An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib
Study Purpose
A Phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of fedratinib compared to best available therapy (BAT) in subjects with DIPSS (Dynamic International Prognostic Scoring System)-intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF) and previously treated with ruxolitinib. The primary objective of the study is to evaluate the percentage of subjects with at least 35% spleen volume reduction in the fedratinib and the BAT arms.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years and Over |
Gender | All |
Inclusion Criteria:
1. Subject is at least 18 years of age at the time of signing the informed consent form (ICF) 2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0, 1 or 2. 3. Subject has diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-ET or post-PV myelofibrosis according to the IWG-MRT 2007 criteria, confirmed by the most recent local pathology report. 4. Subject has a DIPSS Risk score of Intermediate-2 or High. 5. Subject has a measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥ 450 cm3 by MRI or CT-scan and by palpable spleen measuring ≥ 5 cm below the left costal margin. 6. Subject has a measurable total symptoms score (≥ 1) as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) 7. Subject has been previously exposed to ruxolitinib, and must meet at least one of the following criteria (a and/or b) 1. Treatment with ruxolitinib for ≥ 3 months with inadequate efficacy response (refractory) defined as < 10% spleen volume reduction by MRI or < 30% decrease from baseline in spleen size by palpation or regrowth (relapsed) to these parameters following an initial response. 2. Treatment with ruxolitinib for ≥ 28 days complicated by any of the following (intolerant):- - Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months) or.
- - Grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while on treatment with ruxolitinib.
Exclusion Criteria:
1. Any of the following laboratory abnormalities: 1. Platelets < 50 x 109/L. 2. Absolute neutrophil count (ANC) < 1.0 x 109/L. 3. White blood count (WBC) > 100 x 109/L. 4. Myeloblasts ≥ 5 % in peripheral blood. 5. Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (as per the Modification of Diet in Renal Disease [MDRD] formula) 6. Serum amylase or lipase > 1.5 x upper limit of normal (ULN) 7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN) 8. Total bilirubin > 1.5 x ULN, subject's total bilirubin between 1.5- - 3.0 x ULN are eligible if the direct bilirubin fraction is < 25% of the total bilirubin.
Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT03952039 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Celgene |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Bristol-Myers Squibb |
Principal Investigator Affiliation | Bristol-Myers Squibb |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
Overall Status | Recruiting |
Countries | Australia, Austria, Belgium, China, Czechia, France, Germany, Hungary, Ireland, Italy, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, United Kingdom |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Primary Myelofibrosis, Post-Polycythemia Vera, Myelofibrosis |
Study Website: | View Trial Website |
This Phase 3, multicenter, randomized, two-arm, open-label study will include subjects with intermediate or high-risk (as per the DIPSS score) primary myelofibrosis (PMF), postpolycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF). This study will be conducted in compliance with International Council for Harmonisation (ICH) Good Clinical Practices (GCPs). Study design includes:
- - A 28-day Screening Period.
- - 2:1 Randomization to fedratinib or best available therapy (BAT) - Stratification at Randomization according to: - Spleen size by palpation: < 15 cm below left costal margin (LCM) versus ≥ 15 cm below LCM.
- - Platelets ≥ 50 to < 100 x 109/L versus platelets ≥ 100 x 109/L.
- - Refractory or relapsed to ruxolitinib treatment versus intolerant to ruxolitinib treatment.
- - Study Treatment Period (time on study drug plus 30 days after last dose) - Subjects are allowed to crossover from BAT to the fedratinib arm after the Cycle 6 response assessment or before the Cycle 6 response assessment in the event of a confirmed progression of splenomegaly by MRI/CT scan.
Arms
Experimental: Fedratinib 400mg/day
Will include up to 128 subjects receiving fedratinib 400 mg self-administered Investigational Product (IP) on an outpatient basis, once daily preferably together with food during an evening meal at the same time each day in consecutive 4-week (28-day) cycles.
Active Comparator: Best Available Therapy (BAT)
Best-available Investigator-selected therapy included a number of available compounds to treat MF and/or its symptoms and was chosen by the investigator for each subject. Therapy changed at different times during the treatment period. No investigational agents (e.g. not approved for the treatment of any indication) were allowed. BAT also included the choice of no treatment.
