PhaseⅡTrial of Co-transplantation With Bone Marrow Derived Mesenchymal Stem Cells From Related Donors in Alternative Donor Transplantation of Severe Aplastic Anemia.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- survival rate
研究概览
简要总结
The study is a phase II trial designed to evaluate the efficacy and safety of co-transplantation with bone marrow derived mesenchymal stem cells from related donors in alternative donor transplantation of severe aplastic anemia.
详细描述
Aplastic anemia (AA) is an autoimmune hematologic stem cell disease mediated by activated T-lymphocytes that leads to bone marrow dysfunction. In the presence of an empty marrow, pancytopenia, and transfusion dependence, the severity of the disease is based on neutrophil (PMN) count: nonsevere AA (nSAA; PMN > 0.5 × 109/L), severe AA (SAA;PMN 0.2- 0.5 × 109/L), and very severe AA (vSAA; PMN< 0.2 × 109/L).
Allogeneic BMT from an HLA-identical sibling donor or matched-alternative donor is the treatment of choice for patients with aplastic anaemia.Transplantation for patients with severe aplastic anaemia from an HLA identical sibling donor is now very successful with a 75-90% chance of long term cure and with overall survival of between 65% and 73% at 5 years for matched-alternative donor transplantation. However, these two approachs are limited by the availability of HLA-matched donors.
Patients without HLA-identical sibling donor or matched-alternative donor can be offered immunosuppressive treatment (IST) involving injections of Anti-thymocyte globulin (ATG) in combination with cyclosporine (CsA). The treatment response with ATG is at best between 60-80%, 30%-40% patients relapse following an initial response to treatment. Moreover, a recent study has shown that on multivariate analysis of response at 6 months, only younger age, absolute reticulocyte count (ARC) and absolute lymphocyte count (ALC), correlate with response to ATG. Patients with SAA or vSAA, with much lower ARC and ALC, were poor response to IST and have high risks of dying of infection and bleeding.
Nowadays, with advances in transplant technology, HLA-mismatched related donors and unrelated donors transplantation has achieved good clinical results. Data from the XJ Huang indicated that patients with HLA-mismatched related donors achieved 100% donor myeloid engraftment and have a survival rate of 64.6±12.4%. Retrospectively analyzed results for 154 patients with acquired SAA who received BMT from unrelated donors identified through the Japan Marrow Donor Program showed the probability of OS at 5 years was 56% (95% confidence interval, 34%-78%).
Compared with malignant disease, mismatched related donor or unrelated donor HSCT for SAA involves distinct challenges mainly associated with high graft failure and high GVHD. So, if we can find a way to promote implantation meanwhile prevent or reduce GVHD , the efficacy of HLA-mismatched related donors transplantation can improve.
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
- 14 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In line with the 2009 Edition (United Kingdom) aplastic anemia diagnostic criteria for SAA or VSAA;
- •Age less than 50 years old,willing to transplant；
- •No HLA-identical sibling donor；
- •Have HLA-mismatched related donors or unrelated donors ( ≥5/10 HLA matched loci in related donors; ≥8/10 HLA matched loci in unrelated donors )
- •No serious infection or acute hemorrhage;
- •Cardiac ultrasound examination showed left ventricular ejection fraction is greater than 50%;
- •Both transaminase and serum creatinine level are no more than twice times the upper limit of normal value (ULN);
- •No acute infectious disease;
- •Ability to understand and the willingness to sign a written informed consent document.
- •ECOG score of 0-2 points.
排除标准
- •Patients with severe infection or active bleeding;
- •With severe cardiac insufficiency, left ventricular ejection fraction <50%;
- •With severe liver dysfunction, liver function (ALT and the TBIL) is higher than the ULN 3 times;
- •With severe renal insufficiency, renal function (Cr) is twice higher than the ULN; or 24-hour urine creatinine clearance rate (Ccr) lower than 50ml/min;
- •Active tuberculosis, severe acute hepatitis and other infectious diseases in active period;
- •ECOG score more than 3 points;
- •Accompanied by malignant tumors and other clonal disease;
- •Poor compliance and the researchers considered unsuitable for MSC infusion.
研究组 & 干预措施
Mesenchymal stem cells
Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with severe aplastic anemia.
干预措施: mesenchymal stem cells (Biological)
结局指标
主要结局
survival rate
时间窗: up to 2 years after HSCT
The 2-year disease-free survival and overall survival.
次要结局
- chronic GVHD(UP to 2 years after HSCT)
- Transplant-related mortality(UP to 1 months after HSCT)
- The implantation(Up to 4 weeks after HSCT)
- acute GVHD(UP to 3 months after HSCT)
- Rates of relapse(UP to 2 years after HSCT)
研究者
Yang Xiao
PhaseⅡtrial of co-transplantation with bone marrow derived mesenchymal stem cells from related donors in alternative donor transplantation of severe aplastic anemia.
Guangzhou General Hospital of Guangzhou Military Command