Pedro. Centro Hospitalar do Baixo Vouga
🇵🇹Aveiro, Portugal
Medicover
🇷🇴Bucuresti, Romania
Spitalul Clinic Municipal de Urgenta Timisoara
🇷🇴Timişoara, Romania
Srinagarind Hospital (KhonKaen University)
🇹🇭Khon Kaen, Thailand
Saint-Petersburg SMU I.P.Pavlov
🇷🇺St Petersburg, Russian Federation
Clinical oncological dispensary
🇷🇺Omsk, Russian Federation
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Oncomed
🇷🇴Timişoara, Romania
Spitalul Clinic Judetean de Urgenta Tg Mures
🇷🇴Târgu-Mureş, Romania
Chang Gung Medical Foundation - ChiaYi Chang Gung Memorial Hospital - Chiayi Branch
🇨🇳Chiayi City, Taiwan
Songklanagarind Hospital
🇹🇭Songkhla, Thailand
Hospital Universitario de Gran Canaria Doctor Negrin
🇪🇸Las Palmas De Gran Canaria, Las Palmas, Spain
Hospital de La Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebrón
🇪🇸Barcelona, Spain
Kaohsiung Medical University - Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Siriraj Hospital
🇹🇭Bangkok, Thailand
Pamukkale University
🇹🇷Denizli, Turkey
Complejo Hospitalario de Navarra - H. de Navarra, Hematología C/ de Irunlarrea, 3, Pamplona
🇪🇸Pamplona, Spain
National Taiwan University Hospital
🇨🇳Taipei City, Taipei, Taiwan
Thammasat University Hospital
🇹🇭Khlong Luang, Thailand
Ondokuz Mayis University Medical Faculty - Hematology
🇹🇷Samsun, Turkey
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Ramathibodi Hospital - Mahidol University - Hematology
🇹🇭Bangkok, Thailand
Inonu University Turgut Ozal Medical Center
🇹🇷Malatya, Turkey
NHS Greater Glasgow and Clyde
🇬🇧Glasgow, United Kingdom
The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
University of Southern California Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The Kirklin Clinic of UAB Hospital
🇺🇸Birmingham, Alabama, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Fiona Stanley Hosital
🇦🇺Murdoch, Western Australia, Australia
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
A.O. San Gerardo di Monza - L'Ospedale San Gerardo di Monza e l'Università di Milano
🇮🇹Monza, Lombardia, Italy
Azienda Ospedaliero Universitaria Policlinico - Vittorio Emanuele
🇮🇹Catania, Italy
AOU Careggi
🇮🇹Firenze, Italy
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST IRCCS
🇮🇹Meldola, Italy
Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
🇮🇹Milano, Italy
AOU Maggiore della Carità
🇮🇹Novara, Italy
Arcispedale S. Maria Nuova, AO di Reggio Emilia
🇮🇹Reggio Emilia, Italy
A.O. Citta della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Sakarya Research and Training Hospital
🇹🇷Adapazarı, Turkey
Ankara University Faculty of Medicine
🇹🇷Ankara, Turkey
Gazi University Medical Faculty
🇹🇷Ankara, Turkey
Gaziantep University Faculty of Medicine
🇹🇷Gaziantep, Turkey
Mersin University Medical Faculty
🇹🇷Mersin, Turkey
Centre Hospitalier Regional Universitaire Brest Hopital Morvan
🇫🇷Brest Cedex, France
Institut Universitaire du Cancer de Toulouse Oncopole
🇫🇷Toulouse, France
Centre Hospitalier Le Mans
🇫🇷Le Mans, France
Hopital Paul Brousse - Aphp Hôpitaux Universitaires Paris Su
🇫🇷Villejuif, France
Guy's and Saint Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, United Kingdom
Instituto de Ensino e Pesquisa São Lucas
🇧🇷Sao Paulo, Brazil
Associação Educadora São Carlos AESC - Hospital Mãe de Deus - Centro de Pesquisa
🇧🇷Porto Alegre, Brazil
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
UKE - Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Technische Universität Dresden
🇩🇪Dresden, Sachsen, Germany
Hospital San Pedro de Alcantara
🇪🇸Cáceres, Spain
Hospital Universitario Son Espases
🇪🇸Palma de Mallorca, Spain
Hospital Universitario Doctor Peset
🇪🇸Valencia, Spain
H. Quirón Zaragoza
🇪🇸Zaragoza, Spain
Carmel MC
🇮🇱Haifa, Israel
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Universitätsklinikum Jena
🇩🇪Jena, Thuringen, Germany
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Stanford Cancer Center - Palo Alto
🇺🇸Stanford, California, United States
University Cancer Institute
🇺🇸Boynton Beach, Florida, United States
Mt. Sinai
🇺🇸New York, New York, United States
Brookdale University Hospital and Medical Center
🇺🇸Brooklyn, New York, United States
New York Presbyterian/Weill Cornell Medical Center
🇺🇸New York, New York, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Medical College of Wisconsin - Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
Instituto Medico Alexander Fleming
🇦🇷Buenos Aires, Argentina
Hospital das Clínicas da Universidade de São Paulo
🇧🇷Sao Paulo, Brazil
Hospital Privado - Centro Medico de Cordoba - Oncology
🇦🇷Córdoba, Argentina
Hospital Erasto Gaertner
🇧🇷Curitiba, Parana, Brazil
The Alfred Hospital
🇦🇺Melbourne, Australia
Hospital A C Camargo - Fundacao Antonio Prudente
🇧🇷Sao Paulo, Brazil
Instituto D'or de Pesquisa e Ensino
🇧🇷São Paulo, Brazil
Instituto COI São Paulo
🇧🇷São Paulo, Brazil
University Multiprofile Hospital for Active Treatment Sveti Georgi, Plovdiv
🇧🇬Plovdiv, Bulgaria
Military Medical Academy, Multiprofile for active treatment, Sofia
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment Saint Ivan Rilski, Sofia
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment Alexandrovska, Sofia
🇧🇬Sofia, Bulgaria
Center Hospitalier Universitaire d'Angers
🇫🇷Angers, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, France
Universitaetsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Somogy Megyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Somogy, Hungary
Ha'Emek Medical Center
🇮🇱Afula, Israel
Assuta Ashdod University Hospital
🇮🇱Ashdod, Israel
Assuta MC
🇮🇱Tel Aviv, Israel
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Azienda Ospedaliera Ospedali Riuniti Marche Nord - Pesaro
🇮🇹Pesaro, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
General Hospital Sibenik
🇭🇷Sibenik, Croatia
KB Sestre Milosrdnice
🇭🇷Zagreb, Croatia