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)
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|ClinicalTrials.gov Identifier: NCT04446650|
Recruitment Status : Recruiting
First Posted : June 25, 2020
Last Update Posted : February 18, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Primary Myelofibrosis||Drug: Fedratinib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||October 12, 2020|
|Estimated Primary Completion Date :||November 5, 2022|
|Estimated Study Completion Date :||December 31, 2024|
Experimental: Fedratinib Administration
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.
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to Cycle 1 (each cycle is 28 days) ]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.
- Recommended Phase 2 dose (RP2D) [ Time Frame: Up to Cycle 1 (each cycle is 28 days) ]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.
- Response Rate (RR) [ Time Frame: Up to Cycle 6 (each cycle is 28 days) ]Proportion of subjects who have ≥ 35% SVR at end of Cycle 6 from baseline
- Adverse Events (AEs) [ Time Frame: From ICF signature up until 30 days after last dose of IP ]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.
- Pharmacokinetics - Cmax [ Time Frame: Up to Cycle 1 (each cycle is 28 days) ]Peak (maximum) plasma concentration of the drug
- Pharmacokinetics - AUC [ Time Frame: Up to Cycle 1 (each cycle is 28 days) ]Area under the plasma concentration curve
- Pharmacokinetics - Tmax [ Time Frame: Up to Cycle 1 (each cycle is 28 days) ]Time to maximum plasma concentration
- Symptom response rate (SRR) [ Time Frame: Up to Cycle 6 (each cycle is 28 days) ]Proportion of subjects with ≥ 50% reduction in total symptom scores measured by MFSAF version 2.0 (Appendix C) at end of Cycle 6
- Spleen volume response rate 25 (RR25) [ Time Frame: Up to Cycle 6 (each cycle is 28 days) ]Proportion of subjects who have ≥ 25% reduction in spleen volume at the end of Cycle 6
- Spleen Response Rate by Palpation (RRP) [ Time Frame: Up to Cycle 6 (each cycle is 28 days) ]Proportion of subjects who have ≥ 50% reduction in spleen size by palpation at end of Cycle 6
- Duration of spleen volume response (DR) [ Time Frame: Up to 4 years ]Duration of ≥ 35% SVR by MRI/CT
- Duration of spleen response by palpation (DRP) [ Time Frame: Up to 4 years ]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.
- Duration of symptoms response (DSR) [ Time Frame: Up to 4 years ]Duration of ≥ 50% reduction in total symptom scores measured by MFSAF version 2.0
- Spleen and Disease Progression Free Survival (SDPFS) [ Time Frame: Up to 4 years ]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)
- Gastrointestinal adverse events [ Time Frame: From ICF signature to the 30-day follow-up after last dose of IP ]Incidence of subjects with Grade 3 or higher Gastrointestinal events (nausea, diarrhea, or vomiting) according to CTCAE v5.0
- Wernicke encephalopathy (WE) events [ Time Frame: From ICF signature to the 30-day follow-up after last dose of IP ]Occurrence of confirmed Wernicke encephalopathy events
- Overall Survival (OS) [ Time Frame: Up to 4 years ]Time from the start of fedratinib treatment to death due to any reason
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04446650
|Contact: Associate Director Clinical Trial Disclosurefirstname.lastname@example.org|
|Aomori Prefectural Central Hospital||Recruiting|
|Aomori, Japan, 030-8553|
|Juntendo University Hospital||Recruiting|
|Bunkyo-ku, Japan, 113-8431|
|Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital||Recruiting|
|Bunkyo-ku, Japan, 113-8677|
|University of Yamanashi Hospital||Recruiting|
|Chuo, Japan, 409-3898|
|Kyushu University Hospital||Recruiting|
|Fukuoka, Japan, 812-8582|
|Tokai University Hospital||Recruiting|
|Isehara City, Kanagawa, Japan, 259-1193|
|Kameda General Hospital||Recruiting|
|Kamogawa, Japan, 296-8602|
|Gunma University Hospital||Not yet recruiting|
|Maebashi, Japan, 371-8511|
|University of Miyazaki Hospital||Not yet recruiting|
|Miyazaki, Japan, 889-1692|
|Japanese Red Cross Nagasaki Genbaku Hospital||Recruiting|
|Nagasaki-shi, Japan, 8528511|
|Kindai University Hospital||Not yet recruiting|
|Osaka-Sayama, Japan, 589-8511|
|Osaka City University Hospital||Recruiting|
|Osaka, Japan, 545-8586|
|Sapporo Hokuyu Hospital||Not yet recruiting|
|Sapporo, Japan, 003-0006|
|NTT Medical Center Tokyo||Recruiting|
|Shinagawa-ku, Tokyo, Japan, 141-8625|
|Tokyo Women's Medical University Hospital||Not yet recruiting|
|Shinjuku City, Japan, 162-8666|
|Tokyo Medical University Hospital||Recruiting|
|Shinjyuku-ku, Japan, 160-0023|
|Study Director:||Kiyoshi Okazuka, MD||Celgene|