What side effects are associated with this type of intervention?

Common treatments for Myeloproliferative Disorders, such as ruxolitinib and fedratinib, often result in hematologic side effects like anemia and thrombocytopenia. For instance, ruxolitinib can cause grade ≥3 anemia in 38% of patients and thrombocytopenia in 22%. Non-hematologic side effects may include fatigue, nausea, and diarrhea. The investigational drug JNJ-88549968 is being studied for its safety and optimal dosing, with a focus on similar adverse events to ensure patient safety and treatment efficacy.

What prior FDA approvals exist?

Several drugs have been FDA-approved for the treatment of Myeloproliferative Disorders (MPNs). Ruxolitinib, a JAK1/2 inhibitor, is approved for myelofibrosis and polycythemia vera, targeting the JAK-STAT pathway, which is often dysregulated in MPNs. Fedratinib, another JAK2 inhibitor, is also approved for myelofibrosis. These treatments focus on managing symptoms and reducing spleen size. While JNJ-88549968 is being studied specifically for CALR-mutated MPNs, the general approach of targeting specific molecular pathways is consistent with these prior FDA-approved therapies.

What other types of research exist?

Promising alternatives to JNJ-88549968 for Myeloproliferative Disorder patients include ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, which has shown efficacy in polycythemia vera and myelofibrosis. Additionally, bosutinib, a tyrosine kinase inhibitor, has been evaluated for chronic myeloid leukemia and may offer potential benefits. Both drugs have been studied extensively for safety and efficacy, making them viable options for consideration in 2024.

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Monoclonal Antibodies

JNJ-88549968 for Myeloproliferative Disorder

Q: What is the mechanism of action of this treatment?

Common treatments for Myeloproliferative Disorders (MPNs) include JAK inhibitors (e.g., ruxolitinib), interferons, and hydroxyurea. JAK inhibitors work by blocking the Janus kinase pathway, which is often overactive in MPNs due to mutations like JAK2 V617F, thereby reducing abnormal cell proliferation and alleviating symptoms. Interferons modulate the immune system to target malignant cells, while hydroxyurea inhibits DNA synthesis, reducing the production of abnormal blood cells. These treatments are crucial for MPN patients as they help manage symptoms, reduce the risk of complications like thrombosis, and potentially slow disease progression. The study of JNJ-88549968, which aims to determine its safety and optimal dosing, is important as it may offer a new targeted therapy option, potentially improving patient outcomes by providing a more effective or better-tolerated treatment.

Phase 1

Recruiting

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

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

Must have

Be greater than or equal to (>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent

Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, JNJ-88549968, to find the safest and most effective dose for patients. It aims to determine the best dosing schedule and ensure the drug's safety.

Who is the study for?

This trial is for adults with a specific mutation called CALR in their blood cells, leading to conditions like thrombocytosis and myelofibrosis. They should be able to perform daily activities with ease or only have slight limitations (ECOG <=2). The study excludes details not provided.

What is being tested?

The trial tests JNJ-88549968's safety and the best dose for treating certain blood disorders. It has two parts: finding the right dose (Dose Escalation) and then seeing how safe it is at that dose (Cohort Expansion).

What are the potential side effects?

Specific side effects of JNJ-88549968 are not listed, but generally, such treatments may cause fatigue, nausea, bruising or bleeding risks, liver issues, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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I am at least 18 years old or the legal age of majority where the study is conducted.

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My blood disorder is due to a specific CALR mutation.

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I can take care of myself and am up and about more than half of my waking hours.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Part 1 and 2: Number of Participants with Adverse Events (AEs)

Part 1 and 2: Number of Participants with Adverse Events (AEs) by Severity

Part 1: Number of Participants With Dose Limiting Toxicity (DLT)

Secondary study objectives

Part 1 and 2: Complete Response (CR) Rate

Part 1 and 2: Duration of Response (DOR)

Part 1 and 2: Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968

+4 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Dose Escalation (Part 1) and Dose Expansion (Part 2)Experimental Treatment1 Intervention

In dose escalation (Part 1), participants will receive JNJ-88549968. The dose will be escalated sequentially to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule(s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens. In dose expansion (Part 2), participants will receive JNJ-88549968 at the RP2D regimen(s) determined in dose escalation (Part 1).

0 / 3Eligibility 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 Myeloproliferative Disorders (MPNs) include JAK inhibitors (e.g., ruxolitinib), interferons, and hydroxyurea. JAK inhibitors work by blocking the Janus kinase pathway, which is often overactive in MPNs due to mutations like JAK2 V617F, thereby reducing abnormal cell proliferation and alleviating symptoms. Interferons modulate the immune system to target malignant cells, while hydroxyurea inhibits DNA synthesis, reducing the production of abnormal blood cells. These treatments are crucial for MPN patients as they help manage symptoms, reduce the risk of complications like thrombosis, and potentially slow disease progression. The study of JNJ-88549968, which aims to determine its safety and optimal dosing, is important as it may offer a new targeted therapy option, potentially improving patient outcomes by providing a more effective or better-tolerated treatment.

Targeted therapy of polycytemia vera patients.Incidence, Survival and Prevalence Statistics of Classical Myeloproliferative Neoplasm in Korea.Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT).