Overview

This study is a prospective, multicenter, open-label, phase II clinical trial designed to evaluate the safety and efficacy of moxibustion in patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

A total of 42 patients with SR-aGVHD, primarily involving the gastrointestinal tract and presenting with abdominal pain and diarrhea, will be enrolled. All participants will receive standard second-line therapy based on best available treatment (BAT), including ruxolitinib, basiliximab, or methotrexate, according to clinical judgment. In addition, patients will receive moxibustion at specific acupoints (Tianshu \[ST25\], Shenque \[CV8\], and Qihai \[CV6\]) for 30 minutes once or twice daily for 28 days.

The primary endpoint is the overall response rate (ORR) at Day 28. Secondary endpoints include durable ORR at Day 56, incidence and severity of chronic GVHD (cGVHD), non-relapse mortality (NRM), overall survival (OS), and changes in traditional Chinese medicine (TCM) syndrome scores. Safety will be assessed by monitoring adverse events throughout the study period.

This study aims to explore whether moxibustion, as an adjunctive therapy, can improve clinical outcomes and provide a safe and effective treatment strategy for patients with SR-aGVHD after allo-HSCT.

Eligibility

Inclusion Criteria:

• Participants must meet all of the following criteria:

Age 14 to 65 years, male or female. Underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of acute graft-versus-host disease (aGVHD) according to standard criteria, with gastrointestinal involvement (e.g., abdominal pain and diarrhea), and classified as grade II-IV.

Steroid-refractory or steroid-dependent aGVHD, defined as:

Disease progression within 3 days of systemic corticosteroid treatment, or No response within 7 days, or Failure to achieve complete response after 28 days of immunosuppressive therapy, or Recurrence or worsening during steroid tapering. Absolute neutrophil count ≥ 0.5 × 10⁹/L for at least 3 consecutive days. Traditional Chinese medicine (TCM) syndrome differentiation consistent with spleen-kidney yang deficiency.

Female participants of childbearing potential must have a negative pregnancy test at screening and agree to use effective contraception during the study.

Male participants must agree to use effective contraception during the study. Ability to understand and willingness to sign a written informed consent form. Willingness and ability to comply with study procedures and follow-up.

Exclusion Criteria:

• Participants meeting any of the following criteria will be excluded:

Prior treatment with ≥1 systemic therapy for aGVHD other than corticosteroids. Diagnosis of GVHD overlap syndrome according to NIH criteria. History of splenectomy after transplantation. Evidence of relapse of the underlying disease or receipt of anti-relapse therapy after transplantation.

Unresolved toxicities or complications from prior transplantation (excluding GVHD).

Prior moxibustion therapy after transplantation. Uncontrolled active infection. Known human immunodeficiency virus (HIV) infection. Active hepatitis B or C infection requiring treatment, or risk of HBV reactivation.

Receipt of other investigational therapy within 21 days prior to enrollment (or within 5 half-lives, whichever is longer).

Renal dysfunction: serum creatinine ≥ 2.0 mg/dL or creatinine clearance \< 40 mL/min.

Hepatic dysfunction unrelated to GVHD, including cholestatic disease or unresolved hepatic veno-occlusive disease.

Severe cardiovascular disease, including unstable angina, myocardial infarction within 6 months, NYHA class III-IV heart failure, or circulatory failure requiring vasoactive support.

Severe respiratory disease requiring mechanical ventilation or ≥50% oxygen support.

Use of high-dose corticosteroids (≥1 mg/kg/day methylprednisolone or equivalent) for non-GVHD indications within 7 days prior to enrollment.

Pregnant or breastfeeding women. Severe skin damage or known allergy/intolerance to study-related procedures. Any other condition that, in the investigator's judgment, would interfere with study participation.