Primary Myelofibrosis (PMF)Phase 2/3BOREASNCT03662126
KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment
A Phase 2/3 study testing KRT-232 and Best Available Therapy (BAT) in people with Primary Myelofibrosis (PMF) and Post-Polycythemia Vera MF (Post-PV-MF), run by Kartos Therapeutics, Inc. at 191 sites in 28 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF)
- What is being tested?
- KRT-232 and Best Available Therapy (BAT)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 385 participants
- Where
- 191 sitesin 28 countries
- Study dates
- 15 Jan 2019to 31 Dec 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
191 sites in 28 countries.
191 sites in 28 countries
United States19 sites, 9 recruiting
- Active, not recruiting
The Kirklin Clinic of UAB Hospital
Birmingham, Alabama, 35294
- Withdrawn
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
- Withdrawn
University Cancer Institute
Boynton Beach, Florida, 33426
- Recruiting
Brookdale University Hospital and Medical Center
Brooklyn, New York, 11212
- Recruiting
Gabrail Cancer Center
Canton, Ohio, 44718
- Completed
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
- Recruiting
University of Illinois at Chicago
Chicago, Illinois, 60612
- Completed
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
- Active, not recruiting
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, 90033
- Recruiting
Medical College of Wisconsin - Froedtert Hospital
Milwaukee, Wisconsin, 53226
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37203
- Withdrawn
New York Presbyterian/Weill Cornell Medical Center
New York, New York, 10021
- Recruiting
Mt. Sinai
New York, New York, 10029
- Completed
Oregon Health and Science University
Portland, Oregon, 97239
- Recruiting
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
- Active, not recruiting
Stanford Cancer Center - Palo Alto
Stanford, California, 94305
- Completed
Innovative Clinical Research Institute
Whittier, California, 90603
Italy15 sites, 15 recruiting
- Recruiting
PO Civile SS.Antonio e Biagio
Alessandria, 15121
- Recruiting
AOU Ospedali Riuniti Umberto I G.M. Lancisi G. Salesi
Ancona, 60123
- Recruiting
A.O.di Bologna Policl.S.Orsola
Bologna, 41038
- Recruiting
AO Spedali Civili di Brescia
Brescia, 25123
- Recruiting
Azienda Ospedaliero Universitaria Policlinico - Vittorio Emanuele
Catania, 95123
- Recruiting
AOU Careggi
Florence, 50141
- Recruiting
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST IRCCS
Meldola
- Recruiting
Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
Milan, 20122
- Recruiting
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162
- Recruiting
A.O. San Gerardo di Monza - L'Ospedale San Gerardo di Monza e l'Università di Milano
Monza, Lombardy, 20900
- Recruiting
AOU Maggiore della Carità
Novara, 28100
- Recruiting
Azienda Ospedaliera Ospedali Riuniti Marche Nord - Pesaro
Pesaro, 61121
- Recruiting
Arcispedale S. Maria Nuova, AO di Reggio Emilia
Reggio Emilia, 42123
- Recruiting
Policlinico Universitario Agostino Gemelli
Roma, 00168
- Recruiting
A.O. Citta della Salute e della Scienza di Torino
Torino, 10126
Brazil12 sites, 12 recruiting
- Recruiting
UNICAMP - Universidade Estadual de Campinas Hemocentro
Campinas, São Paulo, 13083
- Recruiting
Hospital Erasto Gaertner
Curitiba, Paraná, 81520
- Recruiting
Centro de oncologia Leonardo da Vinci
Fortaleza, Ceará, 60140-025
- Recruiting
Hospital das Clínicas UFG
Goiânia, 74605
- Recruiting
Fundacao Doutor Amaral Carvalho
Jaú, 17210-120
- Recruiting
Hospital de Clinicas de Porto Alegre - Centro de Pesquisa Clinica
Porto Alegre, 90035-903
- Recruiting
Associação Educadora São Carlos AESC - Hospital Mãe de Deus - Centro de Pesquisa
Porto Alegre, 90880-480
- Recruiting
Instituto de Ensino e Pesquisa São Lucas
São Paulo, 01236-030
