What side effects are associated with this type of intervention?

Common treatments for Myelofibrosis, including BET inhibitors like INCB057643, often have side effects such as thrombocytopenia, anemia, and gastrointestinal disturbances. BET inhibitors specifically can also cause inhibition of erythroid, granulocytic, and lymphoid cell differentiation, leading to broader hematologic toxicities. Other treatments, such as JAK2 inhibitors, may result in side effects like cytopenias, infections, and elevated liver enzymes. Patients may also experience fatigue, headaches, and dizziness. It is crucial to monitor these side effects closely and manage them in collaboration with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments for Myelofibrosis, including JAK2 inhibitors like ruxolitinib and fedratinib, which target the Janus kinase pathway involved in the disease's pathogenesis. These treatments help reduce spleen size and alleviate symptoms. While specific FDA approvals for BET inhibitors in Myelofibrosis are not detailed, ongoing studies like the trial of INCB057643 suggest a growing interest in exploring gene expression modulation as a therapeutic strategy. Other treatments include hydroxyurea and interferon-alpha, which are used to manage symptoms and control blood counts.

What other types of research exist?

Promising alternatives to INCB057643 for Myelofibrosis patients include ruxolitinib, a JAK1/2 inhibitor, which has shown efficacy in treating myeloproliferative disorders. Additionally, TG101348 (fedratinib), another JAK2 inhibitor, has demonstrated therapeutic efficacy in preclinical models. These inhibitors target the JAK-STAT pathway, which is crucial in the pathogenesis of myelofibrosis.

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INCB057643 +/- Ruxolitinib for Myelofibrosis (LIMBER Trial)

Phase 1

Recruiting

Research Sponsored by Incyte Corporation

Eligibility Criteria Checklist

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

Must have

- Primary MF or secondary MFs (post-PV MF, post-ET MF), histologically or cytologically confirmed according to WHO 2016 criteria.

- Primary MF or secondary MFs (post-PV MF, post-ET MF), histologically or cytologically confirmed according to WHO 2016 criteria with measurable disease and risk category of intermediate-2 or high according to DIPSS.

Must not have

Prior receipt of a BET inhibitor within 5 half-lives of the compound, and/or experienced BET inhibitor-related AE(s) resulting in dose discontinuation.

Participants who have received allogeneic hematopoietic stem cell transplantation within 6 months of enrollment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 9 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called INCB057643, alone or with ruxolitinib, for patients with certain blood cancers like myelofibrosis. The goal is to see if it can stop cancer growth or help other treatments work better. Ruxolitinib has been approved for the treatment of myelofibrosis and has shown clinical benefits in reducing symptoms and improving survival.

Who is the study for?

This trial is for adults with myelofibrosis or other advanced myeloid neoplasms who have tried at least one treatment without success. They must not be candidates for a stem-cell transplant and agree to prevent pregnancy. A palpable spleen of certain size and specific disease risk categories are required.

What is being tested?

The study tests the safety and potential effectiveness of INCB057643 alone or combined with ruxolitinib in treating myelofibrosis and related conditions. Participants will either receive this new treatment option or continue their current dose of ruxolitinib if already on it.

What are the potential side effects?

Possible side effects include reactions similar to those experienced with other cancer treatments, such as fatigue, digestive issues, blood disorders, increased infection risk, and any unique effects related to BET inhibitors which were previously intolerable.

Eligibility Criteria

Inclusion Criteria

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

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My condition is confirmed as primary or secondary myelofibrosis according to WHO 2016.

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My condition is a type of myelofibrosis, confirmed by tests and considered high-risk.

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I am 18 years old or older.

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I am not eligible for treatments that could potentially cure my condition, like stem-cell transplantation.

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My MDS is classified from very low to high risk according to IPSS-R.

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I do not have juvenile myelomonocytic leukemia.

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My condition is a relapse or resistant to treatment for myelofibrosis, MDS, or MDS/MPN.

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My condition is a type of blood cancer classified as MDS/MPN according to WHO 2016.

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My condition is a type of blood cancer that has returned or didn't respond to treatment.

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My spleen is enlarged and can be felt more than 10 cm below my rib cage.

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I have myelofibrosis and have been treated with a JAK inhibitor.

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I am not eligible for treatments that could potentially cure my condition, like stem-cell transplantation.

Exclusion Criteria

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

Select...

I have previously taken a BET inhibitor and stopped due to side effects.

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I had a stem cell transplant from a donor within the last 6 months.

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I am not on any other cancer treatments.

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I have an active hepatitis B or C infection, or I'm at risk for hepatitis B reactivation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 9 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 9 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 9 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Number of treatment-emergent adverse events

Secondary study objectives

Anemia Response (MF only)

BM Blast Partial Remission (MF, MDS, and MDS/MPN)

Bone Marrow (BM) Blast Complete Remission (MF, myelodysplastic syndrome (MDS), and MDS/myeloproliferative neoplasm (MPN))

+11 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Part 2 : INCB057643 Combination with RuxolitinibExperimental Treatment2 Interventions

Combination arm in dose escalation and dose expansion

Group II: Part 1 : INCB057643 MonotherapyExperimental Treatment1 Intervention

INCB057643 dose escalation and dose expansion

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ruxolitinib

2018

Completed Phase 3

~1170

0 / 16Eligibility 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

The most common treatments for Myelofibrosis (MF) include JAK2 inhibitors and BET inhibitors. JAK2 inhibitors, such as ruxolitinib, target the Janus kinase 2 enzyme, which is often mutated in MF, leading to excessive cell proliferation and inflammation. By inhibiting this pathway, JAK2 inhibitors can reduce symptoms, decrease spleen size, and improve quality of life. BET inhibitors, like INCB057643, work by inhibiting bromodomain and extra-terminal domain proteins that regulate gene expression. This modulation can reduce the proliferation of malignant cells by affecting genes involved in cell cycle regulation and apoptosis. These treatments are crucial for MF patients as they help manage symptoms, reduce disease burden, and potentially improve survival outcomes.