Clinical Trial TitleFedratinib in subjects with intermediate or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis and previously treated with ruxolitinib.
National Clinical Trial Number:NCT03755518
Clinical Trial Protocol Description:
Myelofibrosis (MF) belongs to a group of closely related blood cancers known as “myeloproliferative neoplasms” (MPNs) in which the bone marrow cells that produce the body’s blood cells develop and function abnormally. The result is excessive fibrous (scar) tissue formation in the bone marrow, which can lead to severe anemia, weakness, fatigue and enlarged spleen and liver. The cancer develops when a mutation occurs in the DNA of a single blood forming stem cell.
MF can occur on its own, called “primary myelofibrosis” or as a progression of other bone marrow diseases (called “post”). Other MPNs that can progress to myelofibrosis include polycythemia vera (PV) and essential thrombocythemia (ET). PV is a bone marrow disease that leads to an abnormal increase in the number of blood cells. The red blood cells are mostly affected. ET is a disease in which too many platelets are made in the blood and bone marrow. The characteristics of MF, post-PV-MF and post-ET-MF are virtually identical and treatment is generally the same for all three.
Between 50 and 60% of people with MF have a mutation of the Janus kinase 2 gene (JAK2). Mutant JAK2 tells blood cells to grow and divide even when the body is not asking for more blood cells. Treatment uses medicines to decrease the platelet count. In people with the JAK2 mutation, specific inhibitors of the JAK2 protein may be used, such as ruxolitinib. It works by blocking enzymes (JAK1 and JAK2) that cause scar tissue to form in the bone marrow. Ruxolitinib is currently the only approved therapy for MF.
However ruxolitinib can also cause risks of treatment-associated anemia and decreases in platelet cells that help blood clot (thrombocytopenia). The rate of discontinuation of ruxolitinib treatment at 1, 2, and 3 years is also high. For patients who have been previously treated with ruxolitinib and whose disease did not respond, there is no approved therapy and prognosis for these patients is poor. Fedratinib is an orally available inhibitor of JAK2 activity that inhibits JAK2 signaling.
The purpose of this study is to assess the effectiveness of fedratinib in successive 28-day cycles to treat subjects with intermediate or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis.
Clinical Trial Eligibility Criteria:
In order to participate you must meet the following criteria:
- Are 18 years of age or older.
- Have disease with a Dynamic International Prognostic Scoring System (DIPSS) Risk score of Intermediate or High.
- Have been treated previously with ruxolitinib.
- Are willing to follow the study visit schedule and other requirements.
You will be excluded from the study if any of the following criteria apply to you:
- Have had a splenectomy (removal of the spleen).
- Have had or plan to have a bone marrow transplant.
- Have a thiamine (vitamin B1) deficiency.
- Have received treatment with JAK inhibitor(s) other than ruxolitinib.
This is a partial list of inclusion and exclusion criteria.