What side effects are associated with this type of intervention?

Common treatments for Myeloproliferative Neoplasms (MPNs) include targeted therapies such as ruxolitinib and fedratinib, as well as other agents like hydroxyurea and interferon-alpha. Ruxolitinib and fedratinib, both JAK inhibitors, can cause side effects such as thrombocytopenia, anemia, and gastrointestinal disturbances. Hydroxyurea may lead to cytopenias, mucocutaneous ulcers, and potential teratogenicity. Interferon-alpha can cause flu-like symptoms, fatigue, and long-term use may increase the risk of second malignancies. These side effects are important considerations when evaluating the safety and tolerability of novel agents like INCA033989.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Myeloproliferative Neoplasms (MPNs). Notably, ruxolitinib and fedratinib, both JAK inhibitors, have been approved for the treatment of myelofibrosis, a type of MPN. Ruxolitinib has demonstrated significant efficacy in reducing spleen volume and alleviating symptoms in patients with primary and secondary myelofibrosis. Similarly, fedratinib has been effective in patients who are resistant or intolerant to ruxolitinib. These therapies work by inhibiting the JAK-STAT pathway, which is often dysregulated in MPNs, thereby modulating abnormal blood cell proliferation.

What other types of research exist?

Promising novel alternatives to INCA033989 for Myeloproliferative Neoplasms patients include: 1) Fedratinib, a JAK2 inhibitor, which has shown efficacy in patients with myelofibrosis previously treated with ruxolitinib. 2) Imetelstat, a telomerase inhibitor, which is being evaluated in clinical trials for myelofibrosis. 3) Pegylated interferon alfa-2a, which has demonstrated high rates of hematologic and molecular response in patients with polycythemia vera and essential thrombocythemia. These alternatives offer potential benefits and should be discussed with a healthcare provider to determine the best treatment option.

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INCA033989 for Myeloproliferative Disorder (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

Existing documentation from a qualified local laboratory of CALR exon-9 mutation.

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years and 60 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called INCA033989 in patients with a type of blood cancer. The goal is to find the safest and most effective dose by checking for side effects and how well the drug works.

Who is the study for?

This trial is for people who have been diagnosed with myeloproliferative neoplasms, specifically Myelofibrosis (MF) or Essential Thrombocythemia (ET), and are expected to live more than 6 months. They must be willing to undergo bone marrow biopsies and have a documented CALR exon-9 mutation.

What is being tested?

The study tests INCA033989's safety and tolerability in patients with myeloproliferative disorders. It aims to find the highest dose patients can take without serious side effects (MTD) and suggest doses for future studies.

What are the potential side effects?

Possible side effects of INCA033989 include reactions at the drug administration site, fatigue, changes in blood counts, gastrointestinal symptoms, liver enzyme alterations, and potential allergic responses.

Eligibility Criteria

Inclusion Criteria

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

Select...

My tests show a CALR exon-9 mutation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years and 60 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years and 60 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years and 60 days 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 participants with Dose Limiting Toxicities (DLTs)

Number of participants with TEAEs leading to dose modification or discontinuation

Number of participants with Treatment-emergent Adverse Events (TEAEs)

Secondary study objectives

Mean change in disease-related allele burden

Participants With ET: Mean change from baseline of total symptom score (TSS)

Participants With ET: Response Rate

+11 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Part 1b: Dose Expansion - with MFExperimental Treatment1 Intervention

INCA033989 will be administered at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.

Group II: Part 1b: Dose Expansion - with ETExperimental Treatment1 Intervention

INCA033989 will be administered at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.

Group III: Part 1a Dose Escalation Cohort Disease Group A - with MFExperimental Treatment1 Intervention

INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) will enroll in this group.

Group IV: Part 1a Dose Escalation Cohort Disease Group A - with ETExperimental Treatment1 Intervention

0 / 1Eligibility 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 Myeloproliferative Neoplasms (MPNs) include targeted therapies like JAK inhibitors (e.g., ruxolitinib and fedratinib) and novel agents that modulate blood cell proliferation. JAK inhibitors work by blocking the Janus kinase (JAK) pathway, which is often overactive in MPNs, leading to uncontrolled cell growth. By inhibiting this pathway, these drugs help reduce symptoms such as splenomegaly and improve overall quality of life. Novel agents like INCA033989, currently under study, aim to further refine this approach by targeting specific molecular mechanisms involved in MPNs. These treatments are vital for MPN patients as they offer more precise control over disease progression and symptom management, potentially leading to better outcomes and fewer side effects compared to traditional therapies.

Recent advances in diagnosis and treatment of chronic myeloproliferative neoplasms.