What side effects are associated with this type of intervention?

Common treatments for Myelofibrosis include JAK inhibitors such as Ruxolitinib and Fedratinib. The known side effects of Ruxolitinib include anemia, thrombocytopenia, bruising, dizziness, and headaches. Fedratinib can cause gastrointestinal symptoms like nausea, vomiting, and diarrhea, as well as anemia and thrombocytopenia. Both drugs may also increase the risk of infections. BET inhibitors like BMS-986158, while still under investigation, may have side effects such as fatigue, gastrointestinal disturbances, and hematologic toxicities.

What prior FDA approvals exist?

The FDA has approved several treatments for Myelofibrosis, primarily focusing on JAK inhibitors. Ruxolitinib (Jakafi) and Fedratinib (Inrebic) are notable examples, both targeting the JAK-STAT pathway to manage symptoms and reduce spleen size. These treatments are relevant to the study of BMS-986158, which is being evaluated in combination with Ruxolitinib or Fedratinib. While BMS-986158 is a BET inhibitor, which represents a different mechanism of action, the combination with JAK inhibitors highlights the ongoing exploration of synergistic therapies in Myelofibrosis management.

What other types of research exist?

Promising novel alternatives to BMS-986158 for Myelofibrosis patients include JAK2 inhibitors such as Ruxolitinib and Fedratinib, which are already in use and have shown efficacy in clinical trials. Additionally, new therapies under investigation include BET inhibitors other than BMS-986158, and combination therapies involving JAK inhibitors with other agents like PI3K inhibitors or BCL2 inhibitors. These alternatives are being studied for their potential to improve outcomes in Myelofibrosis patients.

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BMS-986158 + Ruxolitinib/Fedratinib for Myelofibrosis

Phase 1 & 2

Waitlist Available

Research Sponsored by Bristol-Myers Squibb

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Treatment-related toxicities from prior therapy resolved to Grade 1 or pre-treatment baseline or determined to be irreversible prior to study treatment

Diagnosis of primary myelofibrosis (PMF), post-essential thrombocythemia (ET) or post-polycythemia vera (PV) myelofibrosis

Must not have

Women who are pregnant or breastfeeding at screening

Any significant acute or uncontrolled chronic medical illness

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 month and 12 month

Awards & highlights

Summary

This trial is testing a new drug called BMS-986158 for patients with high-risk blood cancer. It aims to see if the drug works better alone or when combined with existing treatments, Ruxolitinib and Fedratinib. Ruxolitinib is the first FDA-approved JAK inhibitor for myeloproliferative neoplasms, effective in controlling symptoms and improving splenomegaly, but many patients develop disease progression with long-term use.

Who is the study for?

This trial is for adults with a type of blood cancer called myelofibrosis, who are at intermediate or high risk. They must not have unresolved serious side effects from previous treatments and agree to use contraception if needed. Pregnant or breastfeeding women, those with acute illnesses or uncontrolled chronic conditions are excluded.

What is being tested?

The study tests the safety and effectiveness of BMS-986158 alone, and in combination with Ruxolitinib or Fedratinib. Participants will be divided into two parts: one part receiving combinations and the other receiving BMS-986158 alone to compare outcomes.

What are the potential side effects?

Potential side effects may include typical reactions related to cancer medications such as nausea, fatigue, liver issues, changes in blood counts leading to increased infection risk or bleeding problems. Specific side effect profiles will be monitored closely.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My side effects from previous treatments have mostly gone away or are stable.

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I have been diagnosed with a type of myelofibrosis.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant or breastfeeding.

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I do not have any severe or unmanaged chronic illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 month and 12 month

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 month and 12 month

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 month and 12 month for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

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

Side effects data

From 2021 Phase 1 & 2 trial • 83 Patients • NCT02419417

100%

Fatigue

75%

Nausea

75%

Decreased appetite

75%

Vomiting

50%

Thrombocytopenia

50%

Constipation

50%

Headache

50%

Dyspnoea

25%

Abdominal distension

25%

Pneumonia

25%

Hypokalaemia

25%

Cough

25%

Lymphocyte count decreased

25%

Abdominal discomfort

25%

Small intestinal obstruction

25%

Flank pain

25%

Abdominal pain

25%

Candida infection

25%

Muscle spasms

25%

Paraesthesia

25%

Dehydration

25%

Pain in extremity

25%

Pain in jaw

25%

Oropharyngeal pain

25%

Malignant neoplasm progression

25%

Diarrhoea

25%

Urinary tract infection

25%

Insomnia

25%

Weight decreased

25%

Dry mouth

25%

Dyspepsia

25%

Arthralgia

25%

Lacrimation increased

25%

Hot flush

25%

Back pain

25%

Early satiety

100%

80%

60%

40%

20%

Study treatment Arm

Part 1 Schedule A - BMS-986158 1.25 mg

Part 1 Schedule B - BMS-986158 3 mg

Part 1 Schedule A - BMS-986158 2 mg

Part 1 Schedule C - BMS-986158 3 mg

Part 1 Schedule B - BMS-986158 2 mg

Part 1 Schedule C - BMS-986158 2 mg

Part 1 Schedule A - BMS-986158 0.75 mg

Part 1 Schedule C - BMS-986158 4.5 mg

Part 1 Schedule A - BMS-986158 3 mg

Part 1 Schedule A - BMS-986158 4.5 mg

Part 2 Schedule A

Trial Design

7Treatment groups

Experimental Treatment

Group I: Part 2B2: BMS-986158 Mono and/or (BMS-986158 + Fedratinib), if applicableExperimental Treatment2 Interventions

Group II: Part 2B1: BMS-986158 + FedratinibExperimental Treatment2 Interventions

Group III: Part 2A3: BMS-986158 + RuxolitinibExperimental Treatment2 Interventions

Group IV: Part 2A2 Add-On: BMS-986158 + RuxolitinibExperimental Treatment2 Interventions

Group V: Part 2A1: BMS-986158 + RuxolitinibExperimental Treatment2 Interventions

Group VI: Part 1B: BMS-986158 + FedratinibExperimental Treatment2 Interventions

Group VII: Part 1A: BMS-986158 + RuxolitinibExperimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

BMS-986158

2015

Completed Phase 2

~90

Ruxolitinib

2018

Completed Phase 3

~1140

Fedratinib

2019

Completed Phase 1

~190

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Myelofibrosis include JAK inhibitors like Ruxolitinib and Fedratinib, and BET inhibitors such as BMS-986158. Ruxolitinib and Fedratinib work by inhibiting the Janus kinase (JAK) pathway, which is often overactive in Myelofibrosis, leading to reduced spleen size and symptom relief. BET inhibitors like BMS-986158 target bromodomain and extra-terminal (BET) proteins, which play a role in regulating gene expression. By inhibiting BET proteins, these drugs can potentially reduce the proliferation of malignant cells. These mechanisms are crucial for Myelofibrosis patients as they address the underlying disease processes, helping to manage symptoms and improve quality of life.