Belumosudil + Rituximab for Graft-versus-Host Disease

Overseen By Scott Solomon, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northside Hospital, Inc.

Disqualifiers: HIV, Active HBV, Active HCV, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, belumosudil (a new potential drug) and rituximab, to evaluate their effectiveness for people with chronic graft-versus-host disease (cGVHD). cGVHD can occur after a stem cell or bone marrow transplant when donor cells attack the recipient's body. The trial aims to assess the safety and effectiveness of these treatments. Suitable candidates for this trial are those experiencing their first episode of cGVHD requiring immunosuppressants and who have not yet undergone extensive treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received more than 10 days of corticosteroids or other systemic immunosuppressive agents for cGVHD before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that belumosudil is generally safe for people with chronic graft-versus-host disease (cGVHD). Earlier studies found it safe over a long period, with most people not experiencing serious side effects. The FDA has approved belumosudil for treating cGVHD that has returned or not responded to other treatments, confirming its safety record for this condition.

Rituximab has been used for many years to treat various conditions, including some autoimmune diseases and certain cancers. This extensive history provides substantial information about its safety. Most people tolerate rituximab well, although it can cause side effects in some individuals.

Together, belumosudil and rituximab have shown promising safety results in past research and approvals. While researchers continue to study the combination, these findings help reassure about their potential safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Belumosudil plus Rituximab for graft-versus-host disease because this combination offers a novel approach compared to standard treatments like corticosteroids and immunosuppressants. Belumosudil works uniquely by targeting the ROCK2 pathway, which plays a key role in immune system regulation, potentially reducing inflammation more effectively. Rituximab, known for targeting CD20 on B cells, complements this by reducing the immune response that contributes to the disease. Together, they promise a more targeted attack on the disease, which could lead to better outcomes for patients.

What evidence suggests that Belumosudil and Rituximab could be effective for graft-versus-host disease?

Research has shown that belumosudil can help treat chronic graft-versus-host disease (cGVHD). One study found that 65% of patients responded well to belumosudil, with many experiencing improvement. Patients reported a better quality of life and required fewer steroids, which are often used to manage symptoms. Belumosudil was generally well-tolerated, with benefits lasting over time. Although less direct evidence exists for using rituximab with belumosudil, rituximab targets specific immune cells and might complement belumosudil. In this trial, participants will receive a combination of these treatments, which shows promise for helping people with cGVHD. ^{1 4 6 7 8}

Who Is on the Research Team?

Scott Solomon, MD

Principal Investigator

BMTGA/Northside Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with a new diagnosis of chronic Graft-Versus-Host Disease (cGVHD) who haven't been treated yet, or have had less than 10 days of corticosteroids. Participants must be in good physical condition (KPS >/= 70%) and have adequate blood cell counts without recent transfusions. People with HIV, active hepatitis B or C, severe liver issues, poor kidney function, uncontrolled infections or heart problems cannot join.

Inclusion Criteria

My blood counts are within the required range without transfusions for a week.

I have started treatment for cGVHD less than 10 days ago.

I am mostly able to care for myself and carry out daily activities.

Exclusion Criteria

I do not have an active hepatitis B or C infection.

My kidney function is low, with a filtration rate under 30 mL/min.

I have ongoing or returning graft-versus-host disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Belumosudil and Rituximab as primary treatment for chronic graft-versus-host disease

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belumosudil
• Rituximab

Trial Overview

The study is testing the combination of two drugs—Belumosudil and Rituximab—as a primary treatment for cGVHD. It's an open-label Phase 2 trial which means everyone knows what treatment they're getting and it's fairly early in the testing process to see if it works well and is safe.

How Is the Trial Designed?

Group I: Belumosudil Plus Rituximab Experimental Treatment 2 Interventions

Belumosudil plus Rituximab

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?

Northside Hospital, Inc.

Lead Sponsor

Trials

26

Recruited

1,100+

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

Published Research Related to This Trial

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]

Rituximab, an anti-B cell therapy, shows promise in reducing the incidence and severity of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic cell transplantation, although most evidence comes from non-randomized studies using higher doses.

Rituximab is also effective in treating corticosteroid-refractory chronic GVHD, particularly for skin and mucosal symptoms, and preliminary studies suggest it may lower the rate of chronic GVHD when administered post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for prevention and treatment of graft-versus-host disease. Kharfan-Dabaja, MA., Cutler, CS.[2021]

In a retrospective analysis of 3,803 adult patients with B-cell malignancies undergoing allogeneic hematopoietic cell transplantation, the addition of rituximab to reduced intensity conditioning regimens did not significantly improve major transplant outcomes such as overall survival, disease-free survival, or non-relapse mortality.

The study found similar rates of acute graft-versus-host disease (GVHD) between patients receiving rituximab and those who did not, indicating that rituximab may not provide additional benefits in preventing GVHD in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: EBMT Registry Analyses Following Allogeneic Stem Cell Transplantation for B-Cell Malignancies. Tomaszewska, A., Jagasia, M., Beohou, E., et al.[2021]

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]

In a phase I/II trial involving 39 patients with relapsed lymphoma undergoing allogeneic stem cell transplantation, the addition of bortezomib to the rituximab plus BEAM regimen did not significantly affect the incidence of graft-versus-host disease (GVHD) or overall survival compared to a historical control group.

The study found that the maximum tolerated dose of bortezomib was 1 mg/m2, and while the R-BEAM regimen showed a survival benefit for patients aged 50 years or younger, the addition of bortezomib did not enhance this benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Transplantation after Myeloablative Rituximab/BEAM ± Bortezomib for Patients with Relapsed/Refractory Lymphoid Malignancies: 5-Year Follow-Up Results. Chamoun, K., Milton, DR., Ledesma, C., et al.[2020]

In a phase II trial involving 51 adult patients with CD20+ B cell non-Hodgkin lymphoma, a nonmyeloablative conditioning regimen with peritransplant rituximab demonstrated safety and efficacy, achieving full donor chimerism in 92% of patients after allogeneic stem cell transplant.

