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Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome

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ClinicalTrials.gov Identifier: NCT01883076
Recruitment Status : Recruiting
First Posted : June 21, 2013
Last Update Posted : March 12, 2019
Sponsor:
Collaborators:
University of Oklahoma
Children's Hospital of Philadelphia
Children's Hospitals and Clinics of Minnesota
Children's Hospital Los Angeles
Children's Hospital Colorado
Information provided by (Responsible Party):
Timothy J. Nelson, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE June 11, 2013
First Posted Date  ICMJE June 21, 2013
Last Update Posted Date March 12, 2019
Actual Study Start Date  ICMJE May 15, 2013
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2016)
  • Incidence of all-cause mortality [ Time Frame: Within 2 years following cell therapy treatment ]
  • Incidence of new and worsening adverse cardiac events [ Time Frame: Within 2 years following cell therapy treatment ]
    The adverse cardiac events would include sustained/symptomatic ventricular arrhythmias, heart failure, myocardial infarction, cardiac infections, and unexpected cardiovascular surgery.
  • Percentage of subjects whose cells meet all cell release criteria [ Time Frame: Up to 2 years ]
  • Percentage of subjects enrolled who undergo cell therapy treatment [ Time Frame: Up to 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2013)
  • Number of patients completing consent, collection of umbilical cord blood, and intramyocardial delivery of autologous stem cells [ Time Frame: 1 week post Glenn procedure ]
    The percentage of patients consented for the study that have successfully undergone umbilical cord blood collection, completed GMP-processing to meet release criteria, and achieved uncomplicated intramyocardial cell delivery will determine the feasibility of this approach.
  • Number of patients with cardiac-related adverse events [ Time Frame: up to 6 months follow-up post Glenn procedure ]
    Upon intramyocardial cell delivery at the time of planned Glenn procedure, signs of cardiac toxicity will be measured according to worsening of ejection fraction by more than 10%, any new cardiac arrhythmias that could be attributed to stem cell therapy based on follow-up electrocardiograms and 24-hr Holter monitoring, and abnormal routine blood chemistry to monitor for evidence of organ failure.
Change History Complete list of historical versions of study NCT01883076 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2016)
  • Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
  • Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
  • Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]
  • Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
  • Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
  • Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]
  • Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
  • Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
  • Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2013)
Change in right ventricular ejection fraction according to cardiac imaging with echocardiography [ Time Frame: 6 months follow-up post Glenn procedure ]
The secondary analysis is focused on the potential benefit of intramyocardial delivery of the manufactured cell-based product in pediatric hearts at the time of planned surgical palliation for HLHS. The change from baseline to 1, 3, and 6-month follow-up in right ventricular ejection fraction is the primary variable along with secondary variables of change in right ventricle TAPSE and fractional area change.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome
Official Title  ICMJE Phase I Safety Study of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Stage II Palliation of Hypoplastic Left Heart Syndrome
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hypoplastic Left Heart Syndrome
Intervention  ICMJE Biological: autologous cell-based delivery
autologous cells (derived from "self")
Other Name: umbilical cord blood derived mononuclear cells
Study Arms  ICMJE Experimental: autologous cell-based delivery
autologous cell-based delivery a target dose of 3 million cells / kg of body weight will be delivered into the right heart muscle at the time of surgery. Cells are derived from autologous (self) umbilical cord blood.
Intervention: Biological: autologous cell-based delivery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 8, 2019)
30
Original Estimated Enrollment  ICMJE
 (submitted: June 20, 2013)
10
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Karen S Miller (507) 266-5510 miller.karen1@mayo.edu
Contact: Karen M Cavanaugh (507) 538-8425 cavanaugh.karen@mayo.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01883076
Other Study ID Numbers  ICMJE 12-008521
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Timothy J. Nelson, Mayo Clinic
Study Sponsor  ICMJE Timothy J. Nelson
Collaborators  ICMJE
  • University of Oklahoma
  • Children's Hospital of Philadelphia
  • Children's Hospitals and Clinics of Minnesota
  • Children's Hospital Los Angeles
  • Children's Hospital Colorado
Investigators  ICMJE
Study Director: Timothy J Nelson, M.D., Ph.D. Mayo Clinic
Principal Investigator: Muhammad Y Qureshi, MBBS Mayo Clinic
Principal Investigator: Harold M Burkhart, M.D. Oklahoma University Children's Hospital
Principal Investigator: Joseph W Rossano, M.D. Children's Hospital of Philadelphia
Principal Investigator: David M Overman, M.D. Children's Hospital of Minnesota
Principal Investigator: Ram Kumar Subramanyan, M.D., Ph.D. Children's Hospital Los Angeles
Principal Investigator: James Jaggers, M.D. Children's Hospital Colorado
PRS Account Mayo Clinic
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP