Belumosudil Versus Ruxolitinib for Steroid-Refractory or Breakthrough Hepatic cGVHD

August 28, 2026 updated by: Yanmin Zhao, First Affiliated Hospital of Zhejiang University

Belumosudil Versus Ruxolitinib for Steroid-Refractory or Breakthrough Hepatic cGVHD: A Prospective, Multicenter Study With Randomization in Treatment-Naïve Patients and Switch in Pretreated Patients

This prospective, randomized, open-label, multicenter trial aims to compare second-line treatment strategies for hepatic cGVHD after allo-HSCT. Ruxolitinib and belumosudil are both effective for cGVHD, but no head-to-head comparison specifically in hepatic cGVHD has been reported. Two cohorts are enrolled: Cohort 1 comprises patients with steroid-refractory hepatic cGVHD without prior ruxolitinib or belumosudil exposure, randomized to receive either agent. Cohort 2 includes patients who develop new-onset hepatic cGVHD after ≥4 weeks of therapy with ruxolitinib or belumosudil for other-organ cGVHD (stable for ≥2 weeks), or patients with non-response/progression on either agent for hepatic cGVHD; these patients will be switched to the opposite drug. Key questions include: • In steroid-refractory hepatic cGVHD, does 24-week hepatic overall response rate differ between belumosudil and ruxolitinib? • What is the hepatic response rate after drug switching in Cohort 2? • How do the two agents compare in safety and tolerability for hepatic cGVHD? • What are their impacts on corticosteroid tapering, failure-free survival, and long-term outcomes? Participants will: • Receive assigned treatment per cohort and randomization • Undergo regular efficacy/safety monitoring, including hepatic cGVHD scoring, liver function tests, and adverse event recording • Provide peripheral blood samples at baseline and multiple on-treatment time points for exploratory biomarker analysis • Complete 24-week primary efficacy assessment with follow-up until progression or discontinuation Primary endpoint is 24-week hepatic overall response rate (CR+PR, per 2014 NIH cGVHD criteria). Secondary endpoints include duration of response, failure-free survival, corticosteroid tapering rate, safety (AE/SAE incidence), liver function improvement, and patient-reported outcomes. This head-to-head comparison will provide high-level evidence for selecting second-line and beyond therapies for hepatic cGVHD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

170

Phase

Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Fei Gao
Phone Number: +86 19857035073
Email: gf0906@zju.edu.cn

Study Locations

China
- Zhejiang
  - Hangzhou, Zhejiang, China, 310006
    - Recruiting
    - The First Affiliated Hospital of Zhejiang University school of medicine
    - Contact:
      
      Yanmin Zhao, MD
      
      Phone Number: 057187236706
      
      Email: yanminzhao@zju.edu.cn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult
Older Adult

Accepts Healthy Volunteers

Description

Inclusion Criteria:

Age ≥ 12 years at time of signing informed consent.
Received allogeneic hematopoietic stem cell transplantation.
Meets 2014 NIH consensus criteria for hepatic cGVHD (≥1 of: total bilirubin > 2×ULN, ALP > 2×ULN, ALT > 2×ULN, or liver biopsy-proven cGVHD-related injury), after excluding other causes.
ECOG performance status ≤ 2.
Able to take oral medication.
Life expectancy ≥ 6 months.
Adequate organ function: ANC ≥ 1.0×10⁹/L, platelets ≥ 50×10⁹/L, creatinine clearance ≥ 30 mL/min.
Female patients of childbearing potential have negative pregnancy test and agree to effective contraception during study and for 6 months after last dose; male patients agree to same.
Willing and able to provide written informed consent and comply with study requirements.
Cohort 1 (Steroid-refractory): Progressive disease on stable steroids (1 mg/kg/day) within 1-2 weeks prior to screening, or persistent cGVHD without improvement after ≥4 weeks of prednisone (or equivalent) > 0.5 mg/kg/day. (Prior aGVHD JAK inhibitor use allowed if stopped ≥8 weeks.).
Cohort 2 (Breakthrough hepatic cGVHD): Patients on stable (≥2 weeks) ruxolitinib or belumosudil monotherapy for non-hepatic cGVHD for ≥4 weeks, who develop new-onset hepatic cGVHD or experience no response or progression on current therapy for hepatic cGVHD, not attributable to other etiologies (e.g., viral hepatitis, drug-induced liver injury, biliary obstruction, iron overload, alcoholic liver disease), with no prior exposure to the alternative study agent.

