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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
170
Ruxolitinib treatment
Belumosudil treatment
Belumosudil Switch to Ruxolitinib
Ruxolitinib Switch to Belumosudil
The First Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGOverall Response Rate (ORR) for Hepatic cGVHD at Week 24
Time frame: at Week 24 after treatment
Best overall response (BOR)
Time frame: 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
Incidence of adverse events (AEs)
Time frame: 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
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.
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.
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