- Recruiting
Hospital A C Camargo - Fundacao Antonio Prudente
São Paulo, 01509-900
- Recruiting
Instituto D'or de Pesquisa e Ensino
São Paulo, 04502-001
- Recruiting
Hospital das Clínicas da Universidade de São Paulo
São Paulo, 05403-000
- Recruiting
Instituto COI São Paulo
São Paulo, 1321001
Germany12 sites, 10 recruiting
- Active, not recruiting
Universitätsklinikum Aachen
Aachen, North Rhine-Westphalia, 52074
- Recruiting
Charité Universitätsmedizin Berlin
Berlin, 13353
- Recruiting
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
Dresden, Saxony, 01307
- Recruiting
Technische Universität Dresden
Dresden, Saxony, 01307
- Recruiting
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45147
- Recruiting
Universitätsklinikum Halle
Halle, Saxony-Anhalt, 06120
- Recruiting
UKE - Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20251
- Recruiting
Universitätsklinikum Jena
Jena, Thuringia, 07747
- Active, not recruiting
Universitätsmedizin der Johannes Gutenberg Universität Mainz
Mainz
- Recruiting
Klinikum Rechts der Isar der Technischen Universität München Apotheke
München, Bavaria, 81675
- Recruiting
Stauferklinikum Schwäbisch Gmünd
Mutlangen, 73557
- Recruiting
Praxis für Hämatologie und Onkologie
Saarbrücken, 66113
Spain12 sites, 11 recruiting
- Recruiting
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
- Recruiting
Hospital Universitario Vall d'Hebrón
Barcelona, 08035
- Recruiting
Hospital de La Santa Creu i Sant Pau
Barcelona, 8041
- Recruiting
Hospital San Pedro de Alcantara
Cáceres, 1003
- Recruiting
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, Las Palmas, 35010
- Active, not recruiting
Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, Madrid, 28222
- Recruiting
Hospital Universitario Virgen de la Victoria
Málaga, 29010
- Recruiting
Hospital Universitario Son Espases
Palma de Mallorca, 07120
- Recruiting
Complejo Hospitalario de Navarra - H. de Navarra, Hematología C/ de Irunlarrea, 3, Pamplona
Pamplona, 31008
- Recruiting
Hospital Universitario de Salamanca
Salamanca, 37007
- Recruiting
Hospital Universitario Doctor Peset
Valencia, 46017
- Recruiting
H. Quirón Zaragoza
Zaragoza, 50012
France11 sites, 9 recruiting
- Recruiting
Centre Hospitalier Universitaire D'Amiens (Hopital Sud) - Hématologie Clinique
Amiens, 80054
- Recruiting
Center Hospitalier Universitaire d'Angers
Angers, 49933 Cedex 09
- Recruiting
C.H de la Côte Basque - Serviv
Bayonne, 64100
- Recruiting
Centre Hospitalier Regional Universitaire Brest Hopital Morvan
Brest, 29609
- Active, not recruiting
Centre Hospitalier Universitaire of Caen Normandie - Côte de Nacre
Caen, 14000
- Recruiting
Centre Hospitalier Le Mans
Le Mans
- Active, not recruiting
Centre Hospitalier Universitaire de Nîmes
Nîmes, 30029 Cedex 9
- Recruiting
Hôpital Saint-Louis
Paris, 75010
- Recruiting
Centre Hospitalier Universitaire de Poitiers
Poitiers
- Recruiting
Institut Universitaire du Cancer de Toulouse Oncopole
Toulouse, 31059
- Recruiting
Hopital Paul Brousse - Aphp Hôpitaux Universitaires Paris Su
Villejuif, 94800
Israel11 sites, 11 recruiting
- Recruiting
Ha'Emek Medical Center
Afula, 1834111
- Recruiting
Assuta Ashdod University Hospital
Ashdod
- Recruiting
Rambam Medical Centre
Haifa, 31096
- Recruiting
Carmel MC
Haifa
- Recruiting
Hadassah Medical Organisation
Jerusalem, 91120
- Recruiting
Hematology Institute
Kfar Saba, 44281
- Recruiting
Western Galilee Hospital - Nahariya
Nahariya, 22100
- Recruiting
Rabin Medical Center - Beilinson Hospital
Petah Tikva, 49100
- Recruiting
Tel Aviv Sourasky Medical Center - Oncology
Tel Aviv, 6423906
- Recruiting
Assuta MC
Tel Aviv, 64239
- Recruiting
Assaf Harofeh Medical Center - Hematology
Ẕerifin, 7030000
Romania10 sites, 10 recruiting
- Recruiting
Cen Med de Diagn si Trat Amb NEOMED
Brasov, 500283
- Recruiting
