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

Sponsor
First Affiliated Hospital of Zhejiang University
Study ID
NCT07184853
Status
Recruiting
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Conditions

  • Graft vs Host Disease

Eligibility Criteria

Sex
ALL
Age
12 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Ruxolitinib (JAKAVI®) — DRUG
    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.
  • Etanercept (Enbrel) — DRUG
    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.

Study Details

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.

Key Dates

Start date
Sep 25, 2025
Status verified
Sep 2025
Primary completion
Sep 25, 2027
Completion
Sep 25, 2028

Study Design

Enrollment
122 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Ruxolitinib Monotherapy
    Participants will receive ruxolitinib (10 mg orally twice daily, approximately every 12 hours, with or without food). Treatment will continue for up to 24 weeks. Dose reductions or discontinuation may occur according to protocol-defined safety and response criteria. Corticosteroid tapering will follow study guidelines.
  • Experimental: Ruxolitinib Plus Etanercept
    Participants will receive ruxolitinib (10 mg orally twice daily, approximately every 12 hours, with or without food) combined with etanercept (25 mg subcutaneous injection, twice weekly for 4 weeks, total 8 doses). Etanercept may be extended for an additional 2-4 weeks at investigator's discretion for patients with partial response. Treatment with ruxolitinib may continue for up to 24 weeks, with dose tapering per study protocol. Corticosteroid tapering will follow study guidelines.

Primary Outcome Measure

Overall Response Rate (ORR) at Day 28 [ Time Frame: From date of treatment initiation to Day 28. ]

Central Contacts

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