Reduced Intensity Allogeneic Transplantation For Severe Osteopetrosis Incorporating A Second Cd34 Selected Graft
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Number of Patients Achieving Donor Cell Engraftment
研究概览
简要总结
We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. However, we have found in past studies that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we plan to use a different combination of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors. The purpose of this research is to find a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality.
详细描述
This transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, Campath levels just prior to the administration of the graft, and establishment of mesenchymal stem cell lines. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.
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 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients eligible for transplantation under this protocol will be <45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.
- •Bones that are uniformly markedly dense based on skeletal survey
- •No history that would suggest autosomal dominant inheritance
- •Evidence of hematologic changes that are attributed to the underlying disease, including the need for ongoing transfusions, OR
- •the presence of progressive anemia or thrombocytopenia, OR a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR
- •persistence of serious infectious complications that are thought to be due to the abnormal architecture of the bone that are resistant to surgical and medical interventions.
排除标准
- •Patients >45 years of age
- •Evidence of hepatic failure
- •pulmonary dysfunction sufficient to substantially increase the risk of transplant
- •Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
- •Cardiac compromise sufficient to substantially increase the risk of transplantation
- •Severe, stable neurologic impairment.
- •Human immunodeficiency virus (HIV) positivity.
- •Pregnant or lactating females
研究组 & 干预措施
Intent-To-Treat
Patients enrolled and received study treatment.
干预措施: Stem Cell or Umbilical Cord Blood Transplantation (Procedure)
Intent-To-Treat
Patients enrolled and received study treatment.
干预措施: Campath, Busulfan, Clofarabine (Drug)
Intent-To-Treat
Patients enrolled and received study treatment.
干预措施: Total Lymphoid Irradiation (Procedure)
结局指标
主要结局
Number of Patients Achieving Donor Cell Engraftment
时间窗: Day 100
Number of patients with persistent presence of donor-derived cells at Day 100
次要结局
- Number of Patients With Transplant Related Death(Day 100)
- Number of Patients With Transplant Related Toxicity(Day 100)
- Differential Imaging and Biologic Evaluations(Day 100, 6 months, 1, 2 and 5 years)