Exclusion Criteria:

Receiving newly initiated systemic cGVHD therapy other than corticosteroids and calcineurin inhibitors (CNIs); corticosteroids and CNIs must be on a stable regimen for ≥2 weeks prior to screening.
Uncontrolled active acute GVHD (≥ grade 2).
Active viral hepatitis or HIV infection.
Liver function abnormalities due to other causes, including but not limited to drug-induced liver injury, autoimmune hepatitis, alcoholic liver disease, biliary obstruction, VOD/SOS, iron overload, Gilbert's syndrome, or hemolysis.
Severe cardiovascular or cerebrovascular disease, including but not limited to: NYHA class ≥3, uncontrolled hypertension, severe arrhythmia, or myocardial infarction/stroke within 6 months.
Respiratory failure requiring mechanical ventilation, resting pulse oxygen saturation <90%, or severe/uncontrolled pulmonary cGVHD or other respiratory disease that may significantly affect patient safety or study assessment, per investigator judgment.
Inability to take oral medication, severe gastrointestinal dysfunction (NCI CTCAE v5.0 ≥ grade 3), severe GI cGVHD requiring parenteral nutrition, daily diarrhea >1 L, or any other condition significantly affecting GI absorption.
Significant neurological or psychiatric history (including epilepsy or dementia) that makes the subject unsuitable for participation.
Relapsed primary malignancy or PTLD.
History of other malignancies, except cured and fully resected basal or squamous cell skin carcinoma, surgically cured cervical carcinoma in situ, resected ductal carcinoma in situ of the breast, prostate cancer (Gleason <6 with stable PSA >12 months), or other malignancies with no evidence of recurrence after curative treatment.
ECG abnormality: QTcF >450 ms (male) or >470 ms (female) at screening.
Known alcohol or drug dependence.
Pregnant or breastfeeding women.
Allergy to study drug or its excipients.
Any other condition that may affect patient safety or compliance, per investigator judgment.
Cohort 1: Prior cGVHD treatment with JAK inhibitors (e.g., ruxolitinib) or ROCK2 inhibitors (e.g., belumosudil); receipt of other investigational therapy within 30 days prior to randomization, or <5 half-lives since last investigational product.
Cohort 2: Patients with prior exposure to both ruxolitinib and belumosudil.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ruxolitinib Group Participants assigned to this arm will receive ruxolitinib administered orally at the standard approved dose and schedule for the treatment of steroid-refractory hepatic chronic graft-versus-host disease (cGVHD).	Drug: Ruxolitinib treatment Ruxolitinib treatment
Experimental: Belumosudil Group Participants assigned to this arm will receive belumosudil administered orally at the standard approved dose and schedule for the treatment of steroid-refractory hepatic chronic graft-versus-host disease (cGVHD).	Drug: Belumosudil treatment Belumosudil treatment
Other: Belumosudil Switch to Ruxolitinib Group Participants with breakthrough hepatic cGVHD on stable belumosudil therapy for non-hepatic cGVHD who develop new-onset hepatic cGVHD or have no response/progression on belumosudil, not attributable to other etiologies, and with no prior ruxolitinib exposure, will discontinue belumosudil and cross over to ruxolitinib.	Drug: Belumosudil Switch to Ruxolitinib Belumosudil Switch to Ruxolitinib
Other: Ruxolitinib Switch to Belumosudil Group Participants with breakthrough hepatic cGVHD on stable ruxolitinib therapy for non-hepatic cGVHD who develop new-onset hepatic cGVHD or have no response/progression on ruxolitinib, not attributable to other etiologies, and with no prior belumosudil exposure, will discontinue ruxolitinib and cross over to belumosudil.	Drug: Ruxolitinib Switch to Belumosudil Ruxolitinib Switch to Belumosudil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (ORR) for Hepatic cGVHD at Week 24 Time Frame: at Week 24 after treatment	at Week 24 after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Best overall response (BOR) Time Frame: Assessed continuously throughout the study from the date of randomization，up to 24 weeks after treatment	Assessed continuously throughout the study from the date of randomization，up to 24 weeks after treatment
Duration of response (DOR) Time Frame: From first response to progression/death, whichever came first, assessed up to 2 years after the date of randomization	From first response to progression/death, whichever came first, assessed up to 2 years after the date of randomization
Incidence of adverse events (AEs) Time Frame: Continuous monitoring from first dose to 30 days after last dose	Continuous monitoring from first dose to 30 days after last dose
Quality of life (QoL) score Time Frame: Assessed at baseline, Week 12, Week 24, and end of treatment	Assessed at baseline, Week 12, Week 24, and end of treatment
Overall survival (OS) Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 2 years after the date of randomization.	From date of randomization until the date of death from any cause, whichever came first, assessed up to 2 years after the date of randomization.
Failure-free survival (FFS) Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the date of randomization.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the date of randomization.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital of Zhejiang University

Collaborators

Peking University People's Hospital

Tongji Hospital

Ruijin Hospital

The First Affiliated Hospital of Zhengzhou University

First Affiliated Hospital of Ningbo University

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

April 1, 2030

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

August 25, 2026

First Submitted That Met QC Criteria

August 28, 2026

First Posted (Actual)

August 31, 2026

Study Record Updates

Last Update Posted (Actual)

August 31, 2026

Last Update Submitted That Met QC Criteria

August 28, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

BR-HEP-CGVHD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Belumosudil Versus Ruxolitinib for Steroid-Refractory or Breakthrough Hepatic cGVHD