Belumosudil for the Pre-emptive Treatment of Patients With Chronic Graft Versus Host Disease

NCT05996627 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1123523NCI-2023-0529320163
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Chronic Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• Time to start of subsequent systemic immune suppressive treatment for chronic graft versus host disease (cGVHD)

  Systemic therapies include any systemic agent given for a cGVHD indication, including extracorporeal photopheresis. Will use Gray's test. Point estimates of new systemic immunosuppressive use will be obtained using cumulative incidence estimates.

  From first dose of study medication to starting a new systemic immunosuppressive agent for cGVHD therapy, up to 12 months

Secondary Outcomes (3)

• Event-free survival

  From randomization to death, malignancy relapse or addition of a new systemic immune suppressive therapy, up to 12 months or end of study

• Overall survival

  Up to 12 months or end of study

• Rate of relapse

  Up to 12 months or end of study

Study Arms (2)

Arm I (Belumosudil)

EXPERIMENTAL

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.

Drug: Belumosudil; Procedure: Biospecimen Collection; Other: Electronic Health Record Review

Arm II (Placebo)

PLACEBO COMPARATOR

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.

Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Drug: Placebo Administration

Interventions

Placebo Administration DRUG

Given PO

Arm II (Placebo)

Belumosudil DRUG

Given PO

Also known as: KD 025, KD-025, KD025, Rho-associated Coiled-coil Kinase 2 Inhibitor KD025, ROCK-II Inhibitor KD025, ROCK2 Inhibitor KD025, SLx 2119, SLx-2119, SLx2119

Arm I (Belumosudil)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (Belumosudil); Arm II (Placebo)

Electronic Health Record Review OTHER

Ancillary studies

Arm I (Belumosudil); Arm II (Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least one diagnostic or distinctive cGVHD manifestation(s), with a clinical diagnosis of cGVHD,but patients do not need to meet National Institute of Health (NIH) criteria for cGVHD
• If eye involvement only, cGVHD must be confirmed on exam by an ophthalmologist or optometrist
• No new immune suppressive therapy added within preceding 2 weeks prior to study enrollment for any indication
• Continuation of agents previously given as either GVHD prophylaxis or acute/late acute GVHD therapy are permitted. Modification of dose of these agents for targeting of therapeutic drug levels is permitted, as are decreases in existing prednisone or prednisone equivalent dose based on routine clinical tapering practices. Increases in prednisone or prednisone equivalents are not allowed in the 2 weeks prior to enrollment
• Age 18 and older
• Karnofsky performance score \>= 70
• Able to take oral medications
• Signed informed consent
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN)
• Total bilirubin =\< 1.5 x ULN, unless due to Gilbert's disease
• Glomerular filtration rate (estimated glomerular filtration rate \[eGFR\]) \>= 30 mL/min/1.73 m\^2
• Female subjects of childbearing potential have a negative serum or urine pregnancy test at screening. Females of childbearing potential are defined as sexually mature females without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, females who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression
• Sexually active females of childbearing potential enrolled in the study must agree to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes:
• Intrauterine device (IUD) plus one barrier method
• Stable doses of hormonal contraception for at least 3 months (eg, oral, injectable, implant, transdermal) plus one barrier method

You may not qualify if:

• Any systemic immune suppressive treatment for cGVHD (topical or local therapies are allowed)
• Plan to start systemic immune suppressive therapy for cGVHD or increase steroid dose within 14 days after planned start of study medication
• mg/kg/day or higher prednisone or prednisone equivalent dose at time of screening
• History of non-compliance that in the investigator's opinion would interfere with study participation
• Uncontrolled psychiatric illness
• Female subject who is pregnant or breast feeding
• Previous therapy with belumosudil
• Known allergy/sensitivity to belumosudil or any other ROCK2 inhibitor
• Treatment with another investigational agent within 28 days (or 5 half-lives, whichever is greater) of enrollment

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Sanofi: collaborator

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

belumosudil; KD025; Specimen Handling

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Stephanie Lee, MD, MPH

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gaby Desatnik

CONTACT

206-667-1356; gdesatni@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The study will be conducted in a double-blinded fashion
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2023
• First Posted: August 18, 2023
• Study Start: December 6, 2023
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)