Belumosudil Versus Ruxolitinib for Steroid-Refractory or Breakthrough Hepatic cGVHD

Sponsor
First Affiliated Hospital of Zhejiang University
Study ID
NCT07794514
Status
Recruiting
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Conditions

  • Belumosudil
  • Hematopoietic Stem Cell Transplantation (HSCT)
  • Hepatic cGVHD
  • Ruxolitinib
  • cGVHD

Eligibility Criteria

Sex
ALL
Age
12 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

First listed
Aug 31, 2026
Start date
Oct 1, 2026
Status verified
Aug 2026
Primary completion
Apr 1, 2030
Completion
Dec 31, 2030

Study Design

Enrollment
170 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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).
  • 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).
  • 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.
  • 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.

Primary Outcome Measure

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

Central Contacts

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