Chronic Graft-Versus-Host Disease, Graft vs Host Disease
Conditions
Brief summary
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.
Interventions
DRUGMadecassoside Tablets
Madecassoside tablets will be administered orally at a dose of 0.2 g (2 tablets) three times daily for 6 months in combination with standard therapy.
DRUGStandard Therapy
Standard therapy may include corticosteroids, calcineurin inhibitors, ruxolitinib, belumosudil, topical medications, and supportive care according to institutional guidelines and physician discretion.
Sponsors
WeiShi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Skin and/or Joint/Fascia NIH cGVHD Scores | 6 months | The proportion of participants achieving complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) in skin and/or joint/fascia manifestations according to the 2014 NIH chronic graft-versus-host disease response criteria after 6 months of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall cGVHD Response Rate | 6 months | Overall response rate of chronic graft-versus-host disease based on the 2014 NIH response criteria. |
| Failure-Free Survival | 2 years | Failure-free survival defined as survival without relapse, non-relapse mortality, or addition of new systemic therapy. |
| Non-Relapse Mortality | 2 years | Incidence of death without relapse of the underlying disease during follow-up. |
| Corticosteroid Dose Reduction | 6 months | Proportion of participants achieving at least 50% reduction or discontinuation of corticosteroid therapy. |
| Patient-Reported Outcomes | Baseline to 6 months | Changes in patient-reported outcomes including Lee Symptom Scale (LSS), Scleroderma Health Assessment Questionnaire (SHAQ), and Photographic Range of Motion (P-ROM) scores. |
| Traditional Chinese Medicine Symptom Score | Baseline to 6 months | Changes in Traditional Chinese Medicine symptom scores during treatment. |
| Safety and Adverse Events | Up to 2 years | Incidence and severity of adverse events assessed according to CTCAE version 5.0. |
Countries
China
Contacts
CONTACTwei MD, PhD
Outcome results
None listed