Spitalul Clinic Colentina
Bucharest, 020125
- Recruiting
Spitalul Clinic Coltea
Bucharest, 030171
- Recruiting
Medicover
Bucharest, 060201
- Recruiting
Institutul Oncologic "Prof. Dr. Ion Chiricuta"
Cluj-Napoca, 400015
- Recruiting
Spitalul Clinic Municipal Filantropia Craiova
Craiova, 200143
- Recruiting
Institutul Regional de Oncologie Iasi
Iași, 700483
- Recruiting
Spitalul Clinic Judetean de Urgenta Tg Mures
Târgu Mureş, 540136
- Recruiting
Spitalul Clinic Municipal de Urgenta Timisoara
Timișoara, 300079
- Recruiting
Oncomed
Timișoara, 300329
Poland9 sites, 6 recruiting
- Active, not recruiting
Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
Brzozów, Podkarpackie Voivodeship, 36-200
- Recruiting
Szpital Uniwersytecki nr 2 im dr. Jana Biziela
Bydgoszcz, 86-168
- Recruiting
Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
Chorzów, Silesian Voivodeship, 41-500
- Withdrawn
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin, 20-081
- Recruiting
SPZOZ MSWiA z Warminsko - Mazurskim Centrum Onkologii
Olsztyn
- Recruiting
Szpital Wojewódzki w Opolu
Opole, 45-061
- Withdrawn
Clinical Research Center Spółka z Ograniczoną Odpowiedzialnością Medic-R sp. k.
Poznan, 60-848
- Recruiting
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
Słupsk, 76-200
- Recruiting
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
Wroclaw, Lower Silesian Voivodeship, 53-439
South Korea8 sites, 8 recruiting
- Recruiting
Inje University Busan Paik Hospital
Busan, 47392
- Recruiting
Kyungpook National University Hospital
Daegu, 41944
- Recruiting
Yeungnam University Medical Center
Daegu, 42415
- Recruiting
Keimyung University Dongsan Medical Center
Daegu, 42601
- Recruiting
CHA Bundang Medical Center, CHA University
Seongnam-si, Seongnam-si
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Samsung Medical Center
Seoul, 06351
- Recruiting
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 6591
Turkey (Türkiye)8 sites, 8 recruiting
- Recruiting
Sakarya Research and Training Hospital
Adapazarı, 54100
- Recruiting
Ankara University Faculty of Medicine
Ankara, 06500
- Recruiting
Gazi University Medical Faculty
Ankara, 06500
- Recruiting
Pamukkale University
Denizli, 20160
- Recruiting
Gaziantep University Faculty of Medicine
Gaziantep, 27100
- Recruiting
Inonu University Turgut Ozal Medical Center
Malatya, 44280
- Recruiting
Mersin University Medical Faculty
Mersin, 33110
- Recruiting
Ondokuz Mayis University Medical Faculty - Hematology
Samsun, 55280
Bulgaria7 sites, 6 recruiting
- Recruiting
University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven
Pleven
- Recruiting
University Multiprofile Hospital for Active Treatment Sveti Georgi, Plovdiv
Plovdiv
- Recruiting
Military Medical Academy, Multiprofile for active treatment, Sofia
Sofia, 1606
- Recruiting
Acibadem City Clinic Tokuda Hospital, Sofia
Sofia
- Recruiting
Specialized Hospital for Active Therapy of Hematological Disorders
Sofia
- Withdrawn
University Multiprofile Hospital for Active Treatment Alexandrovska, Sofia
Sofia
- Recruiting
University Multiprofile Hospital for Active Treatment Saint Ivan Rilski, Sofia
Sofia
Hungary7 sites, 4 recruiting
- Withdrawn
Semmelweis Egyetem
Budapest, 1083
- Recruiting
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
Budapest
- Completed
Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
Debrecen, 4032
- Withdrawn
Somogy Megyei Kaposi Mór Oktató Kórház
Kaposvár, Somogy County, 7400
- Recruiting
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400
- Recruiting
Szegedi Tudományegyetem
Szeged, 6725
- Recruiting
Markusovszky Egyetemi Oktatókórház
Szombathely, Vas County, H-9700
Australia6 sites, 6 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide
- Recruiting
Monash Medical Centre
Clayton, Victoria, 3168
- Recruiting
