Safety and Feasibility Study of Umbilical Cord Blood Cells for Infants With Hypoplastic Left Heart Syndrome

• ClinicalTrials.gov Identifier: NCT01445041
• Recruitment Status: Terminated
• First Posted: October 3, 2011
• Last Update Posted: January 21, 2020
• Sponsor: Michael Cotten
• Information provided by (Responsible Party): Michael Cotten, Duke University

Tracking Information

• First Submitted Date: September 15, 2011
• First Posted Date: October 3, 2011
• Last Update Posted Date: January 21, 2020
• Actual Study Start Date: September 1, 2011
• Actual Primary Completion Date: April 15, 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 29, 2011): Adverse event rates occurring in the pilot study population. The investigators will compare infusion outcomes of infants infused with frozen cells and infants infused with non-frozen cells. [ Time Frame: During Infusions (First 2 months of life) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 15, 2013)

Feasibility and preliminary efficacy [ Time Frame: 1 year ]

Feasibility: volume of cord blood, cell viability, time to prepare/infuse fresh cells and frozen-thawed cells. Preliminary efficacy: neurodevelopmental outcomes at 9 - 12 months, cardiac function as assessed clinically.

Original Secondary Outcome Measures (submitted: September 29, 2011)

Feasibility and preliminary efficacy [ Time Frame: 1 year ]

Feasibility: volume of cord blood, cell viablity, time to prepare/infuse fresh cells and frozen-thawed cells. Preliminary efficacy: neurodevelopmental outcomes at 9 - 12 months, cardiac function as assessed clinically.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Feasibility Study of Umbilical Cord Blood Cells for Infants With Hypoplastic Left Heart Syndrome
• Official Title: Autologous Cord Blood Cells for Patients With HLHS: Phase I Study of Feasibility and Safety

Brief Summary

Further study details as provided by Duke University:

Purpose: To evaluate the feasibility and safety of collecting and infusing autologous umbilical cord blood (UCB) in newborn infants with hypoplastic left heart syndrome (HLHS).

Study Rationale and Hypotheses: The major goal of this study is to determine whether infusion of autologous UCB cells in neonates with hypoplastic left heart syndrome is feasible and safe. The rationale for the study and for the potential benefit of UCB is based upon the following hypotheses:

1. Infants with HLHS have significant neural injury evidenced from both prenatal and early antenatal brain MRI findings and infusion of UCB cells may lessen neural injury. Although the exact mechanism is unknown, UCB cell infusion may ameliorate neural injury via paracrine and anti-inflammatory effects that enhance post injury repair and may promote endogenous functional compensation of other cortical areas resulting in significant clinical improvements.
2. UCB cells may also enhance cardiac function, minimize scar formation, and reverse detrimental remodeling after cardiac injury.

• Detailed Description: The purpose of this pilot study is to evaluate the safety and feasibility of infusions of autologous (the patient's own)umbilical cord blood cells in neonates with hypoplastic left heart syndrome. This is a prospective, randomized Phase I trial designed to assess the safety and feasibility of autologous UCB reinfusion in neonates with Hypoplastic Left Heart Syndrome (HLHS). Neonates who are identified prenatally as having a cardiac lesion consistent with HLHS will be referred to Duke Cardiology for further evaluation. If they meet inclusion criteria, UCB will be collected at the time of delivery and processed (red blood cell- and volume-reduced) for reinfusion. All enrolled infants will receive a dose of fresh UCB cells pre-operatively and ½ of the enrolled infants will be randomly selected to receive a second dose of frozen and thawed UCB cells after stage 1 palliation (5-35 days post-operatively) and a third dose of frozen and thawed UCB cells 2 to 4 weeks after the 2nd infusion. Neurodevelopmental outcome measures will be assessed at 1 month after discharge, at 4-6 months old and 12 months. The results of MRI's and echocardiograms that are obtained per clinical routine will be analyzed and described in study reports.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hypoplastic Left Heart Syndrome

Intervention

• Biological: Autologous Umbilical Cord Blood
  Infants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 1 infusion of their own volume reduced cord blood cells. The dose for each infusion is 5x10e7 cells/kg.
• Biological: Autologous Umbilical Cord Blood
  Infants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 3 infusions of their own volume reduced cord blood cells. The first infusion will be a fresh, volume-reduced infusion and the subsequent infusions will be thawed and washed infusions. The dose for each infusion is 5x10e7 cells/kg.

Study Arms

• Experimental: Single infusion of UCB
  (autologous red blood cell and volume reduced cord blood cells)
  Intervention: Biological: Autologous Umbilical Cord Blood
• Experimental: Three infusions of UCB
  (autologous red blood cell and volume reduced cord blood cells)
  Intervention: Biological: Autologous Umbilical Cord Blood

Publications *

• Martin PL, Carter SL, Kernan NA, Sahdev I, Wall D, Pietryga D, Wagner JE, Kurtzberg J. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. 2006 Feb;12(2):184-94.
• Kurtzberg J, Lyerly AD, Sugarman J. Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood. J Clin Invest. 2005 Oct;115(10):2592-7. Review.
• Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81.
• Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit W, Kurtzberg J. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med. 2004 May 6;350(19):1960-9.
• McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM. Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience. Radiology. 2005 Jul;236(1):221-30.
• Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, Clancy RR, Montenegro LM, Spray TL, Chiavacci RM, Wernovsky G, Kurth CD. An MRI study of neurological injury before and after congenital heart surgery. Circulation. 2002 Sep 24;106(12 Suppl 1):I109-14.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 16, 2020): 7
• Original Estimated Enrollment (submitted: September 29, 2011): 20
• Actual Study Completion Date: April 15, 2016
• Actual Primary Completion Date: April 15, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Infants > 35 weeks gestational age.
• Diagnosis: Hypoplastic Left Heart Syndrome.
• Autologous umbilical cord blood available with a minimum total nucleated cell dose of 1 x 10e7 cells/kg.
• Parental Consent.

Exclusion Criteria:

• Chromosomal anomalies identified before the time of infusion.
• Chromosomal anomalies or congenital anomalies that would prohibit clinicians from initiating surgical repair of the congenital heart defect.
• Infant is determined by clinical staff to be non-viable and will not receive aggressive care. (No member on the study team will be involved in determining the viability of the neonate.)

• Autologous umbilical cord blood unit has any of the following:

  • Total nuclear cell count < 1 x 10e7.
  • Positive maternal infectious serology (except CMV).
  • Evidence of infectious contamination of the cord blood unit.
  • Evidence of genetic disease.
• Unable to obtain parental consent.
• Mother < 18 years old.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 2 Days (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01445041
• Other Study ID Numbers: Pro00024650
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Michael Cotten, Duke University
• Original Responsible Party: Duke University
• Current Study Sponsor: Michael Cotten
• Original Study Sponsor: Duke University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Charles M Cotten, MD MHS; Duke University

• PRS Account: Duke University
• Verification Date: January 2020