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)

NCT04446650 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: FEDR-MF-003
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 21

Brief 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. 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.

Conditions

Primary Myelofibrosis

Keywords

Fedratinib; Myelofibrosis; Japanese

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to Cycle 1 (each cycle is 28 days)

• 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.

  Up to Cycle 1 (each cycle is 28 days)

• Response Rate (RR)

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

  Up to Cycle 6 (each cycle is 28 days)

Secondary Outcomes (14)

• Adverse Events (AEs)

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

• Pharmacokinetics - Cmax

  Up to Cycle 1 (each cycle is 28 days)

• Pharmacokinetics - AUC

  Up to Cycle 1 (each cycle is 28 days)

• Pharmacokinetics - Tmax

  Up to Cycle 1 (each cycle is 28 days)

• Symptom response rate (SRR)

  Up to Cycle 6 (each cycle is 28 days)

Study Arms (1)

Fedratinib Administration

EXPERIMENTAL

The 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.

Drug: Fedratinib

Interventions

Fedratinib DRUG

Specified dose on specified days

Also known as: BMS-847943

Fedratinib Administration

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (21)

Local Institution - 021

Suwa, Nagano, 392-8510, Japan

Location

Local Institution - 001

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

Local Institution - 006

Chūō, Yamanashi, 409-3898, Japan

Location

Local Institution - 002

Aomori, 030-8553, Japan

Location

Local Institution - 004

Bunkyō City, 113-8677, Japan

Location

Local Institution - 015

Fukuoka, 812-8582, Japan

Location

Local Institution - 018

Hitachi, Ibaraki, 317-0077, Japan

Location

Local Institution - 005

Isehara City, Kanagawa, 259-1193, Japan

Location

Local Institution - 010

Kamogawa, 296-8602, Japan

Location

Local Institution - 017

Kitakyushu, 806-8501, Japan

Location

Local Institution - 020

Kumamoto, 8628655, Japan

Location

Local Institution - 013

Maebashi, 371-8511, Japan

Location

Local Institution - 012

Miyazaki, 889-1692, Japan

Location

Local Institution - 009

Nagasaki, 8528511, Japan

Location

Local Institution - 016

Osaka, 545-8586, Japan

Location

Local Institution - 011

Ōsaka-sayama, 589-8511, Japan

Location

Local Institution - 014

Sapporo, 003-0006, Japan

Location

Local Institution - 007

Shinagawa-ku, Tokyo, 141-8625, Japan

Location

Local Institution - 008

Shinjuku, 162-8666, Japan

Location

Local Institution - 003

Shinjyuku-ku, 160-0023, Japan

Location

Local Institution - 019

Takamatsu, 760-0017, Japan

Location

Related Links

• BMS Clinical Trial Information

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

fedratinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Bristol Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: June 25, 2020
• Study Start: October 12, 2020
• Primary Completion: October 5, 2023
• Study Completion (Estimated): November 30, 2026
• Last Updated: October 21, 2025

Record last verified: 2025-10

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

JP (21)