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

NCT03952039 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: FEDR-MF-002U1111-1223-29622018-003411-21
• Study Type: interventional
• Target: 202
• Locations: 15 countries
• Sites: 102

Brief Summary

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.

Conditions

Primary Myelofibrosis; Post-Polycythemia Vera; Myelofibrosis

Keywords

MF; myeloproliferative neoplasms; MPN; myelofibrosis; PMF; post-PV; Post-Polycythemia Vera; post-ET MF; Post-Essential Thrombocythemia Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Spleen Volume Response Rate (RR)

  Percentage of participants who have ≥ 35% spleen volume reduction (SVR) at end of cycle 6 A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.

  From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days

Secondary Outcomes (14)

• Symptom Response Rate (SRR)

  From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

• Spleen Volume Response Rate (RR25)

  From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days

• Number of Participants With All Grade Treatment Emergent Adverse Events (AEs) and Grade 3 to 4 Treatment Emergent AEs

  From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

• Number of Participants With Hematology Laboratory Abnormalities

  From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

• Spleen Response Rate by Palpation (RRP)

  From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

Study Arms (2)

Fedratinib 400mg/day

EXPERIMENTAL

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.

Drug: FEDRATINIB

Best Available Therapy (BAT)

ACTIVE COMPARATOR

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.

Drug: Best Available Therapy (BAT)

Interventions

FEDRATINIB DRUG

A potent and selective inhibitor of JAK2 kinase activity

Fedratinib 400mg/day

Best Available Therapy (BAT) DRUG

Best available therapy (BAT)

Best Available Therapy (BAT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is at least 18 years of age at the time of signing the informed consent form (ICF)
• Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0, 1 or 2
• 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
• Subject has a DIPSS Risk score of Intermediate-2 or High
• 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
• Subject has a measurable total symptoms score (≥ 1) as measured by the Myelofibrosis Symptom Assessment Form (MFSAF)
• Subject has been previously exposed to ruxolitinib, and must meet at least one of the following criteria (a and/or b)
• 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
• 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
• Subject must have treatment-related toxicities from prior therapy resolved to Grade 1 or pretreatment baseline before start of last therapy prior to randomization
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements
• A female of childbearing potential (FCBP) must:

You may not qualify if:

• Any of the following laboratory abnormalities:
• Platelets \< 50 x 109/L
• Absolute neutrophil count (ANC) \< 1.0 x 109/L
• White blood count (WBC) \> 100 x 109/L
• Myeloblasts ≥ 5 % in peripheral blood
• Estimated glomerular filtration rate \< 30 mL/min/1.73 m2 (as per the Modification of Diet in Renal Disease \[MDRD\] formula)
• Serum amylase or lipase \> 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 x upper limit of normal (ULN)
• 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
• Subject is pregnant or lactating female
• Subject with previous splenectomy
• Subject with previous or planned hematopoietic cell transplant
• Subject with prior history of encephalopathy, including Wernicke's (WE)
• Subject with signs or symptoms of encephalopathy, including WE (eg, severe ataxia, ocular paralysis or cerebellar signs)
• Subject with thiamine deficiency, defined as thiamine levels in whole blood below normal range according to the central laboratory and not demonstrated to be corrected prior to randomization

Sponsors & Collaborators

• Celgene: lead
• Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation: collaborator

Study Sites (107)