Interventions
Drug: - FEDRATINIB
A potent and selective inhibitor of JAK2 kinase activity
Drug: - Best Available Therapy (BAT)
Best available therapy (BAT)
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
International Sites
Status
Completed
Address
Local Institution - 103
Darlinghurst, New South Wales, 2010
Status
Recruiting
Address
Saint Vincent's Hospital
Darlinghurst, New South Wales, 2010
Status
Recruiting
Address
Local Institution - 101
Adelaide, South Australia, 5000
Status
Recruiting
Address
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Status
Recruiting
Address
Peninsula Private Hospital
Frankston, Victoria, 3199
Status
Recruiting
Address
Eastern Health Clinical School
Box Hill, , 3128
Status
Recruiting
Address
Alfred Hospital
Melbourne, , 3004
Status
Recruiting
Address
Medical University of Graz
Graz, , A-8036
Status
Completed
Address
Local Institution - 154
Innsbruck, , 6020
Status
Recruiting
Address
Medical University Innsbruck
Innsbruck, , 6020
Status
Recruiting
Address
Elisabethinen Hospital Linz
Linz, , 4020
Status
Completed
Address
Local Institution - 151
Salzburg, , 5020
Status
Recruiting
Address
Salzburger Landkliniken St. Johanns-Spital
Salzburg, , 5020
Status
Recruiting
Address
Medical University of Vienna
Vienna, , 1090
Status
Recruiting
Address
Klinikum Wels-Grieskirchen GmbH
Wels, , 4600
Status
Completed
Address
Local Institution - 153
Wels, , 4600
Status
Recruiting
Address
Hanusch Krankenhaus
Wien, , 1140
Status
Recruiting
Address
AZ Sint-Jan AV Brugge
Brugge, , 8000
Status
Recruiting
Address
Cliniques Universitaires Saint-Luc
Bruxelles, , 1200
Status
Completed
Address
Local Institution - 202
Bruxelles, , 1200
Status
Recruiting
Address
Centre Hospitalier de Jolimont-Lobbes
La Louvière-(Haine St-Paul), , 7100
Status
Recruiting
Address
Local Institution - 205
La Louvière-(Haine St-Paul), , 7100
Status
Recruiting
Address
UZ Leuven
Leuven, , 3000
Status
Recruiting
Address
Centre Hospitalier Universitaire de Liege - Sart Tilman
Liege, , 4000
Status
Recruiting
Address
Cliniques Universitaires UCL de Mont-Godine
Yvoir, , 5530
Status
Not yet recruiting
Address
Peking University People's Hospital
Beijing, , 100044
Status
Not yet recruiting
Address
Fujian Medical University Union Hospital
Fuzhou, , 350001
Status
Recruiting
Address
Guangdong General Hospital
Guangzhou, Guangdong, , 510080
Status
Not yet recruiting
Address
Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University
Nanjing, , 210029
Status
Recruiting
Address
Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, , 300041
Status
Recruiting
Address
Local Institution - 553
Tianjin, , 300041
Status
Recruiting
Address
Local Institution - 557
Zhengzhou, , 0
Status
Not yet recruiting
Address
Henan Cancer Hospital
Zhengzhou, ,
Status
Recruiting
Address
Fakultni Nemocnice Brno
Brno, , 625 00
Status
Completed
Address
Local Institution - 700
Brno, , 625 00
Status
Recruiting
Address
Fakultni Nemocnice Ostrava
Ostrava-Poruba, , 708 52
Status
Completed
Address
Local Institution - 701
Prague 2, , 128 08
Status
Recruiting
Address
Vseobecna Fakultni Nemocnice v Praze
Prague 2, , 128 08
Status
Recruiting
Address
CHU d'Angers
Angers, , 49033
Status
Active, not recruiting
Address
Local Institution - 255
Angers, , 49033
Status
Recruiting
Address
CHRU de Brest - Hopital Morvan
Brest, , 29200
Status
Recruiting
Address
Centre Hospitalier de Lens
Lens Cedex, , 62307
Status
Completed
Address
CHRU Claude Huriez
Lille, , 59037
Status
Recruiting
Address
CHU Nice Hopital de L'Archet 2
Nice Cedex 3, , 06200
Status
Recruiting
Address
Centre Hospitalier Universitaire de Nimes - Hopital Universitaire Caremeau
Nimes Cedex 9, , 30029
Status
Recruiting
Address
Hopital Saint Louis
Paris, , 75010
Status
Active, not recruiting
Address
Local Institution - 252
Paris, , 75010
Status
Recruiting
Address
CHRU - Hopital du Haut Leveque
Pessac, , 33604
Status
Recruiting
Address
Centre Hospitalier Lyon Sud - Hospices Civils de Lyon Groupement Hospitalier Sud
Pierre-Benite, , 69495
Status
Recruiting
Address
