Belumosudil for Multiple Myeloma

Overseen By Robert Orlowski, M D

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiretrovirals

Disqualifiers: Active hepatitis, Active CNS involvement, others

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

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: Unknown

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1 is to find the recommended dose of belumosudil mesylate that can be given to patients with relapsed/refractory MM. Phase 2 is to learn if the dose of belumosudil mesylate found in Phase 1 can help to control the disease.

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 must have completed any radiation therapy or corticosteroids for myeloma at least 2 weeks before starting the trial. You can continue using corticosteroids for other conditions if the dose is low.

Is Belumosudil safe for humans?

Belumosudil has been studied in humans for conditions like chronic graft-versus-host disease, and it was generally well tolerated with no notable adverse events reported in trials. Some participants discontinued due to possible drug-related side effects, but overall, it was considered safe in the studies conducted. ^{1 2 3 4 5}

What makes the drug Belumosudil unique for treating multiple myeloma?

Belumosudil is unique because it targets a specific pathway involved in immune system regulation, which may offer a novel approach compared to traditional treatments that focus on directly attacking cancer cells. This mechanism could provide an alternative for patients who have not responded well to existing therapies. ^{6 7 8 9 10}

Research Team

Robert Z. Orlowski, M.D., Ph.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with relapsed/refractory multiple myeloma who've tried at least three treatments and still have measurable disease. They must be in fair to good health (ECOG PS of 0-3 if due to the disease), agree to use contraception, and not be on certain anti-HIV drugs or have other serious illnesses or second cancers.

Inclusion Criteria

I was diagnosed with multiple myeloma based on a tissue or cell test.

I have multiple myeloma that didn't respond to 3+ treatments, including 3 types of drugs.

My blood, liver, heart, and kidney functions are all good, and if I have HIV, my CD4+ count is over 1,000 without anti-retroviral therapy.

Exclusion Criteria

I do not have severe health issues or other cancers, and I am not HIV positive on antiretroviral therapy.

I am not on any experimental treatments for myeloma and my side effects from previous treatments have mostly gone away.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Define the toxicities and recommended Phase II dose (RP2D) of belumosudil mesylate in patients with relapsed/refractory multiple myeloma.

8-12 weeks

Phase 2: Dose Expansion

Obtain preliminary evidence of efficacy of belumosudil mesylate and further expand the safety experience in this patient population.

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Belumosudil Mesylate

Trial Overview The study is testing Belumosudil mesylate's effectiveness alone and combined with Dexamethasone in two phases. Phase I determines the safest dose, while Phase II checks if that dose can control multiple myeloma symptoms.

Participant Groups

Group I: Phase 2 (dose expansion) Experimental Treatment 1 Intervention

Phase 2, participants will receive belumosudil mesylate at the recommended dose that was found in Phase 1.

Group II: Phase 1 (dose escalation) Experimental Treatment 1 Intervention

Phase 1, the dose of belumosudil mesylate participants receive will depend on when participants join this study. The first group of participants will receive the lowest dose level of belumosudil mesylate.

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

Approved in United States as Rezurock for:

• Chronic graft-versus-host disease (cGvHD)

Approved in Canada as Rholistiq for:

• Chronic graft-versus-host disease (cGvHD)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Sanofi US Services, Inc

Collaborator

Trials

1

Recruited

40+

Findings from Research

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]

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 (BLM) is a ROCK inhibitor approved by the FDA for treating chronic graft-versus-host disease (cGVHD) in patients aged 12 and older who have not responded to at least two prior therapies, highlighting its efficacy in a challenging patient population.

BLM received breakthrough therapy designation and orphan drug status, indicating its potential significance in treating rare diseases like cGVHD and systemic sclerosis, and it is currently undergoing further regulatory assessments and clinical trials for additional indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil with ROCK-2 inhibition: chemical and therapeutic development to FDA approval for the treatment of chronic graft-versus-host disease. Ali, F., Ilyas, A.[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]

Patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with either ravulizumab or eculizumab for 26 weeks reported better quality of life and functioning compared to the general population, indicating the efficacy of these treatments.

