Primary MyelofibrosisPhase 3FREEDOMNCT03755518
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
A Phase 3 study testing FEDRATINIB in people with Primary Myelofibrosis and Post-Polycythemia Vera Myelofibrosis, run by Celgene at 35 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Myelofibrosis
- What is being tested?
- FEDRATINIB
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 35 sitesin 2 countries
- Study dates
- 27 Mar 2019to 8 Nov 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Main Study Inclusion Criteria
- 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.
Show all 15Show fewer
- 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
Who cannot join
- Main Study Exclusion Criteria
- 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
Show all 36Show fewer
- 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
- Subject with concomitant treatment with or use of pharmaceutical, herbal agents or food known to be strong or moderate inducers of Cytochrome P450 3A4 (CYP3A4), or dual CYP2C19 and CYP3A4 inhibitors
- Subject on any chemotherapy, immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), anagrelide, immunosuppressive therapy, systemic corticosteroids > 10 mg/day prednisone or equivalent. Subjects who have had prior exposure to hydroxyurea (eg, Hydrea) in the past may be enrolled into the study as long as it has not been administered within 14 days prior to the start of fedratinib treatment
- Subject has received ruxolitinib within 14 days prior to the start of fedratinib
- Subject on treatment with myeloid growth factor (eg, granulocyte-colony stimulating factor [G-CSF]) within 14 days prior to the start of fedratinib treatment
- Subject with previous exposure to Janus kinase (JAK) inhibitor(s) for more than 1 cycle other than ruxolitinib treatment
- Subject on treatment with aspirin with doses > 150 mg daily
- Subject with major surgery within 28 days before starting fedratinib treatment
- Subject with diagnosis of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemochromatosis, non-alcoholic steatohepatitis)
- Subject with prior malignancy other than the disease under study unless the subject has not required treatment for the malignancy for at least 3 years prior to enrollment.
- However, subject with the following history/concurrent conditions provided successfully treated may enroll: non-invasive skin cancer, in situ cervical cancer, carcinoma in situ of the breast, incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system), or is free of disease and on hormonal treatment only
- Subject with uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4)
- Subject with known human immunodeficiency virus (HIV), known active infectious Hepatitis B (HepB), and/or known active infectious Hepatitis C (HepC)
- Subject with serious active infection
- Subject with presence of any significant gastric or other disorder that would inhibit absorption of oral medication
- Subject is unable to swallow capsule
- Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
- Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- Subject has any condition that confounds the ability to interpret data from the study
- Subject with participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to start of fedratinib treatment
- Subject with life expectancy of less than 6 months.
Trial locations and contacts
35 sites in 2 countries.
35 sites in 2 countries
United States28 sites
Local Institution - 103
Ann Arbor, Michigan, 48109
Local Institution - 113
Augusta, Georgia, 30912
Local Institution - 117
Aurora, Colorado, 80045
Local Institution - 123
Baltimore, Maryland, 21229-5299
Local Institution - 118
Bethesda, Maryland, 20817
Local Institution - 130
Brooklyn, New York, 11212
Local Institution - 105
Chapel Hill, North Carolina, 27514
Local Institution - 112
Chicago, Illinois, 60612
Local Institution - 109
Chicago, Illinois, 60637
Local Institution - 111
Cincinnati, Ohio, 45219
Local Institution - 127
Columbia, Maryland, 21044
Local Institution - 119
Dallas, Texas, 75390-8852
Local Institution - 114
Durham, North Carolina, 27705
Local Institution - 132
Fort Worth, Texas, 76104
Local Institution - 110
Houston, Texas, 77303
Local Institution - 100
Kansas City, Kansas, 66160-7314
Local Institution - 129
Madison, Wisconsin, 53792-2454
Local Institution - 126
Miami, Florida, 33176
Local Institution - 115
New York, New York, 10029
Local Institution - 124
New York, New York, 10032
Local Institution - 128
Newark, New Jersey, 07112-2027
Local Institution - 121
Park Ridge, Illinois, 60068
Local Institution - 106
Pittsburgh, Pennsylvania, 15224
Local Institution - 120
San Antonio, Texas, 78229
Local Institution - 116
Seattle, Washington, 98109
Local Institution - 108
Sioux Falls, South Dakota, 57105
Local Institution - 101
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210
Canada7 sites
Local Institution - 207
London, Ontario, N6C 6B5
Local Institution - 201
Montreal, Quebec, H1T 2M4
Local Institution - 202
Montreal, Quebec, H3T 1E2
Local Institution - 205
Ottawa, Ontario, K1H 8L6
Local Institution - 204
Sherbrooke, Quebec, J1K 2R1
Local Institution - 200
Toronto, Ontario, M5G 2M9
Local Institution - 203
Vancouver, British Columbia, V6Z 2A5
About this study
Official title: A Phase 3b, Multicenter, Single-Arm, Open-Label Efficacy and Safety Study 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
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.
