Phase I- II Study of in Vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus With or Without Vidaza (Azacitidine) for the Treatment of Steroid-refractory Acute Graft-versus-host Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Response Rate of Patients With Steroid-refractory Graft-versus-host Disease (GVHD) Using Cyclophospahmide and Sirolimus Combined With 3 Variations of Low-dose IL 2 and Low-dose Vidaza.
研究概览
简要总结
In this study the investigators are proposing to treat patients with steroid-refractory Graft-versus-host Disease (GVHD) stabilization using IL-2 and azacitidine
详细描述
High-dose cyclophosphamide and sirolimus have been successfully used for the prevention of Graft-versus-host Disease (GVHD) and have shown to enhance the Tregs subpopulation. The addition of low dose IL-2 and a demethylating agent such as azacitidine will also be studied in an attempt to promote and stabilize the FoxP3 expression of Tregs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a documented clinical diagnosis of grade II-IV acute graft-versus- host disease defined as graft versus host disease (GVHD) occurring within the first 100 days of transplantation
- •Patients must be steroid-refractory defines as progression after 3 days of corticosteroid therapy or no response after 5 days of corticosteroid therapy.
- •Progression is defined as up-grading
- •No response is defined as no down-grading
- •Progression after 3 days requires patients to have received at least 2 mg/mg/day for a total of 6 mg/kg of methylprednisolone or its equivalent.
- •No response after 5 days requires patient to have received at least 2 mg/kg/d for a total of 10 mg/kg of methylprednisolone or its equivalent.
- •Patients with exacerbation of GVHD during steroid taper will require re-treatment with 2mg/kg/d of corticosteroids and will need to meet the criteria
- •Age 18-70
- •Patients must have received an allogeneic hematopoietic stem cell transplant within 100 days of study enrollment.
- •Serum creatinine < 2 mg/dL
排除标准
- •Patients cannot have active central nervous system (CNS) disease.
- •Patients must not have received cyclophosphamide for GVHD prophylaxis
- •Patients must not have pneumonia requiring oxygen supplementation
- •Unable or unwilling to sign informed consent.
研究组 & 干预措施
Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus
Lowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) & Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).
干预措施: Low dose IL-2, Vidaza, Cytoxan & Sirolimus (Drug)
Lowdose IL-2, Cytoxan + Sirolimus
Low dose IL-2 with Cytoxan + Sirolimus Patients in treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus.
干预措施: Low dose IL-2 with Cytoxan + Sirolimus (Drug)
Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus
Lowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) & Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).
干预措施: Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus (Drug)
Cyclophosphamide and Sirolimus
cyclophosphamide and sirolimus combo
干预措施: Cyclophosphamide and Sirolimus (Drug)
结局指标
主要结局
Response Rate of Patients With Steroid-refractory Graft-versus-host Disease (GVHD) Using Cyclophospahmide and Sirolimus Combined With 3 Variations of Low-dose IL 2 and Low-dose Vidaza.
时间窗: 28 days to 100 days post transplant
The primary objective of this study is to determine the response rate of patients treated steroid-refractory graft-versus-host disease (GVHD) using cyclophospahmide and sirolimus combined with 3 variations of low-dose IL 2 and low-dose Vidaza with an outcome goal of promoting CD4+CD25+FoxP3+ Tregs.
次要结局
未报告次要终点