Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Repair of Hypoplastic Left Heart Syndrome

Study Overview
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Brief Summary
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Researchers want to better understand what happens to the heart when the stem cells are injected directly into the muscle of the right side of the heart during the Stage II palliative surgery for single ventricle patients with hypoplastic left heart syndrome (HLHS) or HLHS variant. Researchers want to see if there are changes in the heart's structure/function following this stem cell-based therapy and compared to children that have not had cell-based therapy.

Detailed Description
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This is a Phase IIb trial to determine if the delivery of the autologous UCB-MNC product into the myocardium of the right ventricle of the heart at the time of Stage II surgical repair will provide an improvement in cardiac function, reaching growth and developmental milestones, and quality of life, while also providing a reduction in the cumulative days of hospitalization following Stage II surgical repair. Long-term improvement in cardiac function, reaching growth and developmental milestones, reaching Stage III surgical repair pre-op work-up, prolonging time to cardiac transplantation or death, and improving quality of life will also be determined.

Official Title
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Phase IIb Study of Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Stage II Surgical Repair of Right Ventricular Dependent Variants of Hypoplastic Left Heart Syndrome (AutoCell-S2)

Conditions
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Hypoplastic Left Heart Syndrome

Intervention / Treatment
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* Biological: Autologous (self) mononuclear cells derived from umbilical cord blood
* Procedure: Stage II Surgical repair


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HLHS or HLHS variant with single right ventricular dependent CHD having undergone Stage I surgical repair and undergoing Stage II surgical repair. Less than 13 months of age at time of Stage II surgical repair Previous participation in the UCB collection protocol with autologous UCB-MNC product that is acceptable for use (treatment arm only) Exclusion Criteria: History of DMSO reaction (treatment arm only). Parent(s) and/or legal guardian(s) unwilling to have their child participate or unwilling to follow the study procedures. Severe chronic diseases at the discretion of the treating physician. Extensive extra-cardiac syndromic features. Known history of cancer. Any of the following complications of his/her congenital heart disease: Any condition requiring urgent, or unplanned interventional procedure within 15 days prior to Stage II surgical repair, unless complete and full cardiac recovery is documented by site investigator Severe pulmonary hypertension (reported in the medical record as >70% systemic pressure) Other clinical concerns as documented by a site investigator that would predict (more likely to happen than not to happen) a risk of severe complications or very poor outcome, not directly related to the stem cell product or its injection procedure, during or after Stage II surgical repair.

Ages Eligible for Study
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Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Autologous (self) mononuclear cells derived from umbilical cord blood and that meet all release criteria are injected into the surface of the right heart muscle to achieve the target dose of 1-3 million cells per kilogram body weight . This is a one time treatment at the time of Stage II Glenn surgery . | Biological: Autologous (self) mononuclear cells derived from umbilical cord blood<br>* The investigational product will be delivered into the right myocardium via sub-epicardial injections of 0.1 mL per kg body weight to achieve the target dose of 1-3 million TNC per kg body weight.at the time of Stage II surgical repair.<br>Procedure: Stage II Surgical repair<br>* This operation usually is performed about six months after Stage I surgery to divert half of the blood to the lungs when circulation through the lungs no longer needs as much pressure from the ventricle. The shunt to the pulmonary arteries is disconnected and the right pulmonary artery is connected directly to the superior vena cava, the vein that brings deoxygenated blood from the upper part of the body to the heart. This sends half of the deoxygenated blood directly to the lungs without going through the ventricle.<br>|
| Active Comparator: Control<br>Clinical data will be collected before, during and after the Stage II surgical standard of care procedure. Requires additional imaging studies at 3 months that are not standard of care in addition to some blood tests that would be beyond standard of care. Information will be collected to document the clinical outcomes and will be compared with the information from the group receiving the investigational treatment used in this study. | Procedure: Stage II Surgical repair<br>* This operation usually is performed about six months after Stage I surgery to divert half of the blood to the lungs when circulation through the lungs no longer needs as much pressure from the ventricle. The shunt to the pulmonary arteries is disconnected and the right pulmonary artery is connected directly to the superior vena cava, the vein that brings deoxygenated blood from the upper part of the body to the heart. This sends half of the deoxygenated blood directly to the lungs without going through the ventricle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Right Ventricular Cardiac Function measured by apical fractional area change (FAC) | Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent. | baseline, 3 months post-Stage II surgery | 
| Change in Right Ventricular Cardiac Function measured by circumferential strain. | Right ventricular cardiac function as measured by echocardiogram that includes studies for circumferential strain. Measured by percent. | baseline, 3 months post-Stage II surgery | 
| Change in Right Ventricular Cardiac Function measured by longitudinal strain. | Right ventricular cardiac function as measured by echocardiogram that includes studies for longitudinal strain. Measured by percent. | baseline, 3 months post-Stage II surgery | 
| Change in Right Ventricular Ejection Fraction | Right ventricular ejection fraction as measured by echocardiogram. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent. | baseline, 12 months post-Stage II surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ejection fraction | Ejection fraction as measured by echocardiogram. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent. | baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks) | 
| Cumulative days of hospitalization | Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair. | 1, 3-months post Stage II surgery | 
| Change in weight | Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used. | 3-months post Stage II surgery | 
| Change in heart rate | Heart rate as measured at home by subject's caregiver as standard of care per subject's provider. Caregivers will be instructed by the site staff on the best way to perform. | 3-months post Stage II surgery | 
| Change in oxygen saturation | Oxygen saturation as measured at home by subject's caregiver using the pulse oximetry device provided as standard of care by subject's provider. Caregivers will be instructed by the site to use the same pulse oximetry device for every home measurement of oxygen saturation. | 3-months post Stage II surgery | 
| Change in weight | Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used. | baseline, every 6 months post-Stage II surgery | 
| Change in heart failure medication | Changes in heart failure medications will be recorded by caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent. | baseline, every 6 months post-Stage II surgery | 
| Change in arrhythmia medication | Changes in arrhythmia medication will be recorded by subject's caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent. | baseline, every 6 months post-Stage II surgery | 
| Stage III surgical repair | The number of research subjects eligible for Stage III surgical repair | Stage III surgery pre-op, approx. 4 years | 
| Total time until listed for cardiac transplantation | The number of days between Stage II surgery and listed on cardiac transplantation list. | up to Stage III surgery pre-op, approx. 4 years | 
| Change in right ventricular function | Right ventricular ejection fraction as measured by echocardiogram, and cardiac catheterization. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent. | baseline, Stage III surgery pre-op | 
| Total time until death | The number of days between Stage II surgery and death occurrence | approx 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cells, HLHS, Hypoplastic Left Heart Syndrome, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord blood, Regenerative therapy, Stage II Glenn, Glenn Surgery, single ventricle