First Line Therapy for High Risk Acute GVHD

Chinese PLA General Hospital (301 Hospital)

Status and phase

Completed

Phase 2

Conditions

aGVHD

Stem Cell Transplant Complications

Treatments

Drug: Corticosteroid

Drug: Ruxolitinib

Study type

Interventional

Funder types

Other

Identifiers

NCT04061876

S2019-177-01

Details and patient eligibility

About

The purpose of this study is to determine the efficacy and safety of combined Ruxolitinib With Corticosteroids as First Line Therapy for the Treatment of High risk aGVHD(acute graft-versus-host disease )

Full description

Acute graft-versus-host disease (aGVHD) is treated with systemic corticosteroid immunosuppression as first line therapy. Many patients with high risk aGVHD do not respond to primary therapy, high-dose systemic corticosteroids; therefore, survival for those patients remains particularly poor. Here we determine the efficacy and safety of combined Ruxolitinib With Corticosteroids as First Line Therapy for the Treatment of High risk aGVHD.

Enrollment

198 patients

Sex

All

Ages

14 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

diagnosed with hematological diseases.
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.
new onset of grade II~IV aGVHD or intermediate or high risk aGVHD (based on ST2, REG3a, other experimental objects) within 100 days post-transplantation.

Exclusion criteria

recipients of second allogeneic stem cell transplant.
acute GVHD induced by donor lymphocyte infusion, interferon.
received first line aGVHD treatment before enrollment.
overlap GVHD syndrome.
pregnant or breast-feeding women.
absolute neutrophil count (ANC) <0.5×10e9/L or platelet count (PLT) < 20×10e9/L
Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation.
uncontrolled infection
human immunodeficiency virus infection
active hepatitis b virus, hepatitis C virus infection and need antivirus treatment.
Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed, or graft rejection.
allergic history to Janus kinase inhibitors.
Severe organ dysfunction unrelated to underlying GVHD, including:

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

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.

Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
Received Janus kinase inhibitor therapy after allo-HSCT for any indication.
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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

198 participants in 2 patient groups

Ruxolitinib combined with Corticosteroids

Experimental group

Description:

Participants began oral administration of ruxolitinib at 5 mg QD; Methylprednisolone: 1mg/kg/d , iv or iv gtt for at leas 5 days, then taper according to the clinical response.

Treatment:

Drug: Ruxolitinib

Drug: Corticosteroid

Corticosteroids

Active Comparator group

Description:

Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response.

Treatment:

Drug: Corticosteroid