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).
- Conditions
- DIPSS-intermediate or high-risk PMF, post-PV MF, or post-ET MF
- Registration Number
- JPRN-jRCT2080225251
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 31
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is >= 20 years of age at the time of signing the informed consent form (ICF)
2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
3. Subject has diagnosis of Primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-essential thrombocythemia (post-ET) or post-polycythemia vera (post-PV) myelofibrosis (MF) according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2007 criteria, confirmed by the most recent local pathology report
4. Subject has a Dynamic International Prognostic Scoring System (DIPSS) Risk score of Intermediate-1 with symptom(s), Intermediate-2 or High
5. 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.
6. 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:
a. 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).
b. 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.
7. 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.
8. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
9. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
10. A female of childbearing potential (FCBP) must:
a. 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.
b. 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.
c. 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 postmenop
The presence of any of the following will exclude a subject from enrollment:
1. Any of the following laboratory abnormalities:
a. Platelets < 50 x 10^9/L (without platelet transfusion)
b. Absolute neutrophil count (ANC) < 1.0 x 10^9/L
c. White blood count (WBC) > 100 x 10^9/L
d. Myeloblasts >= 5 % in peripheral blood
e. Estimated creatinine clearance < 30 mL/min (as estimated by Cockcroft-Gault formula)
f. Serum amylase or lipase > 1.5 x upper limit of normal
g. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
h. 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.
2. Subject is pregnant or breastfeeding female.
3. Subject with previous splenectomy
4. Subject with previous or planned hematopoietic Stem-cell transplantation
5. Subject with prior history of Encephalopathy, including Wernicke encephalopathy (WE)
6. 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
7. 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
8. 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
9. 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.
10. Subject on treatment with myeloid growth factor (eg, granulocyte-colony stimulating factor [G-CSF]) within 14 days prior to starting the fedratinib treatment
11. Subject with previous exposure to JAK inhibitor(s) other than ruxolitinib treatment
12. Subject has received ruxolitinib within 14 days prior to starting the fedratinib treatment
13. Subject on treatment with aspirin with doses > 150 mg daily
14. Subject with major surgery within 28 days prior to starting the fedratinib treatment
15. Subject with diagnosis of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemochromatosis, non-alcoholic steatohepatitis)
16. 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
17. Subject with uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4)
18. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV)
a. Subject who are
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method