The 2-year overall survival rate was 78%, with significantly better event-free survival (84%) in chemosensitive patients compared to those who were chemorefractory (30%), indicating the treatment's effectiveness varies based on prior chemotherapy response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of a nonmyeloablative allogeneic stem cell transplant with peritransplant rituximab in patients with B cell lymphoid malignancies: favorably durable event-free survival in chemosensitive patients. Sauter, CS., Barker, JN., Lechner, L., et al.[2021]

In a study of 435 B-cell lymphoma patients undergoing allogeneic transplantation, those who received rituximab within 6 months prior to the procedure had significantly lower rates of treatment-related mortality and acute graft-versus-host disease (GVHD).

Patients in the rituximab cohort also experienced better progression-free survival and overall survival compared to those who did not receive rituximab, indicating that prior rituximab therapy may enhance transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prior rituximab correlates with less acute graft-versus-host disease and better survival in B-cell lymphoma patients who received allogeneic peripheral blood stem cell transplantation. Ratanatharathorn, V., Logan, B., Wang, D., et al.[2021]

Rituximab, a monoclonal antibody primarily used for CD20-positive B-cell malignancies and rheumatoid arthritis, is being explored for its effectiveness in treating acute graft-versus-host disease (aGVHD) in critically ill patients.

The study aims to evaluate the safety of rituximab in this context, particularly focusing on its potential links to infectious complications in transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in critically ill patients. Dimopoulos, G., Armaganidis, A., Poulakou, G., et al.[2019]

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]

In a study of 102 Chinese patients who underwent allogeneic hematopoietic stem cell transplantation, Rituximab was found to significantly reduce the incidence of chronic graft-versus-host disease (cGVHD) compared to those who did not receive the treatment.

Importantly, the use of Rituximab did not increase the risk of relapse or transplantation-related mortality, suggesting it is a safe option for preventing cGVHD in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective Effect of Rituximab in Chronic Graft-Versus-Host Disease Occurrence in Allogeneic Transplant patients with Epstein Barr Virus Viremia. Ji, SM., Bao, XB., Lu, J., et al.[2020]

Rituximab, an anti-CD20 monoclonal antibody, was found to be well tolerated in a small group of 7 patients with corticosteroid-refractory chronic graft-versus-host disease (GVHD), with no severe toxicity reported during the treatment.

Out of the 7 patients treated, 3 showed a partial response and 4 were able to reduce their steroid dosage, indicating that rituximab may be effective for certain patients with less severe manifestations of chronic GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease. Teshima, T., Nagafuji, K., Henzan, H., et al.[2021]

In a study of 159 allogeneic hematopoietic stem cell transplant patients, rituximab-containing conditioning regimens did not significantly reduce the incidence of grade II-IV acute graft-versus-host disease compared to those without rituximab (37% vs. 26%).

Interestingly, among patients receiving peripheral blood stem cell transplants, those treated with rituximab had a higher incidence of acute graft-versus-host disease, relapse, or death prior to day 100 (55% vs. 36%), suggesting that rituximab may not be beneficial and could potentially worsen outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of graft-versus-host disease with rituximab-containing conditioning regimens in allogeneic hematopoietic stem cell transplant. Marini, BL., Markstrom, D., Frame, D.[2018]

Citations

1.

trial.medpath.com

trial.medpath.com/clinical-trial/64c4ee3003785660/nct06046248-belumosudil-rituximab-chronic-graft-versus-host-disease

Belumosudil and Rituximab for Primary Treatment of Chronic ...

This is an open-label, Phase 2 study designed to evaluate the safety and efficacy of belumosudil and rituximab as primary treatment of cGVHD.

2.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK613418/

Belumosudil for treating chronic graft-versus-host disease ...

Clinical trial evidence suggests that taking belumosudil improves people's symptoms, but it was not compared directly with best available ...

3.

ashpublications.org

ashpublications.org/blood/article/138/22/2278/476399/Belumosudil-for-chronic-graft-versus-host-disease

Belumosudil for chronic graft-versus-host disease after 2 or ...

In that study, belumosudil demonstrated a pooled ORR of 65%, improvements in QOL (as measured by the LSS) and reductions in CS use in subjects ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03640481

NCT03640481 | Efficacy and Safety of KD025 in Subjects ...

This is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with Chronic Graft Versus Host Disease (cGVHD)

5.

astctjournal.org

astctjournal.org/article/S2666-6367(25)01159-5/fulltext

Analysis of Long-Term Results from the KD025-208 and ...

Durability of response was shown through an increase in DOR, FFS, and TTNT. •. Belumosudil was well tolerated in patients with cGVHD after long-term follow-up.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11971036/

Safety and efficacy of the ROCK-2-inhibitor Belumosudil in ...

In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03640481

NCT03640481 | Efficacy and Safety of KD025 in Subjects ...

Correlation of Patient-Reported Outcomes with Clinical Organ Responses: Data from the Belumosudil Chronic Graft-versus-Host Disease Studies. Transplant Cell ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2473952925005373/pdf?md5=04b0d5b9ea9b9f87fe084bb751fb7901&pid=1-s2.0-S2473952925005373-main.pdf

Efficacy and Safety of Belumosudil as Compared with Best ...

Belumosudil was FDA-approved in the United States (US) for the treatment of relapsed/refractory chronic graft-versus-host disease (cGVHD) based ...