Clinical trial NCT01883076: Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome
Official title: Phase I Safety Study of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Stage II Palliation of Hypoplastic Left Heart Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypoplastic Left Heart Syndrome
Keywords: Hypoplastic Left Heart Syndrome
HLHS
Congenital Heart Disease
Umbilical cord blood
UCB
Cord blood
Stem cells
Regenerative therapy
Stage II Glenn
Glenn Surgery
Lead sponsor: ReGen Theranostics, Inc.
Sponsor class: OTHER
Collaborators: name: University of Oklahoma
name: Children's Hospital of Philadelphia
name: Children's Hospitals and Clinics of Minnesota
name: Children's Hospital Los Angeles
name: Children's Hospital Colorado
name: Mayo Clinic
First posted: 2013-06-21
Enrollment: 30
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase I study to determine the safety and feasibility of injections of autologous umbilical cord blood (UCB) cells into the right ventricle of Hypoplastic Left Heart Syndrome (HLHS) children undergoing a scheduled Glenn surgical procedure.

The investigators are doing this research study to find out if autologous stem cells from the individual's own umbilical cord blood can be used to strengthen the muscle of the right side of their heart. This will help determine the safety and feasibility of using cell-based regenerative therapy as an additional treatment for the management of HLHS.

Detailed description: This study is a Phase I trial to determine the safety of autologous mononuclear cells (MNC) derived from umbilical cord blood for intramyocardial delivery into the right ventricle during a planned and non-emergent Stage II surgical palliation in subjects with HLHS. This is the first critical step towards applying autologous MNC therapy as an add-on regenerative intervention for congenital heart disease management. The choice of HLHS as the target disease for regenerative therapies in congenital heart disease management is multi-factorial and includes the following considerations: 1) Severity of of this incurable disease, 2) palliative nature and burden of long-term outcomes with a single right ventricular system, 3) three stages of planned surgical procedures that provide time points to adjunctively intervene, and 4) prenatal diagnosis enabling planned collection of UCB. An emerging goal for cardiac regeneration includes the application of cell-based technology to congenital heart disease, which is a favorable substrate due to the lack of fibrotic scaring, and the presence of a microenvironment that is expected to support ongoing cardiac proliferation and growth for functional remuscularization. This Phase I safety study will determine the feasibility of collection, processing, and delivery of autologous cells as used in adult cardiac regenerative protocols in the setting of HLHS surgical management.

Eligibility criteria: Inclusion Criteria

1. Individuals with autologous cord blood product that met all cell release criteria (listed on the certificate of analysis from Mayo Clinic Human Cell Therapy Lab) as follows:

   1. No aerobic or anaerobic bacterial growth after 14 days
   2. Greater than 70% cell viability pre-freeze
   3. Total Nucleated Cells (TNC) concentration of 30-42 x 106 cells/mL (pre-freeze)
   4. Minimum of one (1) vial of cells
   5. Mononuclear cell percentage of greater than 50%
   6. Endotoxin result of less than 16 Endotoxin Units (EU)/mL.
2. Mother's serology test results are negative for HIV, Hepatitis B, and Hepatitis C.
3. Individuals with HLHS having undergone Stage I surgical palliation and undergoing planned Stage II palliative Glenn surgery.
4. Ages up to 18 months are eligible if written informed consent can be obtained from both parents (unless one parent is not reasonably available) and/or legal guardians.

Exclusion Criteria

1. Child who's UCB does not meet the specified cell release criteria in Inclusion Criterion #1.
2. History of dimethyl sulfoxide (DMSO) reaction for either the child or mother.
3. Parent(s)/child unwilling to participate.
4. Child with severe chronic diseases, extensive extra-cardiac syndromic features, or history of cancer.
5. Child not completing all pre-procedure work-up within 10 days of the Stage II Glenn surgery as listed in section 6 of this protocol AND lack of pre-procedure work-up documented as a safety concern by a site investigator.
6. Child who's cells have been compromised after meeting cell release criteria (as defined in Inclusion Criterion #1).
7. Child with the following complications of their congenital heart disease:

   1. Any condition requiring urgent, or unplanned procedure within 15 days prior to Stage II surgical repair
   2. Severe pulmonary hypertension (reported in the medical record as \>70% systemic pressure)
   3. 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 during or after Stage II surgical repair.

Primary outcomes:
measure: Incidence of all-cause mortality
timeFrame: Within 2 years following cell therapy treatment
measure: Incidence of new and worsening adverse cardiac events
timeFrame: Within 2 years following cell therapy treatment
measure: Percentage of subjects whose cells meet all cell release criteria
timeFrame: Up to 2 years
measure: Percentage of subjects enrolled who undergo cell therapy treatment
timeFrame: Up to 2 years
Secondary outcomes:
measure: Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiography
timeFrame: baseline, 1 month
measure: Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiography
timeFrame: baseline, 3 months
measure: Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiography
timeFrame: baseline, 6 months
measure: Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiography
timeFrame: baseline, 1 month
measure: Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiography
timeFrame: baseline, 3 months
measure: Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiography
timeFrame: baseline, 6 months
measure: Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiography
timeFrame: baseline, 1 month
measure: Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiography
timeFrame: baseline, 3 months
measure: Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiography
timeFrame: baseline, 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Minneapolis
country: United States
facility: Children's Hospital of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Oklahoma City
country: United States
facility: Oklahoma University Children's Hospital
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Mayo Clinic
name: Timothy J Nelson, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: Mayo Clinic
name: Muhammad Y Qureshi, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Oklahoma University Children's Hospital
name: Harold M Burkhart, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Joseph W Rossano, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Minnesota
name: David M Overman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Los Angeles
name: Ram Kumar Subramanyan, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Colorado
name: James Jaggers, M.D.
role: PRINCIPAL_INVESTIGATOR
References: