This trial is evaluating whether BMS-986158 will improve 5 primary outcomes and 13 secondary outcomes in patients with Primary Myelofibrosis. Measurement will happen over the course of Up to 56 days.
This trial requires 192 total participants across 7 different treatment groups
This trial involves 7 different treatments. BMS-986158 is the primary treatment being studied. Participants will be divided into 7 treatment groups. There is no placebo group. The treatments being tested are in Phase 1 & 2 and have already been tested with other people.
Most of the disease is thought to be the result of genetic mutations and/or environmental factors, some of which may be modifiable. Genetic and environmental factors do not seem to be directly linked in PPMF. Further study is needed to pinpoint the causative factors.
A substantial population may achieve primary M. myelofibrosis "cure" by obtaining sustained deep hematologic and molecular responses and prolonging survival and maintaining low to normal WBC counts.
Although the true incidence of primary myelofibrosis per person per year is unknown, the incidence of primary myelofibrosis appears to reach a maximum at or close to adulthood.
Most patients are satisfied with their treatment and their doctor's response. Most patients prefer to be treated in specialty centers rather than a general practitioner. There is a large variation in patients' preferences, but most would still opt to see a general practitioner if one were available. Patients receiving a bone marrow or blood sample would not necessarily be going to a specialist.
PPMF is a rare blood-cancer affecting the bone marrow and a group of patients are at risk of having an early post-natal diagnosis. It is a myeloproliferative disorder with a rapid progression to myelofibrosis or acute leukemia. The hallmark, in PPMF, is, besides a characteristic constellation of dysplasia, a progressive marrow fibrosis, as well as the myeloperoxidase assay, which is helpful for the diagnosis of PPMF.
Almost all patients with PMF have a tendency to thrombosis. This tendency is stronger in young and middle aged patients, and may be more pronounced in patients with JAK2(V617F) mutation.
There still are few new treatments for patients with newly developing myelofibrosis because few new drug therapies that could prolong response to existing therapies have been approved for this disease.
The inheritance of HSC disease and the hematological phenotype of patients with PMF and related conditions do not show a clear pattern of inheritance by family history.
The most common side effects were nausea, fatigue, myalgia, back pain, and dizziness. It was determined that BMS-986158 was well tolerated and recommended a dose increase of bms-986158 that ranged between 20 and 120 mg per day. The next dose increment would be at doses of 90 mg, 120 mg, 80 mg and 45 mg. Each increment was determined to be well tolerated. BMS-986158 was not found to be the cause of any life-threatening side effects.
The data presented here indicate that some of the patients previously treated with Bms-986158 may no longer be candidates for this agent. Further, the presence of an AML at diagnosis strongly predicts a poor prognosis in patients treated with Bms-986158, suggesting that Bms-986158 does not help treat MDS patients with AML.
The clinical and biological effect of this candidate bm-986158 (2,6-diamino-4-phenyl-1H-pyrazolo [3,4-d] pyridin-3-one) molecule has been evaluated in vitro and in vivo. In vitro, it was proven to be not cytotoxic up to 100 μM. By intracellular and extracellular uptake we demonstrated an effective uptake of 2,6-diamino-4-phenyl-1H-pyrazolo [3,4-d] pyridin-3-one into cells and their nuclei, respectively.
The average age of incidence of the disorder is 55 to 59 years. The mean age of diagnosis of the disease has increased from 53.6 years in the 1960s to 70.5 years today. It is estimated that the number of new cases of primary myelofibrosis per year in the United States is 2 to 4 per 100,000 population, with the incidence (the number diagnosed with the disorder each year) per 100,000 population inversely proportional to the age of diagnosis. The mean age of onset of the disease in Europe is 60 years, and the average age of diagnosis is 59 years. In addition, it is estimated that there are 3 to 4 new cases per 100,000 population a year in Europe.