Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Patients Who Achieved Donor Cell Engraftment
研究概览
简要总结
The purpose of this research is to explore what we believe may be 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. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design 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.
详细描述
This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 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, and evaluation of blood parameters and genes that may be important in the disease process. 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
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 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 < or = 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 significantly 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
cord blood transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42.
干预措施: umbilical cord blood transplantation (Procedure)
marrow graft transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.
干预措施: Campath-1H (Drug)
marrow graft transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.
干预措施: Total Lymphoid Irradiation (Radiation)
marrow graft transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.
干预措施: Busulfan (Drug)
marrow graft transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.
干预措施: Fludarabine monophosphate (Drug)
marrow graft transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.
干预措施: marrow graft transplantation (Procedure)
cord blood transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42.
干预措施: Campath-1H (Drug)
cord blood transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42.
干预措施: Cyclophosphamide (Drug)
cord blood transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42.
干预措施: Busulfan (Drug)
结局指标
主要结局
Number of Patients Who Achieved Donor Cell Engraftment
时间窗: Day 100
次要结局
- Incidence of Grade II - IV Acute Graft-versus-host Disease(by Day 100 after transplant)
- Transplant Related Mortality at 100 Days(day 100)
- Transplant Related Toxicity(Day 100 post transplant)