A Prospective Study of Madecassoside Tablets in Sclerotic Chronic Graft-versus-Host Disease After Allo-HSCT

A Prospective, Multicenter, Single-Arm Phase 2 Study of Madecassoside Tablets Combined With Standard Therapy for Sclerotic Chronic Graft-versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Sclerotic chronic graft-versus-host disease (scl-cGVHD) is a severe subtype of chronic GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by skin sclerosis, fascial involvement, and restricted joint mobility, leading to substantial functional impairment and reduced quality of life. Current standard therapies, including corticosteroids and other immunosuppressive agents, have limited efficacy in patients with refractory or steroid-dependent disease.

Madecassoside tablets, a standardized extract of Centella asiatica, have demonstrated anti-inflammatory and anti-fibrotic properties in previous studies and may provide therapeutic benefit in fibrotic diseases.

This study is a prospective, multicenter, single-arm phase 2 clinical trial designed to evaluate the efficacy and safety of madecassoside tablets combined with standard therapy in patients with scl-cGVHD after allo-HSCT. Eligible participants will receive oral madecassoside tablets (0.2 g three times daily) in addition to standard treatment for 6 months. Clinical assessments will be performed at baseline and at weeks 4, 8, 12, and 24.

The primary endpoint is the improvement rate of skin and/or joint/fascia NIH cGVHD scores at 6 months according to the 2014 NIH consensus criteria. Secondary endpoints include overall cGVHD response rate, failure-free survival, non-relapse mortality, corticosteroid dose reduction, patient-reported outcomes, and safety assessments. Peripheral blood samples will also be collected to explore changes in inflammatory cytokines and lymphocyte subsets during treatment.

Inclusion Criteria:

1. Ability to understand and willingness to sign written informed consent;

2. Age 14 to 65 years;

3. Diagnosis of sclerotic chronic graft-versus-host disease (scl-cGVHD) according to the 2014 NIH consensus criteria, including superficial or deep skin sclerosis, fasciitis, or restricted joint mobility;

4. Prior treatment history meeting at least one of the following:

   • Received systemic corticosteroid therapy for ≥12 months and at least 1 additional systemic therapy; OR
   • Received corticosteroid therapy and at least 2 additional systemic therapies;

5. Karnofsky Performance Status (KPS) score ≥60;

6. Absolute neutrophil count >1,000/μL;

7. Platelet count ≥50,000/μL.

Exclusion Criteria:

• 1. Total bilirubin >1.5 times the upper limit of normal; 2. Creatinine clearance <30 mL/min; 3. Uncontrolled infection; 4. Uncontrolled cardiovascular or pulmonary disease; 5. Any clinical condition that, in the investigator's judgment, makes the participant unsuitable for study participation.