Mesenchymal Stromal Cells for Infants With Congenital Heart Disease (MedCaP)
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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 (1x106, 10x106, 20x106, 40x106, 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Biological: BM-MSC
Allogeneic bone marrow-derived mesenchymal stromal cell (BM-MSC) delivery through 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.
|
Outcome Measures
Primary Outcome Measures
- Number of subjects who experience serious adverse events, adverse events, and/or early treatment discontinuations. [45 days following the MSC administration]
Dose Limiting Toxicity is attributable to the MSC administration.
Secondary Outcome Measures
- Actual magnitude of differences in neuroimaging and neurodevelopmental variables will be measured after MSC delivery. [18 months]
Secondary objective will be measured by using the Pediatric Cardiac Critical Care Consortium (PC4) registry system.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Neonatal and young infantile patients who are ≤ 3 months of age
-
Scheduled to undergo reparative two-ventricle repair for congenital heart defects without aortic arch reconstruction, including the following:
- 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)
- Ventricular Septal Defect (VSD) Group: i. VSD without aortic arch obstruction (AAO)
- 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.
Exclusion Criteria:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's National Health System | Washington | District of Columbia | United States | 20010 |
Sponsors and Collaborators
- Catherine Bollard
Investigators
- Principal Investigator: Richard Jonas, MD, CNMC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00011914