Ruxolitinib Plus Etanercept vs Ruxolitinib for Steroid-Refractory Severe Acute GVHD

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 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.

Conditions

• Graft vs Host Disease

Interventions

DRUG

Ruxolitinib (JAKAVI®)

Ruxolitinib 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.

DRUG

Etanercept (Enbrel)

Etanercept 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University

  collaborator OTHER

• Tongji Hospital

  collaborator OTHER

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  collaborator OTHER

• The Children's Hospital of Zhejiang University School of Medicine

  collaborator OTHER

• Ruijin Hospital

  collaborator OTHER

• First Affiliated Hospital of Zhejiang University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-25

Primary Completion

2027-09-25

Completion

2028-09-25

Countries

• China

Study Locations