Low Dose Ruxolitinib in Combination With Methylprednisolone 1mg/kg as Initial Therapy for Acute Graft-Versus-Host Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- complete remission rate of acute GVHD 28 days after enrollment.
研究概览
简要总结
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 )
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 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.
排除标准
- •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.
研究组 & 干预措施
Ruxolitinib10 mg twice a day combined with Corticosteroids
Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 10 mg twice a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.
干预措施: Ruxolitinib 10 mg twice a day combined with Corticosteroids (Drug)
Ruxolitinib5 mg twice a day combined with Corticosteroids
Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 5 mg twice a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.
干预措施: Ruxolitinib 5 mg twice a day combined with Corticosteroids (Drug)
Ruxolitinib5 mg once a day combined with Corticosteroids
Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 5mg once a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.
干预措施: Ruxolitinib 5 mg once a day combined with Corticosteroids (Drug)
Ruxolitinib 2.5 mg twice a day combined with Corticosteroids
Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 2.5 mg once a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.
干预措施: Ruxolitinib 2.5 mg once a day combined with Corticosteroids (Drug)
结局指标
主要结局
complete remission rate of acute GVHD 28 days after enrollment.
时间窗: Day 28 after treatment
Defined as the proportion of participants demonstrating a complete response (CR), or partial response (PR) of acute GVHD
次要结局
- the incidence of relapsed acute GVHD(Day 90 after treatment)
- Six-month duration of response(Six-month after treatment)
- Duration of response(Day 90 after treatment)
- Nonrelapse mortality (NRM)(6 months after treatment)
- Relapse rate(2 years after treatment)
研究者
Daihong Liu
Director
Chinese PLA General Hospital