Mesenchymal Stromal Cells Delivery Through Cardiopulmonary Bypass in Pediatric Cardiac Surgery
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Number of subjects who experience serious adverse events, adverse events, and/or early treatment discontinuations.
研究概览
简要总结
The proposed study will be a prospective, open-label, single-center, safety and feasibility phase 1 trial of allogeneic bone marrow-derived mesenchymal stromal cell (BM-MSC) delivery though cardiopulmonary bypass (CPB) using a homogeneous population of infants with congenital heart disease (CHD) who will be undergoing a two-ventricle repair within the first six months of life
详细描述
This study is a prospective, open-label, single-center, safety and feasibility phase 1 trial of allogeneic bone marrow-derived mesenchymal stromal cell (BM-MSC) delivery though cardiopulmonary bypass (CPB) using a homogeneous population of infants with congenital heart disease (CHD) who will be undergoing a two-ventricle repair within the first six months of life. The dose-escalation methods with a modified continual reassessment at the five dose levels (1x10^6, 10x10^6, 20x10^6, 40x10^6, 80x10^6, cells/kg) will be performed to determine safety and feasibility of allogeneic BM-MSC infusion during pediatric cardiac surgery and the maximum tolerated dose in infants with CHD. In addition to the primary objective of assessing the safety and feasibility of BM-MSC delivery through CPB, our secondary objectives are designed to develop biological signature measures and clinical outcome measures feasible for use in larger efficacy and effectiveness trials with a particular focus on neurodevelopmental outcome and early postoperative course after BM-MSC treatment. We will determine actual magnitude of differences in neuroimaging and neurodevelopmental variables and postoperative inflammatory and pathophysiological variables after BM-MSC delivery in infants with CHD. Enrollment, follow-up, and analysis are planned to occur over 36 months for the treatment and initial follow-up portions of the study. Long-term follow-up until 18 months of age will be subsequently reported.
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 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Neonatal and young infantile patients who are ≤ 6 months of age
- •Scheduled to undergo reparative two-ventricle repair for congenital heart defects without aortic arch reconstruction, including the following:
- •a. D-Transposition of the Great Arteries (d-TGA) Group: i. d-TGA with intact ventricular septum (d-TGA, IVS) ii. d-TGA with ventricular septal defect (d-TGA, VSD) b. Ventricular Septal Defect (VSD) Group: i. VSD without aortic arch obstruction (AAO) ii. Complete common atrioventricular canal defect (CAVC) c. Tetralogy of Fallot (TOF) Group: i. Tetralogy of Fallot (TOF) ii. Tetralogy of Fallot with Pulmonary Atresia (TOF,PA) iii. Truncus arteriosus (TA) iv. Double outlet right ventricle (DORV)
- •Scheduled surgery at or before three months of age.
- •Parent/guardian capable of providing informed consent.
排除标准
- •Birth weight less than 2.0 kg
- •Recognizable phenotypic syndrome
- •Associated extracardiac anomalies of greater than minor severity
- •Previous cardiac surgery
- •Associated cardiovascular anomalies requiring aortic arch reconstruction and/or additional open cardiac surgical procedures in infancy
- •Prior severe hypoxic event
- •Significant screening test values that place subjects at increased risk of complications from participation in the study
研究组 & 干预措施
Bone marrow-derived mesenchymal stromal cell (BM-MSC)
The dose-escalation methods with a modified continual reassessment at the five dose levels (1x10^6, 10x10^6, 20x10^6, 40x10^6, 80x10^6 cells/kg) will be performed to determine safety and feasibility of allogeneic BM-MSC infusion during pediatric cardiac surgery and the maximum tolerated dose in infants with CHD.
干预措施: BM-MSC (Biological)
结局指标
主要结局
Number of subjects who experience serious adverse events, adverse events, and/or early treatment discontinuations.
时间窗: 45 days following the MSC administration
Dose Limiting Toxicity is attributable to the MSC administration.
次要结局
- Actual magnitude of differences in neuroimaging and neurodevelopmental variables will be measured after MSC delivery.(18 months)
研究者
Catherine Bollard
Director, Center for Cancer and Immunology/ Center for Emerging Technologies in Immune Cell Therapies (CETI)
Children's National Research Institute