Congenital Heart Disease (CHD)
Conditions
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
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 (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.
Interventions
BIOLOGICALBM-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.
Sponsors
Catherine Bollard
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
Inclusion criteria
* 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.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRichard Jonas, MD
CNMC
Outcome results
None listed