Vimseltinib for Chronic Graft-Versus-Host Disease

Recruiting at 5 trial locations

Overseen By Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Deciphera Pharmaceuticals, LLC

Must not be taking: CSF1R inhibitors

Disqualifiers: Severe illness, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

36 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if vimseltinib is safe, tolerable and works effectively to treat adults with active moderate to severe cGVHD. Participants will be treated with vimseltinib in 28-day treatment cycles for approximately 2 years.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you can stay on a stable dose of corticosteroids if needed. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Vimseltinib for chronic graft-versus-host disease?

While there is no direct data on Vimseltinib for chronic graft-versus-host disease, similar drugs like imatinib and ruxolitinib, which are also tyrosine kinase inhibitors, have shown promising results in treating this condition. For example, imatinib has been effective in patients with fibrotic chronic graft-versus-host disease, achieving a 79% overall response rate in a study. ^{1 2 3 4 5}

How is the drug Vimseltinib different from other drugs for chronic graft-versus-host disease?

Vimseltinib is unique because it targets specific pathways involved in chronic graft-versus-host disease, potentially offering a new approach compared to existing treatments like steroids and tyrosine kinase inhibitors, which have varying effectiveness and side effects. This drug may provide an alternative for patients who do not respond well to current therapies. ^{1 3 5 6 7}

Research Team

Clinical Team

Principal Investigator

Deciphera Pharmaceuticals, LLC

Eligibility Criteria

This trial is for adults with active moderate to severe chronic Graft-Versus-Host Disease (cGVHD) after stem cell transplant. They must have tried at least two other treatments without success, be able to do most activities (KPS ≥60), and may still have some acute GVHD symptoms. Stable use of steroids is okay, and they need good organ/bone marrow function.

Inclusion Criteria

I received a stem cell transplant and need treatment for a severe reaction.

I may have ongoing symptoms of both acute and chronic graft-versus-host disease.

I have chronic GVHD and two treatments haven't worked for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of vimseltinib in 28-day cycles for approximately 2 years

24 months

Monthly visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vimseltinib

Trial Overview The study tests Vimseltinib's safety and effectiveness in treating cGVHD over approximately 2 years. Participants will undergo treatment cycles lasting 28 days each with the goal of reducing the severity of their condition.

Participant Groups

Group I: Vimseltinib Experimental Treatment 1 Intervention

Escalating doses of vimseltinib in 28 day cycles.

Who Is Running the Clinical Trial?

Deciphera Pharmaceuticals, LLC

Lead Sponsor

Trials

19

Recruited

2,100+

Findings from Research

In a study of 8 patients with severe sclerotic chronic graft-vs-host disease (scGVHD), dasatinib showed a higher response rate of 60% compared to 25% for imatinib, indicating it may be a more effective treatment option.

Dasatinib was better tolerated and had a lower incidence of serious side effects, making it a safer and steroid-sparing alternative for patients who are refractory to imatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib and dasatinib as salvage therapy for sclerotic chronic graft-vs-host disease. Sánchez-Ortega, I., Parody, R., Servitje, O., et al.[2019]

Ruxolitinib (Jakafi) has received approval for the treatment of chronic graft-vs-host disease, indicating its efficacy in managing this condition.

The approval of ruxolitinib highlights its role as a kinase inhibitor, which works by targeting specific pathways involved in the immune response, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indication for Ruxolitinib. Aschenbrenner, DS.[2023]

The study by Flynn et al. supports the potential of spleen tyrosine kinase (Syk) inhibition as a promising treatment strategy for chronic graft-versus-host disease (cGVHD).

These findings provide a strong rationale for advancing clinical trials to evaluate the efficacy and safety of Syk inhibitors in cGVHD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Syk and tired of current chronic GVHD therapies. Fowler, DH., Pavletic, SZ.[2021]

In a study of 43 patients with chronic graft-versus-host disease (cGVHD) treated with tyrosine kinase inhibitors (TKIs), overall response rates improved over time, with 58.6% responding by 12 months, and 80% of patients experienced clinical benefits allowing for corticosteroid dose reductions.

Ruxolitinib was found to be as effective as imatinib in treating sclerotic GVHD, with similar overall survival rates of 96%-100% across all TKI treatments, indicating that these drugs are both effective and feasible options for managing cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-center, Real-world Experience of Chronic GVHD Treatment Using Ibrutinib, Imatinib, and Ruxolitinib and its Treatment Outcomes. Linn, SM., Novitzky-Basso, I., Abduljalil, O., et al.[2023]

In a pilot study of 19 patients with refractory chronic graft-versus-host disease (cGVHD), imatinib showed a high overall response rate of 79% at 6 months, with 7 complete remissions and 8 partial remissions, indicating its efficacy as a treatment option.

Despite some patients experiencing significant side effects leading to discontinuation of the drug, the 18-month overall survival probability was 84%, suggesting that imatinib can be a promising therapy for patients with difficult-to-treat fibrotic cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib for refractory chronic graft-versus-host disease with fibrotic features. Olivieri, A., Locatelli, F., Zecca, M., et al.[2021]

Steroid refractory chronic graft-versus-host disease (cGVHD) has limited treatment options, primarily based on phase II trials and retrospective analyses, highlighting the need for more systematic evaluations of second-line therapies.

Current treatment modalities include a variety of agents such as steroids, calcineurin inhibitors, and newer options like tyrosine kinase inhibitors, but the effectiveness of these treatments often relies on a trial-and-error approach, emphasizing the need for valid biomarkers to predict patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease. Wolff, D., Schleuning, M., von Harsdorf, S., et al.[2015]

Imatinib, a tyrosine kinase inhibitor, was used to treat a patient with cutaneous graft versus host disease (GvHD) resistant to steroids, but it led to complications including multiorgan failure due to low cardiac output.

The study highlights the diagnostic challenge of pericardial effusion and suggests that monitoring lactate levels, central venous pressure, venous saturation, and brain natriuretic peptide can aid in early detection of cardiac issues in such patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac tamponade and graft versus host disease: one more reason to remember. Vetrugno, L., Tomasino, S., Battezzi, A., et al.[2022]

References

1. Croatia pubmed.ncbi.nlm.nih.gov

Imatinib and dasatinib as salvage therapy for sclerotic chronic graft-vs-host disease. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

New Indication for Ruxolitinib. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Syk and tired of current chronic GVHD therapies. [2021]

4. Saudi Arabia pubmed.ncbi.nlm.nih.gov

A Single-center, Real-world Experience of Chronic GVHD Treatment Using Ibrutinib, Imatinib, and Ruxolitinib and its Treatment Outcomes. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Imatinib for refractory chronic graft-versus-host disease with fibrotic features. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Cardiac tamponade and graft versus host disease: one more reason to remember. [2022]