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Primary MyelofibrosisPhase 1/2NCT04446650

A Study of Fedratinib in Japanese 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)

A Phase 1/2 study testing Fedratinib in people with Primary Myelofibrosis, run by Bristol-Myers Squibb at 21 sites in Japan.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Primary Myelofibrosis
What is being tested?
Fedratinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
21 sitesJapan
Study dates
12 Oct 2020to 30 Nov 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must satisfy the following criteria to be enrolled in the study:
  • Subject is ≥ 20 years of age at the time of signing the informed consent form (ICF)
  • Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (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- Polycythemia vera (PV) Myelofibrosis (MF) according to the IWG-MRT 2007 criteria, confirmed by the most recent local pathology report
  • Subject has a Dynamic International Prognostic Scoring System (DIPSS) Risk score of Intermediate-1 with symptom(s), Intermediate-2 or High
  • Subject has a measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥ 450 cm3 by magnetic resonance imaging (MRI) or computed tomography (CT) scan or by palpable spleen measuring ≥ 5 cm below the left costal margin.
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  • Subject must meet at least one of the following criteria of (a or b).
  • Note: reason to discontinue ruxolitinib treatment (lack of efficacy and/or intolerability, etc) and physician decision as to the study participation as being appropriate should be recorded in the case report form:
  • Previously received ruxolitinib treatment for PMF or post-PV MF or post-ET MF for at least 14 days (exposure of < 14 days is allowed for subjects who discontinued ruxolitinib due to intolerability or allergy).
  • Never received ruxolitinib treatment and is expected to derive clinical benefit from this study participation based on the clinical judgement of the Investigator Only those subjects who previously received ruxolitinib treatment are eligible for the Phase 1 part of the study to avoid overestimating tolerability of fedratinib.
  • Subject must have treatment-related toxicities from prior therapy resolved to Grade 1 or pretreatment baseline before start of last therapy prior to starting the 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.
  • A female of childbearing potential (FCBP) must:
  • Have 2 negative pregnancy tests as verified by the Investigator during screening prior to starting fedratinib treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of fedratinib treatment. This applies even if the subject practices true abstinence* from heterosexual contact.
  • Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use and be able to comply with highly effective contraception** without interruption, -14 days prior to starting investigational product, during the fedratinib treatment (including dose interruptions), and for 30 days after discontinuation of fedratinib treatment.
  • If breastfeeding, agree to stop breastfeeding prior to the participation in the study and not to resume breastfeeding for at least 30 days after treatment discontinuation of the fedratinib treatment.
  • Note: A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy or amenorrhea due to other medical reasons does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
  • A male subject must:
  • Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 30 days following fedratinib discontinuation, or longer if required by local regulations, even if he has undergone a successful vasectomy.
  • True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception).
  • Agreement to use highly effective methods of contraception that alone or in combination resulting in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly throughout the course of the study. Such methods include combined (estrogen and progestogen containing) hormonal contraception (oral), progestogen-only hormonal contraception associated with inhibition of ovulation (oral), placement of an intrauterine device, placement of an intrauterine hormone-releasing system, bilateral tubal occlusion, and vasectomized partner.

