Primary myelofibrosis, post-polycythemia vera myelofibrosis , or post-essential thrombocythemia myelofibrosis MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Fedratinib
Pharmaceutical Form: Capsule
INN or Proposed INN: fedratinib
Current Sponsor code: fedratinib
Other descriptive
Sponsors
Impact Biomedicines, Inc., a Wholly Owned Subsidiary of Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is at least 18 years of age at the time of signing the informed consent form (ICF) 2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Score (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-ET or post-PV myelofibrosis according to the IWG-MRT 2007 criteria, onfirmed by the most recent local pathology report 4. Subject has a DIPSS Risk score of Intermediate-2 or High 5. Subject has a measurable splenomegaly during the screening period as demonstrated by spleen volume of = 450 cm3 by MRI or CT-scan and by palpable spleen measuring = 5 cm below the left costal margin 6. Subject has a measurable total symptoms score (= 1) as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) 7. Subject has been previously exposed to ruxolitinib, and must meet at least one of the following criteria (a and/or b) a. Treatment with ruxolitinib for = 3 months with inadequate efficacy response (refractory) defined as < 10% spleen volume reduction by MRI or < 30% decrease from baseline in spleen size by palpation or regrowth (relapse) to these parameters following an initial response b. Treatment with ruxolitinib for = 28 days complicated by any of the following (intolerant): ? 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 8. Subject must have treatment-related toxicities from prior therapy resolved to Grade 1 or pretreatment baseline before start of last therapy prior to randomization 9. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted 10. Subject is willing and able to adhere to the study visit schedule and other protocol requirements 11. A female of childbearing potential (FCBP) must: a. Have 2 negative pregnancy tests as verified by the Investigator during screening prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study 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 study treatment (including dose interruptions), and for 30 days after discontinuation of study treatment. 12. 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 investigational product discontinuation, or longer if required for each compound and/or by local regulations, even if he has undergone a successful vasectomy. Are the trial s
Exclusion criteria
Exclusion criteria: 1. Any of the following laboratory abnormalities: a. Platelets 100 x 10^9/L d. Myeloblasts = 5 % in peripheral blood e. Estimated glomerular filtration rate 1.5 x upper limit of normal (ULN) 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 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 randomization 10. Subject has received ruxolitinib within 14 days prior to randomization 11. Subject with previous exposure to Janus kinase (JAK) inhibitor(s) other than ruxolitinib treatment 12. Subject on treatment with aspirin with doses > 150 mg daily 13. Subject with major surgery within 28 days prior to randomization 14. Subject with diagnosis of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemochromatosis, non-alcoholic steatohepatitis) 15. 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 randomization. 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 16. Subject with uncontrolled
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: From Screening to the end of Cycle 6;Main Objective: To evaluate the percentage of subjects with at least 35% spleen volume reduction in the fedratinib and the BAT arms.;Primary end point(s): Spleen volume response rate (RR); Secondary Objective: To evaluate myelofibrosis (MF)-associated symptoms as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) (Appendix B) To evaluate the percentage of subjects with at least 25% spleen volume reduction (SVR) To evaluate the safety of fedratinib To evaluate the reduction of spleen size by palpation To evaluate durability of spleen response by MRI/CT and by palpation To evaluate the durability of symptoms response To evaluate spleen and disease progression free survival To assess the effectiveness of the risk mitigation strategy for gastrointestinal events and Wernicke encephalopathy (WE) To evaluate Health-Related Quality of Life (HRQoL) as measured by the European Organization for Research and Treatment of Cancer Quality of Life C30 (EORTC QLQ-C30) (Appendix C) To evaluate Patient Reported Outcomes (PRO) as measured by the EQ-5D-5L questionnaire (Appendix D) To evaluate Overall Survival (OS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Symptom response rate (SRR) 2. Spleen volume response rate (RR25) ; Timepoint(s) of evaluation of this end point: 1. From C1D1 to the end of Cycle 6 2. From Screening to the end of Cycle 6 | — |
Countries
Australia, Austria, Belgium, China, Czech Republic, France, Germany, Hungary, Ireland, Italy, Korea, Republic of, Netherlands, Poland, Portugal, Russian Federation, Spain, United Kingdom
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed