Status:
RECRUITING
Ruxolitinib Plus Etanercept vs Ruxolitinib for Steroid-Refractory Severe Acute GVHD
Lead Sponsor:
First Affiliated Hospital of Zhejiang University
Collaborating Sponsors:
The First Affiliated Hospital of Zhengzhou University
Tongji Hospital
Conditions:
Graft vs Host Disease
Eligibility:
All Genders
12-70 years
Phase:
NA
Brief Summary
This is a prospective, multicenter, randomized controlled trial designed to evaluate whether the combination of ruxolitinib and etanercept provides superior efficacy compared with ruxolitinib monother...
Detailed Description
Steroid-refractory severe acute graft-versus-host disease (SR-aGVHD) remains a leading cause of early morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Although ruxolit...
Eligibility Criteria
Inclusion
- Received allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor source (matched sibling, matched unrelated, or haploidentical), using bone marrow, peripheral blood stem cells, or cord blood; conditioning regimen may be myeloablative, reduced-intensity, or non-myeloablative.
- Age between 12 and 70 years.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
- Clinical diagnosis of grade III-IV acute graft-versus-host disease (aGVHD) according to MAGIC criteria.
- Evidence of neutrophil and platelet engraftment prior to study treatment (absolute neutrophil count \>1,000/mm³ and platelet count ≥20,000/mm³ within 48 hours before study entry; growth factor support and transfusion permitted).
- Diagnosis of steroid-refractory aGVHD, defined as one of the following:
- Disease progression after 3-5 days of methylprednisolone 2 mg/kg/day (or equivalent).
- No improvement after 7 days of methylprednisolone 2 mg/kg/day (or equivalent).
- Progression from grade II to grade III-IV aGVHD after 3-5 days of methylprednisolone 1 mg/kg/day (or equivalent).
- Able to take oral medication.
- Expected survival \>8 weeks.
- Women of childbearing potential must have a negative serum β-HCG test prior to enrollment; both male and female participants of reproductive potential must agree to use effective contraception during the study and for 3 months after study completion.
- Voluntary written informed consent provided and ability to comply with study procedures.
Exclusion
- Prior systemic treatment for aGVHD other than corticosteroids with or without calcineurin inhibitors (CNI); prophylactic use of MTX, MMF, or CD25 monoclonal antibody is permitted.
- Clinical features consistent with de novo chronic GVHD or overlap syndrome (per Jagasia 2015).
- Uncontrolled active infection, including severe bacterial, fungal, viral, or parasitic infection. Patients on appropriate treatment without evidence of progression may be eligible.
- Evidence of active tuberculosis.
- Known HIV infection.
- Relapse of primary malignancy or post-transplant lymphoproliferative disorder.
- Severe respiratory disease, including mechanical ventilation or resting oxygen saturation \<90%.
- Renal dysfunction: serum creatinine \>2.0 mg/dL, requirement for dialysis, or creatinine clearance \<30 mL/min (Cockcroft-Gault).
- Active hepatitis B infection (HBsAg positive with HBV DNA ≥1×10³ IU/mL) or active hepatitis C infection (HCV antibody positive with detectable HCV RNA above normal).
- Clinically significant or uncontrolled cardiac disease, including recent myocardial infarction, uncontrolled hypertension, NYHA class III/IV heart failure, unstable angina, or clinically significant arrhythmia (e.g., sustained ventricular tachycardia, second- or third-degree AV block).
- Cholestatic disease or unresolved hepatic veno-occlusive disease not attributed to aGVHD.
- History of progressive multifocal leukoencephalopathy (PML).
- Prior exposure to JAK inhibitors after allo-HSCT.
- Participation in another investigational drug trial within 30 days or within 5 half-lives of the investigational drug (whichever is longer).
- Prior history of grade ≥3 non-hematologic adverse events attributable to ruxolitinib or etanercept.
- Any condition judged by the investigator to place the patient at undue risk or interfere with study participation.
- Known hypersensitivity or intolerance to systemic immunosuppressive agents.
- Pregnant or breastfeeding women.
Key Trial Info
Start Date :
September 25 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 25 2028
Estimated Enrollment :
122 Patients enrolled
Trial Details
Trial ID
NCT07184853
Start Date
September 25 2025
End Date
September 25 2028
Last Update
September 22 2025
Active Locations (1)
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1
The First Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China, 310000