Expanded Access Protocol: Umbilical Cord Blood Infusions for Children With Brain Injuries

Study Overview
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Brief Summary
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The purpose of this protocol is to enable access to intravenous infusions of banked autologous (a person's own) or sibling umbilical cord blood (CB) for children with various brain disorders. This is an expanded access protocol intended for patients who are unable to participate in a clinical trial involving their own or their sibling's cord blood. Children with cerebral palsy, congenital hydrocephalus, apraxia, stroke, hypoxic brain injury and related conditions will be eligible if they have normal immune function and do not qualify for, have previously participated in, or are unable to participate in an active cell therapy clinical trial at Duke Medicine. For the purpose of this protocol the term children refers to patients less than 26 years of age. The cord blood is thawed and then administered as an intravenous infusion. Recipients do not receive chemotherapy or immunosuppression. The mechanism of action is through paracrine signaling of cord blood monocytes inducing endogenous cells to repair existing damage.

Detailed Description
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This protocol is designed to enable access to intravenous infusions of banked autologous (a person's own) or sibling umbilical cord blood (CB) for children with various brain disorders. Children with cerebral palsy, congenital hydrocephalus, apraxia, stroke, hypoxic brain injury and related conditions will be eligible if they have normal immune function and do not qualify for, have previously participated in, or are unable to participate in an active cell therapy clinical trial at Duke Medicine. For the purpose of this protocol the term children refers to patients less than 26 years of age. Cord blood is administered as a cellular infusion without prior treatment with chemotherapy or immunosuppression. The use of CB in this fashion is based on safety and efficacy data from prior and ongoing clinical trials at Duke University Medical Center in over 700 patients over the past decade. The mechanism of action is through paracrine signaling of cord blood monocytes inducing endogenous cells to repair existing damage. Of note, CB is thawed, washed and infused through a peripheral IV without prior or post-infusion immunosuppression. Initially, the participant will be enrolled on the screening protocol, A Research Database and Screening Protocol for Children with Brain Injuries Potentially Undergoing Cellular Therapy or Other Clinical Trials, Pro00063563. Information about the participant's health and eligibility will be obtained under this protocol and may include records such as diagnostic information, genetic testing, videos, pictures of the child, and a cord blood report. The study team will review these records to determine if the child and the cord blood unit are eligible. For all cord blood infusions, the unit must meet certain cell count, sterility, and viability criteria. For sibling cord blood infusions, the intended recipient and their sibling must be at least a half HLA match. If eligible, the participant will come to Duke with a parent or legal guardian for clinical evaluations and infusion of the umbilical cord blood unit. Typically, medical evaluations are done on day one of the visit and the infusion is given on day two. Parents will be required to participate in remote follow-up phone calls and be willing to complete questionnaires for safety follow ups. Safety questionnaires will be sent by email at one and two years after the infusion.

Official Title
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Expanded Access Protocol: Umbilical Cord Blood Infusions for Children With Brain Injuries

Conditions
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Cerebral Palsy, Hydrocephalus, Apraxia of Speech, Hypoxia Ischemia, Cerebral, Drowning; Anoxia

Intervention / Treatment
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* Biological: Cord Blood Infusion


Participation Criteria
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Eligibility Criteria
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Patients with documented cerebral palsy, hypoxic brain injury, stroke, hydrocephalus, apraxia or other brain injuries will be eligible. In addition, patients who have competed participation in a prior Duke cell therapy study (CP-AC, Duke ACT, CPSib, ACCeNT-CP, TACT, IMPACT) and who have an eligible/qualified autologous or sibling cord blood unit are eligible. To be eligible, patients must: Inclusion Criteria: Have a qualifying sibling or autologous cord blood unit Be < 26 years of age at the time of consent. Have given written informed consent according to FDA guidelines (or consent of parent/legal guardian as applicable). Have baseline blood counts and basic chemistries within normal for age. Have a normal absolute lymphocyte count (ALC) for age on baseline blood count and differential. Exclusion Criteria: Documented HIV or Hepatitis or other disease transmittable through the blood. A cord blood unit that fails to meet specifications Refusal of consent Uncontrolled seizure disorder Uncontrolled infection Diagnosed with a genetic or metabolic disorder related to the neurologic condition History of an immune deficiency History of treatment with chemo or immunosuppressive therapy History of previous allogeneic cell therapy outside of participation in a Duke clinical trial Need for mechanical ventilation or chronic O2 support Unstable airway Eligible for an active clinical trial of cellular therapy at Duke. If previously enrolled on another Duke cell therapy protocol the subject can still be considered for enrollment on this study after the follow-up period for the clinical trial is completed. Pregnant or breastfeeding Umbilical Cord Blood Criteria Patient enrollment is dependent on the availability of a banked unit of autologous or full or partially (at least half) matched allogeneic sibling CB that has been stored at a private or public bank and meets the following criteria: Precryopreservation: TNCC ≥2x107/kg Sterility cultures performed and negative Viability ≥70% At least haploidentical HLA match for sibling units Donor screening testing performed and negative CBU Test sample Segment or test vial available Identity confirmed via HLA typing of test sample and donor Viability testing recommended, but not required

Ages Eligible for Study
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Maximum Age: 26 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Cord Blood Infusion|IV infusion of umbilical cord infusion (sibling or autologous)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |