A Study of T-Cell Replete, HLA-Mismatched Haploidentical Bone Marrow Transplantation With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia Lacking HLA-Matched Related Donor
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant
研究概览
简要总结
Severe aplastic anemia is a rare and serious form of bone marrow failure related to an immune-mediated mechanism that results in severe pancytopenia and high risk for infections and bleeding. Patients with matched sibling donors for transplantation have a 80-90% chance of survival; however, a response rate with just immunosuppression for those patients lacking suitable HLA-matched related siblings is only 60%. With immunosuppression, only 1/3 of patients are cured, 1/3 are dependent on long term immunosuppression, and the other 1/3 relapse or develop a clonal disorder. Recent studies have shown that using a haploidentical donor for transplantation has good response rates and significantly lower rates of acute and chronic GVHD.
详细描述
Mismatched haploidentical donors will be identified for patients with severe aplastic anemia. These patients will undergo a preparative regimen of Fludarabine/Cyclophosphamide/TBI followed by haploidentical bone marrow transplantation. Post-transplant Cyclophosphamide will be administered on Days 3 & 4. Immunosuppression with Tacrolimus and MMF will begin on Day +5; MMF will be discontinued on Day +35 while Tacrolimus continues until Day +180. Investigators hypothesize that haploidentical transplantation with the above-mentioned preparative regimen will have a <30% graft failure rate. The one-sided exact Binomial test at 5% significance level will be used to test this hypothesis. The size of 20 patients provides the power of 92.5% for confirming the 30-day graft failure rate <30%.
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
- 1 Year 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor who must have negative HLA cross-match in the host vs. graft direction
- •Age <= 65 years for previously treated and <= 75 years for previously treated patients
- •KPS >= 70%
- •Aplastic Anemia that meets the following criteria:
- •Peripheral Blood (must fulfill 2 of 3):
- •<500 PMN/mm3
- •<20,000 platelets
- •absolute reticulocyte count <40,000/microL
- •Bone Marrow (must be either):
- •markedly hypocellular (<25% of normal cellularity)
- •moderately hypocellular with 70% non-myeloid precursors and patient meets peripheral blood criteria above
排除标准
- •poor cardiac function (LVEF <40%)
- •poor pulmonary function (FEV1 & FVC <50% predicted)
- •poor liver function (bili >= 2mg/dL)
- •poor renal function (creatinine >= 2.0mg/dL or creatinine clearance <40mL/min)
- •prior allogeneic transplant
研究组 & 干预措施
Flu/Cy/TBI
Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 & 4.
干预措施: Cyclophosphamide (Drug)
Flu/Cy/TBI
Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 & 4.
干预措施: Total Body Irradiation (Radiation)
Flu/Cy/TBI
Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 & 4.
干预措施: Fludarabine (Drug)
Flu/Cy/TBI
Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 & 4.
干预措施: Rabbit ATG (Drug)
结局指标
主要结局
Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant
时间窗: 2 years
Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be \<30%.
次要结局
- Determine the incidence of grade 2-4 and 3-4 acute graft versus host disease at 100 days post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course(2 years)
- Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points(2 years)
- Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events(2 years)
- Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course(2 years)