CHU La Miletrie
Poitiers Cedex, , 86021
Status
Recruiting
Address
CHU Strasbourg - Hopital Civil
Strasbourg, , 67091
Status
Recruiting
Address
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse Cedex 9, , 31059
Status
Completed
Address
Local Institution - 302
Aachen, , 52074
Status
Recruiting
Address
Unviversitatsklinikum Aachen
Aachen, , 52074
Status
Recruiting
Address
Klinikum der Johann Wolfgang Goethe Universitat
Frankfurt am Main, , 60590
Status
Recruiting
Address
Universitaetsklinikum Halle Saale
Halle, , 06120
Status
Recruiting
Address
Universitaetsklinikum Jena
Jena, , 07747
Status
Completed
Address
Local Institution - 307
Magdeburg, , 39120
Status
Recruiting
Address
Universitaetsklinikum Magdeburg A oeR
Magdeburg, , 39120
Status
Recruiting
Address
University of Heidelberg - Universitatsklinikum Mannheim
Mannheim, , 68167
Status
Recruiting
Address
Johannes Wiesling Klinikum Minden
Minden, , 32429
Status
Completed
Address
Local Institution - 305
Ulm, , 89081
Status
Recruiting
Address
Universitaetsklinikum Ulm
Ulm, , 89081
Status
Recruiting
Address
Semmelweis Egyetem
Budapest, , 1088
Status
Recruiting
Address
Local Institution - 601
Gyor, , 9023
Status
Recruiting
Address
Petz Aladar Megyei Oktato Korhaz
Gyor, , 9023
Status
Recruiting
Address
Local Institution - 602
Kaposvar, , 7400
Status
Recruiting
Address
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvar, , 7400
Status
Recruiting
Address
SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
Nyiregyhaza, , 4400
Status
Recruiting
Address
Local Institution - 603
Szeged, , 6720
Status
Recruiting
Address
Szegedi Tudomanyegyetem - Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, , 6720
Status
Recruiting
Address
Cork University Hospital
Cork, ,
Status
Recruiting
Address
Mater Misericordiae University Hospital
Dublin, , Dublin 7
Status
Recruiting
Address
St. James' Hospital
Dublin, , Dublin 8
Status
Recruiting
Address
A.O.U. di Bologna Policlinico S.Orsola-Malpighi
Bologna, , 40138
Status
Recruiting
Address
ASST Spedali Civili P.O. di Brescia
Brescia, , 25123
Status
Recruiting
Address
Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele - Ospedale Gaspare Rodolico
Catania, , 95123
Status
Recruiting
Address
Azienda Ospedaliero-Universitaria Careggi
Firenze, , 50134
Status
Recruiting
Address
IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
Milano, , 20122
Status
Recruiting
Address
Local Institution - 358
Milano, , 20122
Status
Completed
Address
Local Institution - 362
Naples, , 80131
Status
Recruiting
Address
Ospedale Cardarelli
Naples, , 80131
Status
Recruiting
Address
Fondazione IRCCS Policlinico San Matteo
Pavia, , 27100
Status
Completed
Address
Local Institution - 357
Pavia, , 27100
Status
Recruiting
Address
Policlinico Umberto I - Universita La Sapienza
Roma, , 00168
Status
Recruiting
Address
Universita Cattololica del Sacro Cuore
Roma, , 00168
Status
Recruiting
Address
Azienda Ospedaliera S. Andrea - Università La Sapienza
Roma, , 00189
Status
Recruiting
Address
Local Institution - 359
Roma, , 00189
Status
Recruiting
Address
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino, , 10126
Status
Recruiting
Address
Local Institution - 355
Torino, , 10126
Status
Recruiting
Address
Azienda Ospedaliero-Universitaria Santa Maria della Misericordia die Udine
Udine, , 33100
Status
Recruiting
Address
Local Institution - 352
Varese, , 21100
Status
Recruiting
Address
Universita degli Studi dell'Insubria - Ospedale di Circolo e Fondazione Macchi - Varese
Varese, , 21100
Status
Recruiting
Address
Azienda Ospedaliera Universitaria Integrata di Verona
Verona, , 37134
Status
Recruiting
Address
Local Institution - 364
Verona, , 37134
Status
Recruiting
Address
Local Institution - 900
Seongnam-si, , 13620
Status
Recruiting
Address
Seoul National University Bundang Hospital
Seongnam-si, , 13620
Status
Completed
Address
Local Institution - 905
Seoul, , 06351
Status
Recruiting
Address
Samsung Medical Center
Seoul, , 06351
Status
Recruiting
Address
Seoul St Marys Hospital College of Medicine The Catholic University of Korea