Who cannot join

  • The presence of any of the following will exclude a subject from enrollment:
  • Any of the following laboratory abnormalities:
  • Platelets < 50 x 109/L (without platelet transfusion)
  • Absolute neutrophil count (ANC) < 1.0 x 109/L
  • White blood count (WBC) > 100 x 109/L
  • Myeloblasts ≥ 5 % in peripheral blood
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  • Estimated creatinine clearance < 30 mL/min (as estimated by Cockcroft-Gault formula)
  • Serum amylase or lipase > 1.5 x upper limit of normal
  • 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 breastfeeding female.
  • Subject with previous splenectomy
  • Subject with previous or planned hematopoietic Stem-cell transplantation (SCT)
  • Subject with prior history of Encephalopathy, including Wernicke encephalopathy (WE)
  • Subject with signs or symptoms of encephalopathy, including WE (eg, severe ataxia, ocular paralysis or cerebellar signs) without documented exclusion of WE by thiamine level and brain MRI
  • Subject with thiamine deficiency, defined as thiamine levels in whole blood below normal range according to institutional standard and not demonstrated to be corrected prior to starting the fedratinib treatment
  • Subject with concomitant treatment with or use of pharmaceutical, herbal agents or food known to be strong or moderate inducers of Cytochrome P450 (CYP) 3A4, and 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 starting the fedratinib treatment.
  • Subject on treatment with myeloid growth factor (eg, granulocyte-colony stimulating factor [G-CSF]) within 14 days prior to starting the fedratinib treatment
  • Subject with previous exposure to JAK inhibitor(s) other than ruxolitinib treatment
  • Subject has received ruxolitinib within 14 days prior to starting the fedratinib treatment
  • Subject on treatment with aspirin with doses > 150 mg daily
  • Subject with major surgery within 28 days prior to starting the 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 the start of fedratinib treatment. 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)
  • Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV)
  • Subject who are hepatitis B surface antigen (HBsAg) negative but HB core anti-body (HBcAb) positive or HBsAb positive are eligible in case HBV viral deoxyribonucleoside (DNA) negative
  • Subject who had HBsAg positive but show non-detectable viral DNA for at least 6 months prior to starting the fedratinib treatment where appropriate anti-viral treatment should have been given/considered to prevent HBV reactivation based on the standard practice are eligible
  • Subject who are seropositive because of hepatitis B virus vaccine are eligible
  • Seropositive for and with active viral infection with hepatitis C virus (HCV)
  • Subject who had hepatitis C but show no detectable HCV viral ribonucleotide (RNA) for at least 6 months prior to starting the fedratinib treatment are eligible.
  • Evidence of human immunodeficiency virus (HIV) infection.
  • Subject with serious active infection
  • Additionally, subject with history of active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 4 weeks prior to screening, unless the subject has adequately recovered from coronavirus disease (COVID) symptoms and related complications as per investigator's discretion, and following a discussion with the Medical Monitor.
  • Subject with presence of any significant gastric or other disorder that would inhibit absorption of oral medication
  • Subject is unable to swallow capsule
  • Subject with 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 the subject 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 starting the fedratinib treatment
  • Subject with a life expectancy of less than 6 months from the planned first dose of fedratinib.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

Japan21 sites

  • Local Institution - 002

    Aomori, 030-8553

  • Local Institution - 004

    Bunkyō City, 113-8677

  • Local Institution - 001

    Bunkyo-ku, Tokyo, 113-8431

  • Local Institution - 006

    Chūō, Yamanashi, 409-3898

  • Local Institution - 015

    Fukuoka, 812-8582

  • Local Institution - 018

    Hitachi, Ibaraki, 317-0077

  • Local Institution - 005

    Isehara City, Kanagawa, 259-1193

  • Local Institution - 010

    Kamogawa, 296-8602

  • Local Institution - 017

    Kitakyushu, 806-8501

  • Local Institution - 020

    Kumamoto, 8628655

  • Local Institution - 013

    Maebashi, 371-8511

  • Local Institution - 012

    Miyazaki, 889-1692

  • Local Institution - 009

    Nagasaki, 8528511

  • Local Institution - 016

    Osaka, 545-8586

  • Local Institution - 011

    Ōsaka-sayama, 589-8511

  • Local Institution - 014

    Sapporo, 003-0006

  • Local Institution - 007

    Shinagawa-ku, Tokyo, 141-8625

  • Local Institution - 008

    Shinjuku, 162-8666

  • Local Institution - 003

    Shinjyuku-ku, 160-0023

  • Local Institution - 021

    Suwa, Nagano, 392-8510

  • Local Institution - 019

    Takamatsu, 760-0017

Other trials in Japan

About this study

Official title: A Phase 1/2, Multicenter, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of Fedratinib in Japanese 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)

The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.

This is a Phase 1/2 multicenter, single arm, open-label study in Japanese subjects with DIPSS intermediate or high-risk PMF, post-PV or post-ET MF. The study consists of 2 parts: Phase 1 part to determine safety and tolerability and a RP2D. The Phase 1 portion of the study will explore one or more drug doses for fedratinib (300 mg and 400 mg) using a mTPI-2 design. Following completion of dose escalation and determination of MTD and/or a RP2D, the study will progress into the Phase 2 part to further evaluate the efficacy and safety.

The study will consist of 3 periods: a Screening Period, a Treatment Period including a 30-day follow-up after last dose visit and a survival follow-up period.

