A Prospective Multicenter, Single-arm Clinical Study of Anti-CD25 Monoclonal Antibody Combined With Ruxolitinib in the Treatment of Grade 3-4 Steroid-resistant Acute Graft-versus-host Disease
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 50
- 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 recognized first-line treatment for grade 3-4 aGVHD is systemic glucocorticoid. However, there is no recognized second-line treatment for grade 3-4 steroid-resistant aGVHD (SR-aGVHD). The investigators try to observe the efficacy and safety of early application of anti-CD25 monoclonal antibody(basiliximab) combined with ruxotilinib in the treatment of severe SR-aGVHD.
详细描述
Adults ages 18-65 with grade 3-4 SR-aGVHD
Design
Participants with grade 3-4 steroid-refractory acute GVHD (progression after 3 days or lack of improvement after 5 days of 1.5-2 mg/kg/d systemic steroids) receive combined therapy of basiliximab and ruxolitinib.
Basiliximab is given 20mg twice a week for week 1, and then once a week until GVHD of the participants reaches grade 1(3 episodes for minimum).
Ruxolitinib is given 5mg twice a day for one day and then escalates to 10mg twice a day if the participant is not administered with triazole antifungal agent.
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 primary 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).
- •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.
- •Ecg: QT interval > 450 ms.
- •Allergic to arsenic agent.
- •Pregnant or lactating women.
- •Expected survival <60 days.
- •Undergoing other drug clinical trials.
研究组 & 干预措施
ruxolitinib+basiliximab
Patients with grade 3-4 steroid-refractory aGVHD receive combined therapy of basiliximab and ruxolitinib.
干预措施: Ruxolitinib (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
- OS(through study completion, an average of 1year)
- EFS(through study completion, an average of 1year)
- Time to response(through study completion(median 12 days according to previous study))
- incidence rate of secondary grade 3-4 liver aGVHD(through study completion, an average of 1 year)
- ORR at d14/d56(day 14, day 56)
- Duration of response(through study completion, an average of 1year)
- incidence rated of chronic GVHD(through study completion, an average of 1 year)
研究者
Xuefeng He
chief physician
The First Affiliated Hospital of Soochow University