Read the detailed description
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 spleen volume reduction at the end of Cycle 6 as the primary objective. The secondary objectives of the study are to further evaluate the safety and to assess and implement mitigation strategies for WE and for gastrointestinal (GI) adverse events.
The study will be at multiple centers to provide access to a broad population and have assurance the results are likely to have general applicability.
This is also conducted as an open-label study to collect efficacy and safety data with fedratinib use, no randomization or stratification will occur.
- Conditions
- Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis
- Being tested
- FEDRATINIB
- Keywords
- Myelofibrosis (MF), Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV), Post-essential thrombocythemia Myelofibrosis (Post-ET), Myeloproliferative neoplasms (MPN)
- Medical subject headings
- Primary Myelofibrosis, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FEDRATINIBDrug
A potent and selective inhibitor of JAK2 kinase activity
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: FEDRATINIB |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Number of participants and severity of all grade adverse events (AEs) and grade 3/4 AEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.
Measured: 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
Number of participants and severity of treatment related all grade adverse events (AEs) and grade 3/4 AEs as per NCI CTCAE.
Measured: 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
Mean change from baseline in hematology laboratory analysis - hemoglobin
Measured: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes
Mean change from baseline in hematology laboratory analysis - erythrocytes.
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
Measured: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils
Mean change from baseline in hematology laboratory analysis - platelets, leukocytes and neutrophils.
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
Measured: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis
Mean change from baseline in hematology laboratory analysis - blasts/leukocytes
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
Measured: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase
Mean change from baseline in chemistry parameters analysis - ALT, AST, Amylase, Lipase
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
Measured: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine
Mean change from baseline in chemistry parameters analysis - Creatinine.
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
Measured: at Cycle 4 Day 1 and Cycle 7 Day 1
Spleen Response Rate by Palpation
Spleen response rate by palpation is the percentage of participants with a spleen response according to the IWG-MRT 2013 at the end of Cycle 6 as compared to baseline. This will be calculated for participants that have an enlarged spleen (≥ 5 cm below LCM) at baseline. Participants with a missing spleen size assessment 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 not to be responders.
Measured: From First Dose to end of Cycle 6 (approximately 168 days)
Symptom Response Rate
Symptom response rate (SRR) is defined as the percentage of participants with ≥ 50% reduction from baseline to the end of Cycle 6 in total symptom score (TSS) measured by MFSAF version 4.0. The TSS will be defined as the sum of each of the 7 symptom scores. Participants without a baseline TSS > 0 will be considered non-evaluable (due to no place for symptom reduction) for the SRR analysis. Participants with a missing TSS at the end of Cycle 6 or who had disease progression before the end of the Cycle 6 will be considered non-responders.
Measured: From First Dose to end of Cycle 6 (approximately 168 days)
Durability of Spleen Volume Response by MRI/CT (DR)
Durability of spleen volume response (DR) by MRI/CT is defined as time from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) (ie, ≥ 25% increase in spleen volume from baseline) or death, whichever is earlier. In the absence an event (ie, subsequent spleen volume reduction < 35% before the analysis is performed), the DR will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen volume response by MRI/CT scan will be analyzed using Kaplan-Meier method.
Measured: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 59.40 Weeks)
Durability of Spleen Response by Palpation (DRP)
Durability of spleen response by palpation (DRP) is defined as time from the date of first documented palpable spleen response, according to the IWG-MRT 2013 to the date of subsequent PD according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event (ie, no loss of spleen response by palpation) before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen response by palpation will be analyzed using Kaplan-Meier (K-M) method.
Measured: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 59.32 Weeks)
Durability of Symptom Response (DSR)
Durability of symptoms response is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction < 50%. In the absence of TSS reduction < 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.