Local Institution - 103

Darlinghurst, New South Wales, 2010, Australia

Location

Local Institution - 101

Adelaide, South Australia, 5000, Australia

Location

Local Institution - 105

Box Hill, Victoria, 3128, Australia

Location

Local Institution - 102

Langwarrin, Victoria, 3910, Australia

Location

Local Institution - 100

Melbourne, 3004, Australia

Location

Local Institution - 156

Graz, 73013, Austria

Location

Local Institution - 154

Innsbruck, 6020, Austria

Location

Local Institution - 155

Linz, 4020, Austria

Location

Local Institution - 151

Salzburg, 5020, Austria

Location

Local Institution - 150

Vienna, 1090, Austria

Location

Local Institution - 152

Vienna, 1140, Austria

Location

Local Institution - 153

Wels, 4600, Austria

Location

Local Institution - 200

Bruges, 8000, Belgium

Location

Local Institution - 202

Brussels, 1200, Belgium

Location

Local Institution - 205

La Louvière-(Haine St-Paul), 7100, Belgium

Location

Local Institution - 201

Leuven, 3000, Belgium

Location

Local Institution - 204

Liège, 4000, Belgium

Location

Local Institution - 203

Yvoir, 5530, Belgium

Location

Local Institution - 555

Beijing, 100044, China

Location

Local Institution - 550

Guangzhou, Guangdong, 510080, China

Location

Local Institution - 553

Tianjin, 300041, China

Location

Local Institution - 557

Zhengzhou, 0, China

Location

Local Institution - 700

Brno, 625 00, Czechia

Location

Local Institution - 702

Ostrava-Poruba, 708 52, Czechia

Location

Local Institution - 701

Prague, 128 08, Czechia

Location

Local Institution - 255

Angers, 49033, France

Location

Local Institution - 256

Brest, 29200, France

Location

Local Institution - 254

Lens, 62307, France

Location

Local Institution - 259

Lille, 59037, France

Location

Local Institution - 260

Nice, 06200, France

Location

Local Institution - 250

Nîmes, 30029, France

Location

Local Institution - 252

Paris, 75010, France

Location

Local Institution - 258

Pessac, 33604, France

Location

Local Institution - 257

Pierre-Bénite, 69495, France

Location

Local Institution - 261

Poitiers, 86021, France

Location

Local Institution - 251

Strasbourg, 67091, France

Location

Local Institution - 253

Toulouse, 31059, France

Location

Local Institution - 302

Aachen, 52074, Germany

Location

Local Institution - 308

Frankfurt am Main, 60590, Germany

Location

Local Institution - 306

Halle, 06120, Germany

Location

Local Institution - 303

Jena, 07747, Germany

Location

Local Institution - 307

Magdeburg, 39120, Germany

Location

Local Institution - 301

Mannheim, 68167, Germany

Location

Local Institution - 304

Minden, 32429, Germany

Location

Local Institution - 305

Ulm, 89081, Germany

Location

Local Institution - 600

Budapest, 1088, Hungary

Location

Local Institution - 601

Győr, 9024, Hungary

Location

Local Institution - 602

Kaposvár, 7400, Hungary

Location

Local Institution - 604

Nyíregyháza, 4400, Hungary

Location

Local Institution - 603

Szeged, 6720, Hungary

Location

Local Institution - 751

Cork, T12 DFK4, Ireland

Location

Local Institution - 752

Dublin, Dublin 7, Ireland

Location

Local Institution - 750

Dublin, Dublin 8, Ireland

Location

Local Institution - 353

Bologna, 40138, Italy

Location

Local Institution - 363

Brescia, 25123, Italy

Location

Local Institution - 354

Catania, 95123, Italy

Location

Local Institution - 350

Florence, 50134, Italy

Location

Local Institution - 358

Milan, 20122, Italy

Location

Local Institution - 362

Naples, 80131, Italy

Location

Local Institution - 357

Pavia, 27100, Italy

Location

Local Institution - 356

Roma, 00168, Italy

Location

Local Institution - 361

Roma, 00168, Italy

Location

Local Institution - 359

Roma, 00189, Italy

Location

Local Institution - 355

Torino, 10126, Italy

Location

Local Institution - 360

Udine, 33100, Italy

Location

Local Institution - 352

Varese, 21100, Italy

Location

Local Institution - 364

Verona, 37134, Italy

Location

Local Institution - 402

Maastricht, 6229 HX, Netherlands

Location

Local Institution - 400

Nijmegen, 6525 GA, Netherlands

Location

Local Institution - 803

Poznan, 61-848, Poland

Location

Local Institution - 801

Warsaw, 02-776, Poland

Location

Local Institution - 802

Wroclaw, 50-556, Poland

Location

Local Institution - 855

Moscow, 125167, Russia

Location

Local Institution - 851

Moscow, 125284, Russia

Location

Local Institution - 853

Moscow, 129301, Russia

Location

Local Institution - 857

Novosibirsk, 630066, Russia

Location

Local Institution - 852

Saint Petersburg, 191024, Russia

Location

Local Institution - 854

Saint Petersburg, 197022, Russia

Location

Local Institution - 850

Saint Petersburg, 197341, Russia

Location

Local Institution - 859

Vladikavkaz, 362002, Russia

Location

Local Institution - 900

Seongnam-si, 13620, South Korea

Location

Local Institution - 905

Seoul, 06351, South Korea

Location

Local Institution - 901

Seoul, 06591, South Korea

Location

Local Institution - 903

Seoul, 140-887, South Korea

Location

Local Institution - 904

Seoul, 3080, South Korea

Location

Local Institution - 902

Seoul, 5505, South Korea

Location

Local Institution - 451

Alicante, 03010, Spain

Location

Local Institution - 452

Badalona (Barcelona), 8916, Spain

Location

Local Institution - 458

Barakaldo, 48903, Spain

Location

Local Institution - 450

Barcelona, 08036, Spain

Location

Local Institution - 462

Girona, 17007, Spain

Location

Local Institution - 461

Las Palmas de Gran Canaria, 35012, Spain

Location

Local Institution - 453

Madrid, 28034, Spain

Location

Local Institution - 459

Madrid, 28041, Spain

Location

Local Institution - 457

Málaga, 29010, Spain

Location

Local Institution - 454

Murcia, 30008, Spain

Location

Local Institution - 455

Salamanca, 37007, Spain

Location

Local Institution - 463

Santa Cruz de Tenerife, 38320, Spain

Location

Local Institution - 460

Santiago de Compostela, 15706, Spain

Location

Local Institution - 456

Valencia, 46010, Spain

Location

Local Institution - 504

Manchester, Lancashire, M20 4BX, United Kingdom

Location

Local Institution - 506

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Local Institution - 502

Birmingham, B15 2TH, United Kingdom

Location

Local Institution - 503

Boston, PE21 9QS, United Kingdom

Location

Local Institution - 501

London, SE1 9RT, United Kingdom

Location

Local Institution - 505

London, W12 0HS, United Kingdom

Location

Local Institution - 500

Oxford, 0X3 7LE, United Kingdom

Location

Related Publications (1)

• Harrison CN, Mesa R, Talpaz M, Al-Ali HK, Xicoy B, Passamonti F, Palandri F, Benevolo G, Vannucchi AM, Mediavilla C, Iurlo A, Kim I, Rose S, Brown P, Hernandez C, Wang J, Kiladjian JJ. Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Haematol. 2024 Oct;11(10):e729-e740. doi: 10.1016/S2352-3026(24)00212-6. Epub 2024 Sep 9.

  PMID: 39265613 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Primary Myelofibrosis; Myeloproliferative Disorders

Interventions

fedratinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: May 16, 2019
• Study Start: September 9, 2019
• Primary Completion: December 15, 2022
• Study Completion: July 28, 2025
• Last Updated: August 28, 2025
• Results First Posted: January 30, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

AU (7); HU (5); GB (7); CZ (3); RU (8); BE (6); IT (14); DE (8); ES (14); NL (2); IE (3); KR (6); FR (12); PL (3); CN (4)