This is a prospective, multicenter, randomized controlled trial designed to evaluate whether the combination of ruxolitinib and etanercept provides superior efficacy compared with ruxolitinib monotherapy in patients with severe corticosteroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Acute graft-versus-host disease (aGVHD) is one of the most common and life-threatening complications following allo-HSCT. Although corticosteroids remain the standard first-line treatment, many patients do not respond adequately. For patients with severe steroid-refractory aGVHD, the prognosis is extremely poor, with high short-term mortality and very low long-term survival.
Ruxolitinib, a JAK1/2 inhibitor, has been approved for the treatment of SR-aGVHD, but response rates remain suboptimal, particularly in patients with gastrointestinal involvement. Etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, has shown activity in GVHD by targeting inflammatory pathways. Previous observational studies from our center suggested that combining ruxolitinib with etanercept may improve response rates, especially in gastrointestinal and hepatic GVHD, without significantly increasing relapse risk.
In this trial, approximately 122 patients with grade III-IV SR-aGVHD will be randomized 1:1 to receive either ruxolitinib alone or ruxolitinib plus etanercept. The primary endpoint is the overall response rate (ORR) at day 28. Secondary endpoints include durable response, best overall response, failure-free survival, overall survival, cumulative incidence of relapse, non-relapse mortality, incidence of chronic GVHD, and safety outcomes.
This study seeks to provide new clinical evidence for an optimized treatment strategy for patients with severe SR-aGVHD, aiming to improve outcomes in this high-risk population.
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Parallel
Ruxolitinib (JAKAVI®)
DrugRuxolitinib will be administered orally at a dose of 10 mg twice daily (approximately every 12 hours), with or without food. Dose modifications are allowed according to protocol-defined safety and efficacy criteria. Ruxolitinib may be continued for up to 24 weeks, with tapering guided by patient response and GVHD status.
Etanercept (Enbrel)
DrugEtanercept will be administered as a subcutaneous injection at a dose of 25 mg twice weekly for 4 weeks (total 8 doses). For patients with partial response at day 28, treatment may be extended once weekly for an additional 2-4 weeks at the investigator's discretion.
Overall Response Rate (ORR) at Day 28
Proportion of patients achieving complete response (CR) or partial response (PR) compared with baseline organ staging, as assessed by MAGIC criteria.
Durable Overall Response at Day 56
Proportion of patients who achieved a response at day 28 and maintained the same response at day 56.
Duration of Response (DOR)
From first documented response until progression of aGVHD or initiation of new systemic therapy for aGVHD, assessed up to 24 weeks
Best Overall Response (BOR)
Proportion of patients achieving CR or PR at any time up to day 28, without requiring new systemic immunosuppressive therapy.
Failure-Free Survival (FFS)
Time from treatment initiation to relapse/progression of underlying hematologic disease, non-relapse mortality, or initiation of new systemic therapy for aGVHD.
Exploratory Biomarker Analyses
Evaluation of serum biomarkers (e.g., TNFR1) and other molecular correlates associated with response to treatment.
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First Affiliated Hospital of Zhejiang University
Lead sponsor
The First Affiliated Hospital of Zhengzhou University
Collaborator
Tongji Hospital
Collaborator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Collaborator
The Children's Hospital of Zhejiang University School of Medicine
Collaborator
Ruijin Hospital
Collaborator