Measured: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 31.33 Weeks)
Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's.
Number of participants with grade 3 or higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy including Wernicke's.
Measured: From first dose to end of treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN).
Number of participants with thiamine levels < LLN.
LLN of thiamine is 70 nmol/L.
Measured: At Cycle 1, 2, 3, and every 3 cycles afterwards till End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN).
Number of participants with thiamine levels > ULN.
ULN of thiamine is 180 nmol/L.
Measured: At Cycle 1, 2, 3, and every 3 cycles afterwards till End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4
Number of participants with clinically notable laboratory results, Grade 3 or 4
Measured: From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 124 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2018
- Study start27 Mar 2019
- Primary completion26 Nov 2021
- Study completion8 Nov 2023
Why it stopped: Slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary MyelofibrosisStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03755518
- Sponsor's protocol ID
- FEDR-MF-001
- Other IDs
- U1111-1223-2862, 2018-002237-38, 2018
- Acronym
- FREEDOM
- Status last verified
- Dec 2024
- First submitted
- 8 Nov 2018
- Last updated
- 12 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Publications
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.
PubMed 38838026
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3b, Multicenter, Single-Arm, Open-Label Efficacy and Safety Study 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
- ClinicalTrials.gov ID
- NCT03755518
- Acronym / sponsor ID
- FREEDOM / FEDR-MF-001
- 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)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual.
- Enrolment
- 38 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Collaborators
- Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation
- Study start
- 27 Mar 2019 (actual)
- Primary completion
- 26 Nov 2021 (actual)
- Study completion
- 8 Nov 2023 (actual)
- First posted
- 28 Nov 2018 (actual)
- Results
- Posted 9 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 spleen volume reduction at the end of Cycle 6 as the primary objective. The secondary objectives of the study are to further evaluate the safety and to assess and implement mitigation strategies for WE and for gastrointestinal (GI) adverse events.
The study will be at multiple centers to provide access to a broad population and have assurance the results are likely to have general applicability.
This is also conducted as an open-label study to collect efficacy and safety data with fedratinib use, no randomization or stratification will occur.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Administration of Fedratinib 400mg/day | Experimental | Drug: FEDRATINIBSelf-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Main Study Inclusion Criteria
- 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
Key exclusion criteria (36 listed)
- Main Study Exclusion Criteria
- Any of the following laboratory abnormalities:
- Subject is pregnant or lactating female
- Subject with previous splenectomy
- Subject with previous or planned hematopoietic cell transplant
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 |
|---|---|---|
| FEDRATINIBA potent and selective inhibitor of JAK2 kinase activity | Drug | Administration of Fedratinib 400mg/day |
Primary outcome
Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6
Time frame: From First Dose to end of Cycle 6 (approximately 168 days)
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
17 secondary outcomes
Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs
Time frame: 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
Time frame: 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
Time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes
Time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils
Time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis
Time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase
Time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine
Time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
Spleen Response Rate by Palpation
Time frame: From First Dose to end of Cycle 6 (approximately 168 days)
Symptom Response Rate
Time frame: From First Dose to end of Cycle 6 (approximately 168 days)
Durability of Spleen Volume Response by MRI/CT (DR)
Time frame: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 59.40 Weeks)
Durability of Spleen Response by Palpation (DRP)
Time frame: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 59.32 Weeks)
Durability of Symptom Response (DSR)
Time frame: From Cycle 1 Day 1 up to 30 days after last dose (Approximately an average of 31.33 Weeks)
Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's.
Time frame: From first dose to end of treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN).
Time frame: At Cycle 1, 2, 3, and every 3 cycles afterwards till End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN).
Time frame: At Cycle 1, 2, 3, and every 3 cycles afterwards till End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
Number of Participants With Clinically Notable Laboratory Results, Grade 3 or 4
Time frame: From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 124 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38838026Gupta 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.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
35 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing FEDRATINIB in people with Primary Myelofibrosis and Post-Polycythemia Vera Myelofibrosis, run by Celgene at 35 sites in 2 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 15 inclusion and 36 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: stopped early, as of the sponsor's last update on 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Canada. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 9 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6 (time frame: From First Dose to end of Cycle 6 (approximately 168 days)). 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 NCT03755518, 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 12 Dec 2024.