The Alfred Hospital
Melbourne
- Recruiting
Fiona Stanley Hosital
Murdoch, Western Australia, 6150
- Recruiting
South Eastern Private Hospital
Noble Park, 3174
- Recruiting
Icon Cancer Center
South Brisbane
Portugal5 sites, 5 recruiting
- Recruiting
H. Infante Dom Pedro. Centro Hospitalar do Baixo Vouga
Aveiro, 3814-501
- Recruiting
Hospital de Braga
Braga, 4710-243
- Recruiting
Instituto Português de Oncologia de Coimbra
Coimbra, 3000-075
- Recruiting
Champalimaud Cancer Center
Lisbon, 1400-038
- Recruiting
H. São Francisco Xavier-Centro Hospitalar Lisboa Ocidental
Lisbon, 1495-005
Thailand5 sites, 5 recruiting
- Recruiting
Ramathibodi Hospital - Mahidol University - Hematology
Bangkok, 10400
- Recruiting
Siriraj Hospital
Bangkok, 10700
- Recruiting
Thammasat University Hospital
Khlong Luang, 12120
- Recruiting
Srinagarind Hospital (KhonKaen University)
Khon Kaen, 40002
- Recruiting
Songklanagarind Hospital
Songkhla, 90110
Argentina4 sites, 4 recruiting
- Recruiting
Instituto Medico Alexander Fleming
Buenos Aires
- Recruiting
Centro Medico San Luis
CABA, 1425
- Recruiting
Hospital Privado - Centro Medico de Cordoba - Oncology
Córdoba, X5016KEH
- Recruiting
Sanatorio de la Mujer
Rosario, Santa Fe Province, S2000ORE
Mexico4 sites, 4 recruiting
- Recruiting
Universidad Autonoma de Nuevo Leon (UANL) - Hospital Universitario "Dr. Jose Eleuterio Gonzalez
Monterrey, Nuevo León, 64460
- Recruiting
Instituto Mexicano del Seguro Social
Monterrey, 64180
- Recruiting
Oaxaca Site Management Organization OSMO
Oaxaca City, 6800
- Recruiting
Sociedad de Metabolismo y Corazón S.C. - Oncology
Veracruz, 91910
Taiwan4 sites, 4 recruiting
- Recruiting
Chang Gung Medical Foundation - ChiaYi Chang Gung Memorial Hospital - Chiayi Branch
Chiayi City
- Recruiting
Kaohsiung Medical University - Chung-Ho Memorial Hospital
Kaohsiung City, 807
- Recruiting
China Medical University Hospital
Taichung, 40447
- Recruiting
National Taiwan University Hospital
Taipei City, Taipei, 100
United Kingdom4 sites
- Active, not recruiting
University Hospitals Birmingham NHS Foundation Trust
Birmingham
- Active, not recruiting
NHS Greater Glasgow and Clyde
Glasgow
- Active, not recruiting
Guy's and Saint Thomas' NHS Foundation Trust
London, SE1 9RT
- Active, not recruiting
Oxford University Hospitals NHS Foundation Trust
Oxford
Croatia3 sites, 3 recruiting
- Recruiting
General Hospital Sibenik
Šibenik, 22000
- Recruiting
Clinical Hospital Centre Osijek
Zagreb, 10000
- Recruiting
KB Sestre Milosrdnice
Zagreb, 10000
Czechia3 sites, 2 recruiting
- Recruiting
FN Hradec Kralove
Králová, 500 05
- Recruiting
Vseonecma fakultni nemocrince V Praze
New Town
- Withdrawn
Fakultní Nemocnice Olomouc
Olomouc, 779 00
Greece3 sites, 3 recruiting
- Recruiting
University General Hospital of Ioannina
Ioannina, Ioannina, 45500
- Recruiting
University Campus of Patras - Hematology
Pátrai, 26504
- Recruiting
AHEPA General Hospital of Thessaloniki
Thessaloniki, 54636
Russia3 sites
- Withdrawn
Clinical oncological dispensary
Omsk, 644013
- Withdrawn
Saint-Petersburg SMU I.P.Pavlov
Saint Petersburg, 197089
- Withdrawn
Oncologic dispensary of Komi Republic
Syktyvkar, 167904
Hong Kong2 sites, 2 recruiting
- Recruiting
Queen Mary Hospital
Hong Kong, 150001
- Recruiting
Prince of Wales Hospital - Medicine
Shatin
Philippines2 sites, 2 recruiting
- Recruiting
Perpetual Succour Hospital - Hemat/Transfusion Med
Cebu City, 6000
- Recruiting
University of the Philippines - Philippine General Hospital
Manila, 1000
Canada1 site
- Active, not recruiting
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9
Lithuania1 site, 1 recruiting
- Recruiting
Hospital of Lithuanian University of Health Sciences Kaunas
Kaunas, LT-50161
About this study
Official title: 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.
