Safety of Autologous Human Umbilical Cord Blood Treatment for Perinatal Arterial Ischemic Stroke

NCT02460484 | Suspended Phase 1 DMC

• 1 other identifier: 443002
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Autologous human umbilical cord blood (hUCB) stored at Cord Blood Registry will be given to children who have suffered from a Perinatal Arterial Ischemic Stroke. The aim is to determine if hUCB infusion is safe, if late functional outcome is improved, if hUCB treatment improves physiologic response in the child's SSEP \& EEG, and the effect of hUCB infusion in altering anatomic findings on MRI.

Conditions

Perinatal Arterial Ischemic Stroke

Outcome Measures

Primary Outcomes (4)

• Composite Outcome: Hemodynamic Safety

  Three primary and two secondary hemodynamic indices will be monitored as indices of hemodynamic stability throughout the infusion and post-infusion periods. Heart rate, blood pressure, and oxygen saturation will be recorded every 5 minutes during the infusion, every 30 minutes for 2 hours after infusion and then hourly for 6 hours. A consistent, non-isolated 20% decrease in any of these indices will be prompt additional maneuvers to restore MAP. Two secondary hemodynamic indices will be monitored as indices of hemodynamic stability: capillary refill and heart rate. Prolongation of capillary refill by 2 seconds from baseline and/or \>20% change in heart rate during the procedure will prompt an evaluation as to the etiology of the change in hemodynamic status. An adverse event will be defined as a sustained (\> 10 minutes) \>20% decrease in MAP. Transient decreases in MAP that respond to fluid infusion or inotropes will not be considered adverse events.

  1 year

• Composite Outcome: Pulmonary Safety

  A concern exists regarding the systemic infusion of leukocytes in a concentrated manner. Theoretically, activated monocytes could function to enhance PMN migration into the lung, as the lung is the primary "first pass" filter for intravenous infusion of any cellular product. PMN mediated organ injury typically occurs over a 6-24 hour time frame. Based on this, Chest radiographs will be performed and evaluated at Baseline and on Post-Infusion Day 1. Chest radiographs will be evaluated for systemic infusion of leukocytes in a concentrated manner. Additionally, blood-oxygen saturation will be monitored by finger oximeter. Moderate respiratory dysfunction within the first 48 hours post infusion will be considered an adverse event but will not warrant stopping the trial unless recommended by the DSMB. In the event of pulmonary dysfunction, standard supportive therapy will be given. Pulmonary symptoms/events corresponding to the CTCAE v3.0 Grade 3 will trigger the stopping rules.

  1 year

• Composite Outcome: Renal Safety

  To minimize the effect of DSMO, our hUCB product will be washed according to Standard Operating Procedures prior to infusion. Though unlikely, it is possible that some quantity of DMSO will remain which could cause toxicity. Renal function/events corresponding to the CTCAE v3.0 Grade 3 will trigger the stopping rules

  1 year

• Composite Outcome: Neurological Safety

  The patient's acute neurologic status will be monitored until discharged. Data recorded every 4 hours includes GCS, pupillary size/reactivity, motor/sensory evaluation of extremities, and seizure activity from infusion to discharge. Grade 3-5 CNS event as defined in the NCI CTCAE v3.0 occurring within 12 hours of cellular product infusion will trigger the stopping rules. Other changes temporally related to hUCB infusion (those events occurring within 12 hours of infusion) will be considered associated with the protocol and recorded as an adverse event.

  1 year

Secondary Outcomes (5)

• EEG

  1 year

• Fine and Gross Motor

  1 year

• Language

  1 year

• Speech

  1 year

• Bladder: Urodynamics

  1 year

Study Arms (1)

Cord Blood Infusion

EXPERIMENTAL

Autologous cord blood infusion

Biological: Autologous Cord Blood Infusion

Interventions

Autologous Cord Blood Infusion BIOLOGICAL

Intravenous infusion

Cord Blood Infusion

Eligibility Criteria

• Age: 6 Weeks - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Between 6 weeks and 6 years of age on the day of study cord blood infusion.
• MRI documented single arterial distribution infarction.
• Initial injury occurring in the prenatal or perinatal period
• Ability of child and caregiver to travel to Orlando, and stay for at least 4 days, and to return for all Follow-up visits (patient is responsible for cost of travel and lodging while in Orlando)

You may not qualify if:

• Inability to obtain all pertinent medical records, including pertinent physician notes, laboratory findings, and radiographic images, related to the original injury, hospitalization and rehabilitation - must be sent to FHFC research team 14 days prior to scheduled study cord blood treatment. Need brain MRI with flair sequence \<2 weeks old.
• Recent radiographic evidence (imaging performed within past 2 weeks) of extensive stroke as evidenced by \>100ml lesion
• Multifocal infarctions on screening MRI.
• Evidence of hypoxic-ischemic encephalopathy on screening MRI.
• Uncorrected coagulopathy during the baseline period defined as INR \> 1.4; PTT\> 35 sec; PLT \< 100,000
• Known history of:
• Recently diagnosed infection (within past 2 weeks) requiring treatment and/or medical intervention
• Renal disease or altered renal function as defined by serum creatinine \>1.5 mg/dL at admission
• Hepatic disease or altered liver function as defined by SGPT \> 150 U/L, and/or T. Bilirubin \>1.3 mg/dL at enrollment
• Malignancy
• Immunosuppression as defined by WBC \< 3 (10x3) at admission
• HIV
• Any evidence of active maternal infection during the pregnancy (Hepatitis A, Hepatitis B, Hepatitis C, HIV 1, HIV 2, Human T-lymphotropic Virus (HTLV) 1, HTLV 2
• Pneumonia, or chronic lung disease requiring oxygen
• Cord blood sample contamination

Sponsors & Collaborators

• James Baumgartner, MD: lead
• Cord Blood Registry, Inc.: collaborator

Study Sites (1)

Florida Hospital for Children

Orlando, Florida, 32803, United States

Location

Study Officials

• James Baumgartner, MD

  AdventHealth

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: April 23, 2015
• First Posted: June 2, 2015
• Study Start: April 1, 2015
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: March 18, 2022

Record last verified: 2022-03

Locations

US (1)