Combining ruxolitinib with corticosteroids for severe acute graft‑versus‑host disease

Prospective Randomized Controlled Trial of Novel Therapies for Severe Acute GVHD (Graft-versus-host Disease)

This trial tests whether adding ruxolitinib to corticosteroids as first‑line treatment helps people who develop severe acute graft‑versus‑host disease after a first stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: Ruxolitinib
• Locations: 1 site (Beijing)
• Trial ID: NCT07509749 on ClinicalTrials.gov

What this trial studies

This is a Phase 2 interventional study testing combined ruxolitinib plus methylprednisolone versus methylprednisolone alone as first‑line therapy for severe acute GVHD occurring within 100 days after a first allogeneic hematopoietic stem cell transplant. Eligible participants have hematologic diseases and new‑onset severe acute GVHD; major exclusions include prior second transplant, overlap GVHD, uncontrolled infection, significant organ dysfunction, pregnancy, or very low blood counts. The study will administer the assigned treatment and monitor clinical response and adverse events to determine safety and efficacy signals. Outcomes will focus on response rates to primary therapy and treatment‑related toxicities during follow‑up.

Who should consider this trial

Good fit: Ideal candidates are people with hematologic diseases who developed new severe acute GVHD within 100 days of their first allo‑HSCT and meet laboratory and infection criteria for safe participation.

Not a fit: Patients with a second allogeneic transplant, overlap GVHD syndrome, active uncontrolled infections, significant renal dysfunction, very low neutrophil or platelet counts, pregnancy or breastfeeding are unlikely to be eligible and may not benefit.

Why it matters

Potential benefit: If successful, the combination could improve initial response rates and potentially survival for patients with severe acute GVHD when started as first‑line therapy.

How similar studies have performed: Ruxolitinib has shown benefit in prior trials for steroid‑refractory acute GVHD, but its use as initial first‑line therapy is less well established.

Eligibility criteria

Inclusion Criteria:

1. diagnosed with hematological diseases.
2. Have undergone first allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor source using bone marrow, peripheral blood stem cells, or cord blood for hematologic malignancies.
3. New onset of severe acute GVHD within 100 days post-transplantation.

Exclusion Criteria:

1. Recipients of second allogeneic stem cell transplant.
2. Acute GVHD induced by donor lymphocyte infusion, interferon.
3. Received first line aGVHD treatment before enrollment.
4. Overlap GVHD syndrome.
5. Pregnant or breast-feeding women.
6. Absolute neutrophil count (ANC) \<0.5×10e9/L or platelet count (PLT) \< 20×10e9/L.
7. Serum creatinine \> 2.0 mg/dL or creatinine clearance \< 40 mL/min measured or calculated by Cockroft-Gault equation.
8. Uncontrolled infection.
9. Human immunodeficiency virus infection.
10. Active hepatitis b virus, hepatitis C virus infection and need antivirus treatment.
11. Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed, or graft rejection.
12. Allergic history to Janus kinase inhibitors.
13. Severe organ dysfunction unrelated to underlying GVHD, including:

(1)Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).

(2)Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy.

(3)Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.

14.Received Janus kinase inhibitor therapy after allo-HSCT for any indication. 15.Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.

Where this trial is running

Beijing

• Department of Hematology, the Fifth Center of Chinese PLA General Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Daihong Liu

Conditions GVHD, Acute; Stem Cell Transplant Complications; acute graft-versus-host disease; Ruxolitinib; first line therapy