First-line ruxolitinib plus corticosteroids for grade II acute graft-versus-host disease

Novel First-line Therapies for Grade II Acute GVHD: a Randomized Controlled Trial

This trial will test whether adding ruxolitinib to standard corticosteroids helps people with new grade II acute graft-versus-host disease after an allogeneic stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 168 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: Ruxolitinib
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07340723 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional trial gives participants a combination of ruxolitinib and systemic corticosteroids as first-line therapy for grade II acute graft-versus-host disease occurring within 100 days after an allogeneic stem cell transplant. Eligible participants are those with hematologic disease who had a first allo-HSCT and present with new onset grade II or intermediate/high-risk aGVHD by modified Glucksberg criteria. The study will monitor clinical response rates and safety outcomes—including infections and organ function—while following participants through the acute treatment period. The goal is to determine whether the combination improves initial response and prevents progression compared with historical steroid-alone outcomes.

Who should consider this trial

Good fit: Ideal candidates are people who underwent a first allogeneic hematopoietic stem cell transplant for a hematologic disease and develop new grade II acute GVHD within 100 days who have not yet received first-line aGVHD treatment and meet organ-function and infection-screening requirements.

Not a fit: Patients unlikely to benefit include recipients of a second transplant, those with overlap GVHD, prior first-line aGVHD therapy before enrollment, uncontrolled infections, significant renal impairment, active untreated hepatitis or HIV infection, or who are pregnant or breastfeeding.

Why it matters

Potential benefit: If successful, combining ruxolitinib with corticosteroids could increase initial response rates and reduce progression to more severe GVHD, potentially improving survival and reducing steroid-related toxicity.

How similar studies have performed: Ruxolitinib has shown clear benefit for steroid-refractory aGVHD in prior studies, but its use combined with steroids as a first-line approach is less established and is being actively tested.

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 grade II acute GVHD or intermediate or high risk aGVHD (based on modified GVHD Glucksberg criteria) 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. Pregnant or breast-feeding women.
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, Beijing Municipality

• Department of Hematology, Senior Department of Hematology, The Fifth Medical Center of PLA General Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Liping Dou, M.D., Ph.D.

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