Clinical trial NCT04061876: First Line Therapy for High Risk Acute GVHD
Official title: Ruxolitinib in Combination With Corticosteroid as First Line Therapy for the Treatment of High Risk Acute Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: aGVHD
Stem Cell Transplant Complications
Keywords: aGVHD
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
Collaborators: name: LU DAOPEI MEDICAL
name: 960th Hospital of PLA
name: The Second Hospital of Hebei Medical University
name: The Second Affiliated Hospital of Dalian Medical University
name: Air Force Military Medical University, China
First posted: 2019-08-20
Enrollment: 198
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 )

Detailed 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.

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\~IV aGVHD or intermediate or high risk aGVHD (based on ST2, REG3a, other experimental objects) 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:

    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.
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.

Primary outcomes:
measure: Overall response rate (ORR) at Day 28
timeFrame: Day 28 after treatment
Secondary outcomes:
measure: Six-month duration of response
timeFrame: Six-month after treatment
measure: Duration of response
timeFrame: Day 90 after treatment
measure: Nonrelapse mortality (NRM)
timeFrame: 2 years after treatment
measure: Relapse rate
timeFrame: 2 years after treatment
measure: Disease-free survival (DFS)
timeFrame: 2 years after treatment
measure: Overall survival (OS)
timeFrame: 2 years after treatment
measure: GVHD-free and relapse-free survival (GRFS)
timeFrame: 2 years after treatment
measure: recurrence of aGVHD
timeFrame: 1 years after treatment
measure: Failure-free survival
timeFrame: 2 years after treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chines PLA General Hospital
name: Daihong Liu
role: STUDY_DIRECTOR
References:
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