What side effects are associated with this type of intervention?

Common treatments for Primary Myelofibrosis (PMF) include tyrosine kinase inhibitors (TKIs) such as ruxolitinib and fedratinib. Ruxolitinib can cause side effects like anemia, thrombocytopenia, and increased risk of infections. Fedratinib may lead to gastrointestinal symptoms, anemia, elevated liver enzymes, and in rare cases, encephalopathy. Hydroxyurea, another treatment option, can cause cytopenias, mucocutaneous ulcers, and potential teratogenicity. Interferon-alpha is associated with flu-like symptoms, fatigue, and depression. These side effects should be carefully managed under the guidance of a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several Tyrosine Kinase Inhibitors (TKIs) for the treatment of Primary Myelofibrosis (PMF). Ruxolitinib, a JAK1/JAK2 inhibitor, was the first TKI approved for PMF and has shown efficacy in reducing spleen size and alleviating symptoms. Fedratinib, another JAK2 inhibitor, was later approved for patients with PMF, particularly those who are resistant or intolerant to Ruxolitinib. Both drugs have significantly improved the management of PMF by targeting the JAK-STAT pathway, which is often dysregulated in this condition.

What other types of research exist?

Promising novel alternatives to TL-895 for Primary Myelofibrosis patients include Ruxolitinib, which has shown efficacy in multiple studies, and Dasatinib, which has demonstrated substantial improvements in blood counts and quality of life in related myeloid disorders. Additionally, ongoing research into other JAK2 inhibitors and multi-tyrosine kinase inhibitors may provide further options.

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Tyrosine Kinase Inhibitor

TL-895 + Ruxolitinib for Myelofibrosis

Phase 1 & 2

Recruiting

Research Sponsored by Telios Pharma, Inc.

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS)

Must not have

Treatment-naive subjects: Prior treatment with any JAKi

Subjects with suboptimal response to ruxolitinib: Documented disease progression while on ruxolitinib treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 48 month

Awards & highlights

Summary

This trial tests TL-895, a new oral medication, for treating Myelofibrosis, a type of bone marrow cancer. It targets patients who haven't tried certain treatments or didn't respond well to previous medications. TL-895 works by blocking enzymes that help cancer cells grow.

Who is the study for?

This trial is for adults with Myelofibrosis (MF) who are either new to JAK inhibitor treatments or haven't responded well to Ruxolitinib. They should have a confirmed MF diagnosis, a spleen enlarged by at least 5 cm or of a certain volume, and be in fair health as judged by their ability to perform daily activities.

What is being tested?

The study tests TL-895 combined with Ruxolitinib on two groups: those who've never had JAK inhibitors and those whose condition didn't improve enough with just Ruxolitinib. It aims to see if this combination can better manage symptoms of MF.

What are the potential side effects?

Potential side effects include issues that affect blood cell counts, liver and kidney function. Since the drugs target specific enzymes in the body, there might also be unexpected reactions related to these pathways.

Eligibility Criteria

Inclusion Criteria

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

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

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My condition is classified as high, intermediate-2, or intermediate-1 risk.

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My spleen is enlarged, extending 5 cm below my ribcage or is larger than 450 cm3 on a scan.

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I have been diagnosed with a type of myelofibrosis according to WHO criteria.

Exclusion Criteria

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

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I have never been treated with JAK inhibitors before.

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My condition worsened while I was on ruxolitinib.

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I have been treated with a BTK or BMX inhibitor before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 48 month

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~48 month

This trial's timeline: 3 weeks for screening, Varies for treatment, and 48 month for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib

Phase 2 - Spleen Volume Reduction (SVR) at Week 24

Secondary study objectives

DOR Spleen

Overall Survival

Phase 1b - Spleen Volume Reduction (SVR) at Week 24

+3 more

Trial Design

5Treatment groups

Experimental Treatment

Group I: Phase 2 - Cohort 2 suboptimal response to RuxolitinibExperimental Treatment2 Interventions

The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. The dose schedule will be the stable ruxolitinib dose schedule as the subject is currently taking prior to entry into the study.

Group II: Phase 2 - Cohort 1 JAKi treatment-naïve MFExperimental Treatment2 Interventions

The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. The dose of ruxolitinib will be based on the subject's baseline platelet count.

Group III: Phase 1b - Dose Level 3Experimental Treatment2 Interventions

450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.

Group IV: Phase 1b - Dose Level 2Experimental Treatment2 Interventions

300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.

Group V: Phase 1b - Dose Level 1Experimental Treatment2 Interventions

150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

TL-895

2020

Completed Phase 1

~10

Ruxolitinib

2018

Completed Phase 3

~1140

0 / 7Eligibility 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

Primary Myelofibrosis (PMF) treatments often involve Tyrosine Kinase Inhibitors (TKIs) such as ruxolitinib and fedratinib, which target the Janus kinase (JAK) pathway. These inhibitors block the JAK1 and JAK2 enzymes, reducing abnormal signaling that leads to excessive blood cell production and fibrosis in the bone marrow. This is crucial for PMF patients as it helps manage symptoms like splenomegaly and anemia, and can improve overall quality of life. Other treatments, such as interferon-alpha, modulate the immune system to control blood cell production, while medications like hydroxyurea reduce the number of blood cells produced. Understanding these mechanisms allows for targeted therapy, which can be more effective and have fewer side effects compared to broader treatments.