Belumosudil Versus Ruxolitinib for Steroid-Refractory or Breakthrough Hepatic cGVHD

Summary

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.

Conditions

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

Interventions

DRUG

Ruxolitinib treatment

Ruxolitinib treatment

DRUG

Belumosudil treatment

Belumosudil treatment

DRUG

Belumosudil Switch to Ruxolitinib

Belumosudil Switch to Ruxolitinib

DRUG

Ruxolitinib Switch to Belumosudil

Ruxolitinib Switch to Belumosudil

Sponsors & Collaborators

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

  collaborator OTHER

• The First Affiliated Hospital of Zhengzhou University

  collaborator OTHER

• Ruijin Hospital

  collaborator OTHER

• Tongji Hospital

  collaborator OTHER

• Peking University People's Hospital

  collaborator OTHER

• First Affiliated Hospital of Ningbo University

  collaborator NETWORK

• First Affiliated Hospital of Zhejiang University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-01

Primary Completion

2030-04-01

Completion

2030-12-31

Countries

• China

Study Locations