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Clinical Trial NCT07184853 (RESCUE) for Graft vs Host Disease is recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here. | ||
Ruxolitinib Plus Etanercept vs Ruxolitinib for Steroid-Refractory Severe Acute GVHD (RESCUE) 122 Randomized Observational Overall Survival Short-Term
Acute graft-versus-host disease (aGVHD) is one of th...
Show MoreProspective Multicenter Randomized Study of Ruxolitinib Plus Etanercept vs Ruxolitinib Alone for Corticosteroid-Refractory Severe Acute GVHD After Allogeneic HSCT
- RESCUE
- Rux-Eta-SR-aGVHD
Etanercept
JAK1/2 inhibitor
TNF-α inhibitor
Corticosteroid-refractory GVHD
Severe aGVHD
Allo-HSCT complications
Graft-versus-Host Disease treatment
Immunosuppression
| Participant Group/Arm | Intervention/Treatment |
|---|---|
Active ComparatorRuxolitinib 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. | 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. |
ExperimentalRuxolitinib 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 st...Show More | 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. 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. |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
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. | From date of treatment initiation to Day 28. |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Durable Overall Response at Day 56 | Proportion of patients who achieved a response at day 28 and maintained the same response at day 56. | From date of treatment initiation to 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 | From date of treatment initiation to the earliest of loss of response (per MAGIC criteria), initiation of new systemic therapy for aGVHD, or death; assessed up to 24 weeks after treatment initiation. |
Best Overall Response (BOR) | Proportion of patients achieving CR or PR at any time up to day 28, without requiring new systemic immunosuppressive therapy. | From date of treatment initiation through Day 28. |
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. | From date of treatment initiation until event, assessed up to 24 weeks. |
Overall Survival (OS) | Time from treatment initiation until death from any cause. | From date of treatment initiation until death, assessed up to 2 years. |
Non-Relapse Mortality (NRM) | Death without relapse or progression of underlying hematologic disease. | From date of treatment initiation until non-relapse death, assessed up to 2 years. |
Cumulative Incidence of Relapse (CIR) | Relapse or progression of the underlying hematologic disease. | From date of treatment initiation until relapse/progression, assessed up to 2 years. |
Corticosteroid Use | Assessment of corticosteroid dose reduction and tapering patterns. | From date of treatment initiation, assessed up to 24 weeks. |
Incidence of Chronic GVHD | Cumulative incidence of chronic GVHD or overlap syndrome after study treatment. | From date of treatment initiation, assessed up to 2 years. |
Safety and Tolerability | Incidence, severity, and duration of adverse events (AEs) and serious adverse events (SAEs), including infections and secondary malignancies, assessed according to CTCAE v5.0. | From treatment initiation until 30 days after the end of study treatment. |
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.
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.
First Affiliated Hospital of Zhejiang UniversityZhejiang