- Conditions
- Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF)
- Being tested
- KRT-232, Best Available Therapy (BAT)
- Keywords
- navtemadlin
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRT-232Drug
KRT-232, administered by mouth
Best Available Therapy (BAT)Drug
Best available therapy options include:
- hydroxyurea
- chemotherapy or
- supportive care (including but not limited to corticosteroids and androgens; JAK inhibitors not allowed).
| Study group | Role | What they receive |
|---|---|---|
| Part A Cohort 1 | Experimental | KRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) Receives: Drug: KRT-232 |
| Part A Cohort 2 | Experimental | KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) Receives: Drug: KRT-232 |
| Part A Cohort 3 | Experimental | KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) Receives: Drug: KRT-232 |
| Part A Cohort 4b | Experimental | KRT-232 240 mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles) Receives: Drug: KRT-232 |
| Part B Arm 1 KRT-232 | Experimental | KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) Receives: Drug: KRT-232 |
| Part B Arm 2 Best Available Therapy | Active comparator | Best available therapy at the discretion of the investigator, on a 28-day cycle. Receives: Drug: Best Available Therapy (BAT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
(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
Measured: 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)
Measured: 24 Weeks
Secondary outcomes (7)
(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
Measured: 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
Measured: 24 Weeks
(Part B only) Overall Survival (OS)
Time from randomization to death from any cause
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2018
- Study start15 Jan 2019
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Myelofibrosis (PMF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 385 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kartos Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03662126
- Sponsor's protocol ID
- KRT-232-101
- Acronym
- BOREAS
- Status last verified
- Apr 2023
- First submitted
- 5 Sep 2018
- Last updated
- 28 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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 at a glance
From the registry record, last updated by the sponsor on 28 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03662126
- Acronym / sponsor ID
- BOREAS / KRT-232-101
- Conditions
- Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF)
- Keywords
- navtemadlin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 385 participants (estimated)
- Lead sponsor
- Kartos Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Jan 2019 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 7 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part A Cohort 1 | Experimental | Drug: KRT-232KRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) |
| Part A Cohort 2 | Experimental | Drug: KRT-232KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) |
| Part A Cohort 3 | Experimental | Drug: KRT-232KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) |
| Part A Cohort 4b | Experimental | Drug: KRT-232KRT-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 | Experimental | Drug: KRT-232KRT-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 comparator | Drug: Best Available Therapy (BAT)Best available therapy at the discretion of the investigator, on a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KRT-232KRT-232, administered by mouth | Drug | Part A Cohort 1, Part A Cohort 2, Part A Cohort 3, Part A Cohort 4b, Part B Arm 1 KRT-232 |
| Best Available Therapy (BAT)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). | Drug | Part B Arm 2 Best Available Therapy |
Primary outcome
(Part A Only) Spleen Volume Reduction (SVR)
Time frame: 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)
Time frame: 24 Weeks
The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan (central review)
7 secondary outcomes
(Part A only) Improvement in Total Symptom Score (TSS)
Time frame: 48 weeks
(Part B only) Improvement of Total Symptom Score (TSS)
Time frame: 24 Weeks
(Part B only) Overall Survival (OS)
Time frame: 48 months
(Part B only) Progression free survival (PFS)
Time frame: 48 months
(Part B Only) Overall Spleen Volume Reduction (SVR)
Time frame: 48 months
(Part B Only) Spleen Response Duration
Time frame: 48 months
(Part B Only) Rate of conversion from RBC transfusion dependent to independent
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2023.
- BackgroundAl-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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
191 sites in 28 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing KRT-232 and Best Available Therapy (BAT) in people with Primary Myelofibrosis (PMF) and Post-Polycythemia Vera MF (Post-PV-MF), run by Kartos Therapeutics, Inc. at 191 sites in 28 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 191 sites in United States, Italy, Brazil, Germany, Spain and 23 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact John Mei (650-542-0136, jmei@kartosthera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
(Part A Only) Spleen Volume Reduction (SVR) (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03662126, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2023.