UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC) FOR THE TREATMENT OF SEVERE (GRADE III-IV) STEROID-RESISTANT GRAFT VERSUS HOST DISEASE (GvHD): A PHASE I/II TRIAL
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 47
- 试验地点
- 8
- 主要终点
- vital parameters
研究概览
简要总结
MESENCHYMAL STROMAL CELLS (MSC) have shown promising albeit not always consistent therapeutic effects in the treatment of severe steroid-resistant acute Graf versus Host Disease. Remarkably, in all reported clinical studies the toxicity of Mesenchymal stromal cells administration has been found consistently negligible. The investigators believe that Umbilical Cord (UC) derived Mesenchymal stromal cells may represent a stronger immunosuppressive tool for such clinical emergency and no data suggest any change in the safety profile of these cells. For this reason, and in the best interest of the patient, the investigators plan to test the safety and activity of Umbilical Cord Mesenchymal stromal cells when given sequentially to another partially effective treatment of steroid resistant acute graf versus host disease such as Pentostatin.
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
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients are required to meet the following inclusion criteria:
- •Patients with steroid refractory grade III-IV classic acute graft versus host disease (GvHD)occurring within 100 days after transplant or induced by donor lymphocyte infusions (DLI) or T-cell add back. Steroid refractory graft versus host disease (GvHD)is defined according to Pidala and Anasetti10 as follows: a) progression of at least 1 overall grade within 3 days of optimal steroid treatment; b) failure to demonstrate any overall grade improvement over 5 to 7 days; c) incomplete response by 14 days of 2 mg/kg/day of steroid therapy.
- •Patients with persistent, recurrent, or late acute graft versus host disease (GvHD) (features of acute graft versus host disease occurring beyond 100 days, often during withdrawal of immune suppression).
- •Patients with an overlap syndrome in which diagnostic or distinctive features of chronic graft versus host disease (GvHD) and acute graft versus host disease (GvHD) appear together79.
排除标准
- •1. Inability to obtain written informed consent
研究组 & 干预措施
Umbilical Cord Mesenchymal stromal cells (UC-MSC)
Pentostatin will be given by intravenous infusion at a dose of 1 mg/m2 for 3 consecutive days. Thereafter, three Umbilical Cord Mesenchymal stromal cells (UC-MSC) infusions will be given at weekly interval starting from day 5. We will follow a dose escalating programme with progressively increasing doses of cells until the maximally tolerated dose (MTD) is achieved.
The dose escalating design will be characterised by the administration of 1x106 /kg UC-MSC per dose per three doses for the first three patients (total up to 3x106/kg). The second three patients will receive 2x106/kg UC-MSC per dose per three doses (total up to 6x106/kg). The third three patients will receive 3x106/kg UC-MSC per dose per three doses (total up to 9x106 cells/kg).
Since three dosages of cells are programmed for each group of 3 patients, a minimum of 9 patients should be studied, unless unacceptable acute infusion related toxicity is observed.
干预措施: UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC) (Biological)
结局指标
主要结局
vital parameters
时间窗: one year
Following infusion of UC-MSC, the patient will be monitored for acute infusion-related toxicity. Any toxicity will be treated at the discretion of the attending physician. Infusional toxicity is defined as any alteration of the vital parameters of the patient if they have appeared acutely and may be directly correlated to the UC-MSC infusion
次要结局
- assessed of acute graft versus host disease (GvHD)(one year)
研究者
Rambaldi Alessandro
Head Hematology and Bone Marrow Transplant Unit
A.O. Ospedale Papa Giovanni XXIII