Seoul, , 137-701
Status
Recruiting
Address
Soon Chun Hyang University Hospital Seoul
Seoul, , 140-887
Status
Recruiting
Address
Seoul National University Hospital
Seoul, , 3080
Status
Recruiting
Address
Asan Medical Center
Seoul, , 5505
Status
Recruiting
Address
Local Institution - 902
Seoul, , 5505
Status
Completed
Address
Local Institution - 402
Maastricht, , 6229 HX
Status
Recruiting
Address
UMC Maastricht
Maastricht, , 6229 HX
Status
Recruiting
Address
Radboud University Medical Center
Nijmegen, , 6525 GA
Status
Recruiting
Address
Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
Poznan, , 60-569
Status
Recruiting
Address
Instytut Hematologii i Transfuzjologii w Warszawie
Warszawa, , 02-776
Status
Recruiting
Address
Local Institution - 801
Warszawa, , 02-776
Status
Recruiting
Address
Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
Wroclaw, , 50-556
Status
Terminated
Address
FSBI Hematology Research Center Ministry of Healthcare of the Russian Federation
Moscow, , 125167
Status
Terminated
Address
Moscow State Healthcare Institution City clinical hospital n.a. S.P.Botkin
Moscow, , 125284
Status
Terminated
Address
City Clinical Hospital 40
Moscow, , 129301
Status
Terminated
Address
Novosibirsk State Medical University (NSMU)
Novosibirsk, , 630066
Status
Terminated
Address
Russian Research Institute of Hematology and Transfusiology of the Federal Biomedical Agency
Saint Petersburg, , 191024
Status
Terminated
Address
Pavlov First Saint Petersburg State Medical University
Saint-Petersburg, , 197022
Status
Terminated
Address
Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov
St Petersburg, , 197341
Status
Recruiting
Address
Local Institution - 859
Vladikavkaz, , 362002
Status
Terminated
Address
State Budgetary Healthcare Organization
Vladikavkaz, , 362002
Status
Not yet recruiting
Address
Complejo Hospitalario Universitario A Coruna
A Coruna, , 15006
Status
Recruiting
Address
Hospital General Universitario de Alicante
Alicante, , 03010
Status
Recruiting
Address
Local Institution - 451
Alicante, , 03010
Status
Recruiting
Address
Hospital Universitari Germans Trias i Pujol
Badalona (Barcelona), , 8916
Status
Recruiting
Address
Hospital Universitario Cruces
Barakaldo, , 48903
Status
Recruiting
Address
Hospital Clinic de Barcelona
Barcelona, , 08036
Status
Recruiting
Address
Instituto Catalan de Oncologia de Girona
Gerona, , 17007
Status
Recruiting
Address
Hospital Universitario de Gran Canaria Dr. Negrin
Las Palmas de Gran Canaria, , 35012
Status
Recruiting
Address
Hospital Ramon y Cajal
Madrid, , 28034
Status
Recruiting
Address
Hospital Universitario 12 de Octubre
Madrid, , 28041
Status
Recruiting
Address
Hospital Universitario Virgen de la Victoria
Malaga, , 29010
Status
Recruiting
Address
Local Institution - 457
Malaga, , 29010
Status
Recruiting
Address
Hospital General Universitario Morales Meseguer
Murcia, , 30008
Status
Recruiting
Address
Universitario de Salamanca - Hospital Clinico
Salamanca, , 37007
Status
Recruiting
Address
Hospital Universitario de Tenerife
Santa Cruz de Tenerife, , 38320
Status
Recruiting
Address
Hospital Clinico Universitario de Santiago
Santiago de Compostela, , 15706
Status
Completed
Address
Local Institution - 460
Santiago de Compostela, , 15706
Status
Recruiting
Address
Hospital Clinico Universitario de Valencia
Valencia, , 46010
Status
Completed
Address
Local Institution - 456
Valencia, , 46010
Status
Recruiting
Address
University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
Birmingham, , B15 2TH
Status
Recruiting
Address
United Lincolnshire Hospitals NHS Trust
Boston, , PE21 9QS
Status
Recruiting
Address
Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
London, , SE1 9RT
Status
Recruiting
Address
Imperial College Hammersmith Hospital
London, , W12 0HS
Status
Recruiting
Address
The Christie NHS Foundation Trust
Manchester, , M20 4BX
Status
Completed
Address
Nottingham City Hospital
Nottingham, , NG5 1PB
Status
Recruiting
Address
The Churchill Hospital
Oxford, , 0X3 7LE