Belumosudil for Graft-versus-Host Disease

Recruiting at 5 trial locations

Overseen By Gaby Desatnik

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Systemic immunosuppressants, Investigational agents

Disqualifiers: Uncontrolled psychiatric illness, Pregnancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 months

82 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial compares the effect of belumosudil to a placebo in treating patients with chronic graft versus host disease. Chronic graft versus host disease remains a major complication of stem cell transplantation and can involve multiple organ systems. Belumosudil is a ROCK2 selective inhibitor that works to reduce the immune system response causing the chronic graft versus host disease. Giving belumosudil may better treat patients with chronic graft versus host disease and prevent the need for starting additional immune suppressive medications.

Will I have to stop taking my current medications?

The trial allows you to continue medications you were already taking for graft-versus-host disease, but you cannot start new immune suppressive treatments or increase your steroid dose within 14 days before starting the study medication.

What data supports the effectiveness of the drug Belumosudil for treating graft-versus-host disease?

Belumosudil has shown promising results in treating chronic graft-versus-host disease (cGVHD), with a high overall response rate of 74-77% in patients who had tried at least two other treatments. It was well tolerated and led to symptom reduction in over half of the patients, making it a promising option for those with cGVHD. ^{1 2 3 4 5}

Is Belumosudil safe for humans?

Belumosudil has been studied for safety in patients with chronic graft-versus-host disease (cGVHD). Common side effects include infections, weakness, nausea, diarrhea, and high blood pressure. Some patients stopped using it due to possible drug-related side effects, but overall, it was generally well tolerated. ^{2 3 4 5 6}

What makes the drug Belumosudil unique for treating graft-versus-host disease?

Belumosudil is unique because it is the first and only approved drug that specifically targets ROCK2, a protein involved in inflammation and fibrosis, making it effective for patients with chronic graft-versus-host disease who have not responded to at least two other treatments. It is taken orally and has shown high response rates and symptom reduction in clinical trials. ^{1 3 4 7 8}

Research Team

Stephanie Lee, MD, MPH

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with chronic graft versus host disease who can take oral meds, have a good performance status (Karnofsky score >= 70), and normal organ function. Women of childbearing potential must use two forms of contraception and not be pregnant or breastfeeding. Participants cannot have used belumosudil before, be on high-dose steroids, or plan to start new immune suppressive treatments.

Inclusion Criteria

Your kidneys are working well, with a filtration rate of at least 30 milliliters per minute per 1.73 square meters of body surface area.

I do not have any signs of active cancer.

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

Treatment with another investigational agent within 28 days (or 5 half-lives, whichever is greater) of enrollment

I have been treated with belumosudil before.

I am currently pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belumosudil or placebo orally daily or twice daily for 28-day cycles, repeated for a total of 11 cycles, followed by one cycle of tapering

12 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 months

2 visits (in-person) at 30 and 60 days post-treatment

Treatment Details

Interventions

• Belumosudil

Trial Overview The study compares the effects of Belumosudil, a drug that may reduce immune response in chronic graft versus host disease, against a placebo. It aims to see if Belumosudil can better treat patients without needing additional immune suppressants.

Participant Groups

Group I: Arm I (Belumosudil) Experimental Treatment 3 Interventions

Patients receive belumosudil PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.

Group II: Arm II (Placebo) Placebo Group 3 Interventions

Patients receive a placebo PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.

Belumosudil is already approved in United States, Canada for the following indications:

Approved in United States as Rezurock for:

• Chronic graft-versus-host disease (cGVHD) in patients aged 12 years and older after failure of at least two prior lines of systemic therapy

Approved in Canada as Rholistiq for:

• Chronic graft-versus-host disease (cGVHD) in adult and pediatric patients 12 years or older

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

Belumosudil mesylate is the first and only FDA-approved selective ROCK2 inhibitor for treating chronic graft-versus-host disease (cGvHD) in patients aged 12 and older who have not responded to at least two prior treatments.

