BMS-986158 for Primary Myelofibrosis

Phase-Based Estimates
1
Effectiveness
1
Safety
Local Institution, Wollongong, Australia
Primary Myelofibrosis+1 More
BMS-986158 - Drug
Eligibility
18+
All Sexes
Eligible conditions
Primary Myelofibrosis

Study Summary

This study is evaluating whether a drug called BMS-986158 can be used to treat blood cancers.

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Eligible Conditions

  • Primary Myelofibrosis
  • Agnogenic Myeloid Metaplasia

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Compared to trials

Study Objectives

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.

Month 12
Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: SDPFS rates at 6 months and 12 months
Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: median SDPFS at 6 months and 12 months
Up to 168 days
Additional measures based on TSS measured by MFSAF
Response rate defined as proportion of participants with SVR ≥ 35% by MRI (preferred) or CT (if MRI is contraindicated) assessed by BICR
Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR)
Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF)
Up to 24 months
For transfusion dependent (TD), proportion of participants becoming TI as measured by the absence of red blood cell (RBC) transfusions over any consecutive 12-week period
For transfusion dependent (TD), proportion of participants becoming Tl as measured by the absence of erythropoiesis stimulating agents (ESA) over any consecutive 12-week period
For transfusion dependent (TD), proportion of participants becoming Tl as measured by the absence of hydroxyurea over any consecutive 12-week period
For transfusion independent (TI), proportion of participants having ≥ 2.0 g/dL hemoglobin (Hgb) increase over baseline
Up to 26 months
Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria
Up to 52 months
Incidence of AEs leading to discontinuation
Incidence of adverse events (AEs)
Incidence of death
Incidence of serious adverse events (SAEs)
Up to 56 days
Summary of PK parameters: area under the concentration-time curve from time zero to the time of the last quantifiable concentration ((AUC (0-T))
Summary of PK parameters: time of maximum observed concentration (Tmax)
Summary of pharmacokinetics (PK) parameters: maximum observed concentration (Cmax)

Trial Safety

Safety Estimate

1 of 3

Compared to trials

Trial Design

7 Treatment Groups

No Control Group
Part 2B2: BMS-986158 Mono and/or (BMS-986158 + Fedratinib), if applicable

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.

Part 2B2: BMS-986158 Mono and/or (BMS-986158 + Fedratinib), if applicable
Part 2A2 Add-On: BMS-986158 + Ruxolitinib
Part 2A: BMS-986158 + Ruxolitinib
Part 2B1: BMS-986158 + Fedratinib
Part 1B: BMS-986158 + Fedratinib
Part 1A: BMS-986158 + Ruxolitinib
Part 2A1: BMS-986158 + Ruxolitinib
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Fedratinib
FDA approved
Ruxolitinib
FDA approved
BMS-986158
Not yet FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: 6 month and 12 month
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly 6 month and 12 month for reporting.

Closest Location

Local Institution - San Diego, CA

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. There are 3 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Diagnosis of primary myelofibrosis (PMF), post-essential thrombocythemia (ET) or post-polycythemia vera (PV) myelofibrosis
Treatment-related toxicities from prior therapy resolved to Grade 1 or pre-treatment baseline or determined to be irreversible prior to study treatment
Must agree to follow specific methods of contraception, if applicable

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What causes primary myelofibrosis?

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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.

Unverified Answer

Can primary myelofibrosis be cured?

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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.

Unverified Answer

How many people get primary myelofibrosis a year in the United States?

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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.

Unverified Answer

What are common treatments for primary myelofibrosis?

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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.

Unverified Answer

What is primary myelofibrosis?

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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.

Unverified Answer

What are the signs of primary myelofibrosis?

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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.

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Have there been any new discoveries for treating primary myelofibrosis?

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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.

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Does primary myelofibrosis run in families?

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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.

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What are the common side effects of bms-986158?

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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.

Unverified Answer

What does bms-986158 usually treat?

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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.

Unverified Answer

What are the latest developments in bms-986158 for therapeutic use?

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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.

Unverified Answer

What is the average age someone gets primary myelofibrosis?

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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.

Unverified Answer
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