A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib

NCT03755518 | Terminated Phase 3 Results FDA Drug

• 3 other identifiers: FEDR-MF-001U1111-1223-28622018-002237-38
• Study Type: interventional
• Target: 38
• Locations: 2 countries
• Sites: 35

Brief Summary

This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib 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 a 35% reduction in spleen size and one of the secondary objectives is to evaluate the safety of fedratinib.

Conditions

Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis

Keywords

Myelofibrosis (MF); Primary Myelofibrosis (PMF); Post-Polycythemia Vera Myelofibrosis (Post-PV); Post-essential thrombocythemia Myelofibrosis (Post-ET); Myeloproliferative neoplasms (MPN)

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6

  Percentage of participants who have a ≥ 35% SVR at end of Cycle 6 as compared to baseline. Participants with a missing MRI/CT spleen volume at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered non-responders. Baseline value is defined as the last value or measurement taken prior to the first dose in the study

  From First Dose to end of Cycle 6 (approximately 168 days)

Secondary Outcomes (17)

• Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs

  From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 128 weeks)

• Number of Participants and Severity of Treatment Related All Grade Adverse Events (AEs) and Grade 3/4 AEs

  From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 124 weeks)

• Mean Change From Baseline in Hematology Laboratory Analysis - Hemoglobin

  at Cycle 4 Day 1 and Cycle 7 Day 1

• Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes

  at Cycle 4 Day 1 and Cycle 7 Day 1

• Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils

  at Cycle 4 Day 1 and Cycle 7 Day 1

Study Arms (1)

Administration of Fedratinib 400mg/day

EXPERIMENTAL

Self-administered Investigational Product (IP) (400 mg/day) on an outpatient basis, once daily preferably with food during an evening meal at the same time each day in consecutive 4-week (28-day) cycles.

Drug: FEDRATINIB

Interventions

FEDRATINIB DRUG

A potent and selective inhibitor of JAK2 kinase activity

Administration of Fedratinib 400mg/day

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 or High
• Subject has a measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥ 450 cm3 by MRI or CT-scan assessment or by palpable spleen measuring ≥ 5 cm below the left costal margin.
• Subject has been previously exposed to ruxolitinib, while diagnosed with MF (PMF, post-ET MF or post-PV MF), and must meet at least one of the following criteria (a or b)
• Treatment with ruxolitinib for ≥ 3 months
• Treatment with ruxolitinib for ≥ 28 days complicated by any of the following:
• 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 fedratinib treatment.
• 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
• Participants must agree to use effective contraception

You may not qualify if:

• Any of the following laboratory abnormalities:
• Platelets \< 50,000/μL
• Absolute neutrophil count (ANC) \< 1.0 x 109/L
• White blood count (WBC) \> 100 x 10\^9/L
• Myeloblasts \> 5 % in peripheral blood
• Estimated glomerular filtration rate \< 30 mL/min/1.73 m\^2 (as per the Modification of Diet in Renal Disease \[MDRD\] formula)
• Serum amylase or lipase \> 1.5 x ULN (upper limit of normal)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 x 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
• Subject with signs or symptoms of encephalopathy including Wernicke's (eg, severe ataxia, ocular paralysis or cerebellar signs)
• Subject with thiamine deficiency, defined as thiamine levels in whole blood below normal range according to institutional standard and not corrected prior to enrollment on the study

Sponsors & Collaborators

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

Study Sites (35)

Local Institution - 117

Aurora, Colorado, 80045, United States

Location

Local Institution - 126

Miami, Florida, 33176, United States

Location

Local Institution - 113

Augusta, Georgia, 30912, United States

Location

Local Institution - 112

Chicago, Illinois, 60612, United States

Location

Local Institution - 109

Chicago, Illinois, 60637, United States

Location

Local Institution - 121

Park Ridge, Illinois, 60068, United States

Location

Local Institution - 100

Kansas City, Kansas, 66160-7314, United States

Location

Local Institution - 123

Baltimore, Maryland, 21229-5299, United States

Location

Local Institution - 118

Bethesda, Maryland, 20817, United States

Location

Local Institution - 127

Columbia, Maryland, 21044, United States

Location

Local Institution - 103

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 101

St Louis, Missouri, 63110, United States

Location

Local Institution - 128

Newark, New Jersey, 07112-2027, United States

Location

Local Institution - 130

Brooklyn, New York, 11212, United States

Location

Local Institution - 115

New York, New York, 10029, United States

Location

Local Institution - 124

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Local Institution - 105

Chapel Hill, North Carolina, 27514, United States

Location

Local Institution - 114

Durham, North Carolina, 27705, United States

Location

Local Institution - 111

Cincinnati, Ohio, 45219, United States

Location

Local Institution - 106

Pittsburgh, Pennsylvania, 15224, United States

Location

Local Institution - 108

Sioux Falls, South Dakota, 57105, United States

Location

Local Institution - 119

Dallas, Texas, 75390-8852, United States

Location

Local Institution - 132

Fort Worth, Texas, 76104, United States

Location

Local Institution - 110

Houston, Texas, 77303, United States

Location

Local Institution - 120

San Antonio, Texas, 78229, United States

Location

Local Institution - 116

Seattle, Washington, 98109, United States

Location

Local Institution - 129

Madison, Wisconsin, 53792-2454, United States

Location

Local Institution - 203

Vancouver, British Columbia, V6Z 2A5, Canada

Location

Local Institution - 207

London, Ontario, N6C 6B5, Canada

Location

Local Institution - 205

Ottawa, Ontario, K1H 8L6, Canada

Location

Local Institution - 200

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 201

Montreal, Quebec, H1T 2M4, Canada

Location

Local Institution - 202

Montreal, Quebec, H3T 1E2, Canada

Location

Local Institution - 204

Sherbrooke, Quebec, J1K 2R1, Canada

Location

Related Publications (1)

• Gupta V, Yacoub A, Mesa RA, Harrison CN, Vannucchi AM, Kiladjian JJ, Deeg HJ, Fazal S, Foltz L, Mattison RJ, Miller CB, Parameswaran V, Brown P, Hernandez C, Wang J, Talpaz M. Safety and efficacy of fedratinib in patients with myelofibrosis previously treated with ruxolitinib: primary analysis of FREEDOM trial. Leuk Lymphoma. 2024 Sep;65(9):1314-1324. doi: 10.1080/10428194.2024.2346733. Epub 2024 Jun 5.

  PMID: 38838026 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

1-855-907-3286

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 28, 2018
• Study Start: March 27, 2019
• Primary Completion: November 26, 2021
• Study Completion: November 8, 2023
• Last Updated: December 12, 2024
• Results First Posted: March 9, 2023

Record last verified: 2024-12

Locations

US (28); CA (7)