What side effects are associated with this type of intervention?

Common treatments for Myeloproliferative Neoplasms (MPNs) include ruxolitinib, interferon, and hydroxyurea. Ruxolitinib, a JAK1/2 inhibitor, can cause cytopenias, dizziness, headache, fatigue, bruising, elevated serum cholesterol, and increased risk of infections. Interferon therapy may lead to flu-like symptoms, fatigue, depression, and cytopenias. Hydroxyurea is associated with myelosuppression, gastrointestinal disturbances, and potential long-term risk of leukemic transformation. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Myeloproliferative Neoplasms (MPNs). Ruxolitinib, a JAK1/2 inhibitor, is approved for myelofibrosis and polycythemia vera, providing symptom relief and spleen size reduction. Fedratinib, another JAK2 inhibitor, is also approved for myelofibrosis, particularly in patients who are resistant or intolerant to ruxolitinib. Additionally, interferon-alpha has been used off-label for MPNs, particularly in polycythemia vera and essential thrombocythemia, due to its ability to induce hematologic and molecular responses.

What other types of research exist?

Promising novel alternatives to INCA033989 for Myeloproliferative Neoplasms patients in 2024 include: 1) Ruxolitinib, a JAK1/2 inhibitor, which is already used in combination therapies. 2) Momelotinib, another JAK inhibitor, which has shown efficacy in clinical trials for myelofibrosis. 3) Pegylated interferon alfa-2a, which has demonstrated high rates of hematologic and molecular response in polycythemia vera and essential thrombocythemia.

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Monoclonal Antibodies

INCA033989 + Ruxolitinib 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

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, alone or with ruxolitinib, in patients with a type of blood cancer. The goal is to find the safest dose and see how well patients can tolerate it. Ruxolitinib is a medication used to treat myelofibrosis.

Who is the study for?

This trial is for people with myeloproliferative neoplasms who have a life expectancy over 6 months and measurable disease. They must be in good enough health to perform daily activities (ECOG score of 0-2) and willing to undergo bone marrow procedures. Participants should not have other active cancers, significant heart issues, or certain infections like HIV.

What is being tested?

The study tests INCA033989 alone or combined with Ruxolitinib to find the safest and most effective doses for treating myeloproliferative neoplasms. It aims to identify any dose-related toxicities and establish recommended dosages for further research.

What are the potential side effects?

While specific side effects are not listed here, common ones may include fatigue, digestive problems, blood count changes, potential liver function alterations, and reactions at the infusion site. The severity can range from mild discomforts to more serious complications.

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

7Treatment groups

Experimental Treatment

Group I: Part 1c: Dose ExpansionExperimental Treatment2 Interventions

INCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with Ruxolitinib. Participants with myelofibrosis (MF) will enroll in this group. The participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks.

Group II: Part 1b: Dose Expansion - with TGB-MF SubOpt RExperimental Treatment2 Interventions

INCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group.

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

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

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

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

Group V: Part 1a: Dose Escalation Cohort Disease Group B - with TGB-MF SubOpt RExperimental Treatment2 Interventions

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

Group VI: 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 as monotherapy 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 VII: Part 1a Dose Escalation Cohort Disease Group A - with ETExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ruxolitinib

2018

Completed Phase 3

~1170

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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 Myeloproliferative Neoplasms (MPNs) include JAK inhibitors like ruxolitinib, which block the overactive JAK-STAT signaling pathway to reduce abnormal blood cell proliferation. Hydroxyurea inhibits DNA synthesis, thereby controlling cell growth, while interferon-alpha modulates the immune system to target malignant cells. These mechanisms are vital for MPN patients as they help manage symptoms, reduce the risk of complications such as thrombosis, and potentially slow disease progression.