Vedolizumab, Anti-CD25 Antibody Combined With Rapid Reduction of Glucocorticoids as Treatment of Grade 3-4 Steroid-resistant Acute Graft-versus-host Disease With Lower Gastrointestinal Involvement
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- overall response rate at day 28
研究概览
简要总结
Acute graft-versus-host disease (aGVHD) is the most common life-threatening complication of allogeneic hematopoietic stem cell transplantation. The investigators try to observe the efficacy and safety of application of vedolizumab, anti-CD25 monoclonal antibody and rapid reduction of glucocorticoids in the treatment of grade 3-4 steroid-refractory aGVHD(SR-aGVHD) with lower gastrointestinal involvement.
详细描述
Sample size: According to Simon optimal two-stage design, P0=60%, P1=80%, α=0.05, β=0.2, a sample size of 45 was chosen.
Objects: Adults ages 18-65 diagnosed with grade 3-4 SR-aGVHD with lower gastrointestinal involvement.
Design
Participants with grade 3-4 SR-aGVHD with lower gastrointestinal involvement(progression after 3 days or lack of improvement after 5 days of 1-2 mg/kg/d systemic steroids) receive combined therapy of vedolizumab and anti-CD25 monoclonal antibody, with methylprednisolone terminated in 7-10 days.
Vedolizumab is given 300mg, day 1/15/43, and then once every 8 weeks until gastrointestinal GVHD reaches grade 1 (1 episodes for minimum).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of grade 3-4(according to MAGIC criteria) steroid-resistant acute graft-versus-host disease(progression after 3 days or lack of improvement after 5 days of systemic 1.5-2 mg/kg steroids) with gastrointestinal involvement.
- •ECOG score≤
- •Must be able to understand and willing to participate in the study and sign the informed consent.
排除标准
- •Refractory/secondary graft-versus-host disease.
- •Severe complications such as myocardial infarction, chronic cardiac insufficiency,
- •hepatic failure, renal insufficiency, etc.
- •Clinically uncontrolled active infections.
- •Other Malignant tumors with progression.
- •Heart failure: EF<30%, NYHA≥grade III.
- •Pregnant or lactating women.
- •Expected survival <60 days.
- •Undergoing other drug clinical trials.
研究组 & 干预措施
vedolizumab+basiliximab
Patients with steroid-refractory aGVHD with gastrointestinal involvement receive combined therapy of vedolizumab and basiliximab.
干预措施: Basiliximab (Drug)
vedolizumab+basiliximab
Patients with steroid-refractory aGVHD with gastrointestinal involvement receive combined therapy of vedolizumab and basiliximab.
干预措施: Vedolizumab (Drug)
结局指标
主要结局
overall response rate at day 28
时间窗: day 28
The primary endpoint is the overall response rate (ORR) at day 28 defined as proportion of patients demonstrating partial (PR) or complete response (CR) without requirement for additional systemic immunosuppressive therapy (IST) at day 28 after second-line treatment initiates.
次要结局
- EFS(through study completion, an average of 1year)
- ORR at d14/d56(day 14, day 56)
- OS(through study completion, an average of 1year)
- Duration of response(through study completion, an average of 1year)