Ravulizumab showed larger effect sizes than eculizumab, and both treatments facilitated adaptive changes in patients' responses over time, suggesting they not only manage symptoms but also improve overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Schwartz, CE., Stark, RB., Borowiec, K., et al.[2021]

In a phase I trial involving 28 patients with relapsed/refractory multiple myeloma, ruxolitinib combined with lenalidomide and methylprednisolone showed a clinical benefit rate of 46% and an overall response rate of 38%, indicating its potential effectiveness in overcoming resistance to lenalidomide.

The trial reported no dose-limiting toxicities, suggesting that ruxolitinib is safe to use in this combination therapy, although some patients experienced grade 3 or 4 adverse events like anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple Myeloma. Berenson, JR., To, J., Spektor, TM., et al.[2021]

Idecabtagene vicleucel (ide-cel) significantly improves progression-free survival (PFS) and overall survival (OS) in patients with relapsed and refractory multiple myeloma compared to the approved therapies selinexor plus dexamethasone and belantamab mafodotin, based on data from the phase 2 KarMMa trial.

The hazard ratios indicate that ide-cel offers substantial clinical benefits, with a PFS hazard ratio of 0.46 versus selinexor and 0.45 versus belantamab, and an OS hazard ratio of 0.23 versus selinexor and 0.35 versus belantamab, suggesting it is a promising treatment option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching adjusted indirect comparisons of efficacy outcomes for idecabtagene vicleucel (ide-cel, bb2121) versus selinexor + dexamethasone and belantamab mafodotin in relapsed and refractory multiple myeloma. Rodriguez-Otero, P., Ayers, D., Cope, S., et al.[2021]

In a subgroup analysis of the phase 3 CANDOR study involving 66 Asian patients with relapsed/refractory multiple myeloma, the KdD treatment reduced the risk of disease progression or death by 25% compared to Kd, indicating improved efficacy.

While KdD showed a trend towards better efficacy, it also had a higher incidence of serious adverse events (58.7% vs. 40.0% in Kd), highlighting the need for careful consideration of the benefit-risk profile in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab in Asian patients with relapsed or refractory multiple myeloma: post hoc subgroup analysis of the phase 3 CANDOR trial. Suzuki, K., Min, CK., Kim, K., et al.[2022]

The introduction of novel agents for treating relapsed and/or refractory multiple myeloma (RRMM) has significantly improved response rates, rising from about 30% with single agents to up to 90% with combination therapies.

Newer treatments, including pomalidomide, panobinostat, carfilzomib, ixazomib, and monoclonal antibodies like daratumumab and elotuzumab, have enhanced overall response rates, even in heavily pretreated patients, while also improving the tolerability of treatment regimens and health-related quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients? Sonneveld, P., De Wit, E., Moreau, P.[2022]

In a phase 2 study of 38 patients with relapsed/refractory multiple myeloma and varying degrees of renal impairment, the recommended dose adjustments for lenalidomide resulted in appropriate plasma exposure and a high overall response rate of 76%.

The safety profiles were consistent across different levels of renal function, indicating that the dosing adjustments based on creatinine clearance were effective and did not lead to increased toxicity or reduced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, safety, and efficacy of lenalidomide plus dexamethasone in patients with multiple myeloma and renal impairment. Bridoux, F., Chen, N., Moreau, S., et al.[2018]

References

1. 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]

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

Belumosudil: First Approval. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Belumosudil with ROCK-2 inhibition: chemical and therapeutic development to FDA approval for the treatment of chronic graft-versus-host disease. [2022]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. [2021]

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

A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple Myeloma. [2021]

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

Matching adjusted indirect comparisons of efficacy outcomes for idecabtagene vicleucel (ide-cel, bb2121) versus selinexor + dexamethasone and belantamab mafodotin in relapsed and refractory multiple myeloma. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab in Asian patients with relapsed or refractory multiple myeloma: post hoc subgroup analysis of the phase 3 CANDOR trial. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients? [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, safety, and efficacy of lenalidomide plus dexamethasone in patients with multiple myeloma and renal impairment. [2018]