The drug has shown both safety and efficacy in clinical studies, targeting the dysregulated ROCK pathway that contributes to inflammation and fibrosis in cGvHD, a condition affecting up to 70% of patients after allogeneic hematopoietic cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil for chronic graft-versus-host disease. Taylor, B., Cohen, J., Tejeda, J., et al.[2022]

Belumosudil, a kinase inhibitor, was approved by the FDA for treating chronic GvHD in patients aged 12 and older after failing at least two prior therapies, showing a 75% overall response rate in a study of 65 patients.

While 69% of patients achieved a partial response, the treatment was associated with common side effects such as infections and nausea, indicating the need for further studies to assess long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy. Przepiorka, D., Le, RQ., Ionan, A., et al.[2022]

Belumosudil, an oral medication targeting ROCK2, showed a high overall response rate of 74% for the 200 mg daily dose and 77% for the 200 mg twice daily dose in patients with chronic graft-versus-host disease (cGVHD) after multiple prior treatments, indicating its efficacy in this challenging condition.

The treatment was well tolerated, with a median duration of response of 54 weeks and significant symptom reduction in 59% to 62% of subjects, while adverse events were consistent with those expected in cGVHD patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Cutler, C., Lee, SJ., Arai, S., et al.[2022]

Belumosudil (REZUROCK™) is a newly approved ROCK inhibitor specifically designed for treating chronic graft-versus-host disease (cGVHD) in patients aged 12 and older who have not responded to at least two prior treatments.

The drug has received regulatory approval in the USA and is currently under review in several other countries, with ongoing clinical development for systemic sclerosis, highlighting its potential as a significant therapeutic option for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil: First Approval. Blair, HA.[2022]

Belumosudil, a new oral medication, showed a 32% overall response rate in treating lung cGVHD (bronchiolitis obliterans syndrome) in 59 patients, with better outcomes in those with less severe disease.

Response rates were significantly higher in patients with lower NIH lung scores at enrollment, indicating that earlier intervention may lead to better treatment results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials. DeFilipp, Z., Kim, HT., Yang, Z., et al.[2023]

Sirolimus (SRL) significantly reduces the incidence of grade II-IV acute graft-versus-host disease (GVHD) in patients following allogeneic hematopoietic stem cell transplantation, based on a meta-analysis of 1,673 cases from seven studies.

While SRL-based regimens do not increase the risk of common infections, they are associated with a higher incidence of thrombotic microangiopathy (TMA) and veno-occlusive disease (VOD), indicating potential safety concerns despite their efficacy in preventing GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Addition of Sirolimus to GVHD Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Efficacy and Safety. Chen, X., Sun, H., Cassady, K., et al.[2022]

Belumosudil, a selective Rho-associated protein kinase 2 inhibitor, shows promise in treating chronic graft-versus-host disease by restoring immune balance and reducing fibrosis, with no significant adverse events reported during the study.

The pharmacokinetics of belumosudil are significantly affected by other medications, such as itraconazole and rifampicin, indicating that dosage adjustments may be necessary when coadministered with proton pump inhibitors like rabeprazole and omeprazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors. Schueller, O., Willson, A., Singh, N., et al.[2022]

In a study of 37 patients with chronic graft-versus-host disease, the addition of the ROCK2 inhibitor Belumosudil (BEL) significantly increased the concentration-dose (C/D) ratios of sirolimus by 160% and tacrolimus by 113%, indicating that dosage adjustments for these immunosuppressive drugs are necessary when starting BEL.

A notable percentage of patients experienced supratherapeutic levels of sirolimus (57%) and tacrolimus (19%) after initiating BEL, highlighting the potential risk for toxicity and the need for close monitoring and possible dose reductions of 25% for tacrolimus and 25% to 50% for sirolimus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil Impacts Immunosuppression Pharmacokinetics in Patients with Chronic Graft-versus-Host Disease. Gonzalez, R., Gaskill, E., Padilla, M., et al.[2023]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Belumosudil for chronic graft-versus-host disease. [2022]

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

FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy. [2022]

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

Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Belumosudil: First Approval. [2022]

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

Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Addition of Sirolimus to GVHD Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Efficacy and Safety. [2022]

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

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors. [2022]

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

Belumosudil Impacts Immunosuppression Pharmacokinetics in Patients with Chronic Graft-versus-Host Disease. [2023]