Being tested
Fedratinib
Keywords
Fedratinib, Myelofibrosis, Japanese
Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FedratinibDrug

    Also called BMS-847943

    Specified dose on specified days

Study groups in NCT04446650
Study groupRoleWhat they receive
Fedratinib AdministrationExperimentalThe fedratinib dose is 300 or 400 mg/day PO (3 or 4 x 100 mg capsules) to be self-administered orally once daily continuously on an outpatient basis, preferably together with food during an evening meal, the same time each day.
Receives: Drug: Fedratinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

    is the highest dose that causes DLTs in not more than 33% of the subjects treated with fedratinib in the first cycle with at least 3 evaluable subjects treated at this dose.

    Measured: Up to Cycle 1 (each cycle is 28 days)

  2. Recommended Phase 2 dose (RP2D)

    is a recommended Phase 2 dose that is determined as safe and tolerable by the Safety Review Committee based on the data from the first cycle with at least 3 evaluable subjects treated at each dose of the Phase 1 part.

    Measured: Up to Cycle 1 (each cycle is 28 days)

  3. Response Rate (RR)

    Proportion of subjects who have ≥ 35% SVR at end of Cycle 6 from baseline

    Measured: Up to Cycle 6 (each cycle is 28 days)

Secondary outcomes (14)

  1. Adverse Events (AEs)

    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

    Measured: From ICF signature up until 30 days after last dose of IP

  2. Pharmacokinetics - Cmax

    Peak (maximum) plasma concentration of the drug

    Measured: Up to Cycle 1 (each cycle is 28 days)

  3. Pharmacokinetics - AUC

    Area under the plasma concentration curve

    Measured: Up to Cycle 1 (each cycle is 28 days)

  4. Pharmacokinetics - Tmax

    Time to maximum plasma concentration

    Measured: Up to Cycle 1 (each cycle is 28 days)

  5. Symptom response rate (SRR)

    Proportion of subjects with ≥ 50% reduction in total symptom scores measured by MFSAF version 2.0 (Appendix C) at end of Cycle 6

    Measured: Up to Cycle 6 (each cycle is 28 days)

  6. Spleen volume response rate 25 (RR25)

    Proportion of subjects who have ≥ 25% reduction in spleen volume at the end of Cycle 6

    Measured: Up to Cycle 6 (each cycle is 28 days)

  7. Spleen Response Rate by Palpation (RRP)

    Proportion of subjects who have ≥ 50% reduction in spleen size by palpation at end of Cycle 6

    Measured: Up to Cycle 6 (each cycle is 28 days)

  8. Duration of spleen volume response (DR)

    Duration of ≥ 35% SVR by MRI/CT

    Measured: Up to 4 years

  9. Duration of spleen response by palpation (DRP)

    Time from the first documented palpable spleen response, according to the IWGMRT 2013 to the time of the first documented loss of response according to the IWG-MRT 2013.

    Measured: Up to 4 years

  10. Duration of symptoms response (DSR)

    Duration of ≥ 50% reduction in total symptom scores measured by MFSAF version 2.0

    Measured: Up to 4 years

  11. Spleen and Disease Progression Free Survival (SDPFS)

    Time from the start of fedratinib treatment to death due to any reason or disease progression (modified IWGMRT 2013 including ≥ 25% increase in spleen volume by MRI/CT)

    Measured: Up to 4 years

  12. Gastrointestinal adverse events

    Incidence of subjects with Grade 3 or higher Gastrointestinal events (nausea, diarrhea, or vomiting) according to CTCAE v5.0

    Measured: From ICF signature to the 30-day follow-up after last dose of IP

  13. Wernicke encephalopathy (WE) events

    Occurrence of confirmed Wernicke encephalopathy events

    Measured: From ICF signature to the 30-day follow-up after last dose of IP

  14. Overall Survival (OS)

    Time from the start of fedratinib treatment to death due to any reason

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2020
  2. Study start12 Oct 2020
  3. Primary completion5 Oct 2023
  4. Study completion30 Nov 2026 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04446650
Sponsor's protocol ID
FEDR-MF-003
Status last verified
Oct 2025
First submitted
16 Jun 2020
Last updated
21 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Fedratinib in people with Primary Myelofibrosis, run by Bristol-Myers Squibb at 21 sites in Japan.

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 22 inclusion and 42 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: under way, not looking for participants, as of the sponsor's last update on 21 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Japan. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Maximum Tolerated Dose (MTD) (time frame: Up to Cycle 1 (each cycle is 28 days)). The study lists 3 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 NCT04446650.

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 21 Oct 2025.

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