Clinical trial NCT04397367: Low Dose Ruxolitinib in Combination With Methylprednisolone
Official title: Low Dose Ruxolitinib in Combination With Methylprednisolone 1mg/kg as Initial Therapy for Acute Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: aGVHD
Stem Cell Transplant Complications
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2020-05-21
Enrollment: 38
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is to determine the efficacy and safety of combined Low dose Ruxolitinib With Methylprednisone as Initial Therapy for the aGVHD(acute graft-versus-host disease )

Detailed description: Corticosteroid is used as a first-line treatment for acute GVHD. However, it is effective in only about half of patients. In this prospective study, the investigators prospectively combined low dose ruxolitinib and 1mg/kg methylprednisolone in the initial treatment of acute GVHD. In order to effectively control GVHD without exposing acute GVHD patients to more intense and prolonged immunosuppression, we used ruxolitinib (20mg/day, 10mg/day, 5mg/day, 2.5mg/day) combined with 1mg/kg methylprednisolone. To ally steroid-related complications, we decreased steroid exposure time (39 days) and cumulative methylprednisolone doses (15.4 mg/kg) to spare the associated toxicity of glucocorticoid therapy.

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 high risk aGVHD \[based on suppression of tumorigenicity 2 (also ST2), Regenerating Islet Derived Protein 3 Alpha (also REG3a), 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: complete remission rate of acute GVHD 28 days after enrollment.
timeFrame: Day 28 after treatment
Secondary outcomes:
measure: the incidence of relapsed acute GVHD
timeFrame: Day 90 after treatment
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: 6 months after treatment
measure: Relapse rate
timeFrame: 2 years after treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Daihong Liu
role: PRINCIPAL_INVESTIGATOR
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