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

The primary purpose of this protocol is to enable access to autologous (a person's own)
or allogeneic (someone else's) umbilical cord blood infusion for children with various
brain disorders. Children with cerebral palsy, hydrocephalus, hypoxic brain injury,
stroke, apraxia, and other brain injuries may be eligible if they do not qualify for or
are unable to participate in another active clinical trial at Duke. For the purpose of
this protocol the term children refers to patients less than 26 years of age. Cord blood
infusions are still being studied to determine if they are effective in helping to treat
certain types of brain injuries.

If being seen at Duke, 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". 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 and unrelated
donor cord blood infusions, the intended recipient and their sibling must be at least a
half HLA match, and in the case of an unrelated donor, a 4/6 match.

If eligible, the participant will come to the hospital 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. On the day of infusion, CB cells will be thawed and transported to the Pediatric
clinic for infusion to the participant under the supervision of the treatment team and/or
clinic staff. A peripheral IV will be placed. Some children may require numbing cream
and/or intranasal or oral versed prior to IV placement. Prior to the infusion of cells,
premedications (Benadryl, Solumedrol) will be administered. The CB will be infused over
approximately 5-15 minutes using standard practices. The participant will receive
maintenance IV fluids and be observed in the clinic for a minimum of thirty minutes after
the infusion. Participants will be discharged from clinic after at least thirty minutes,
providing all vital signs are at their baseline and they are awake, taking oral fluids,
and asymptomatic with no evidence of toxicity.

If a participant has evidence of illness on the day of planned infusion, including but
not limited to fever, vomiting, diarrhea, or respiratory distress, the infusion will be
postponed.

In the event that a participant develops signs or symptoms of anaphylaxis including rash,
difficulty breathing, cough, wheezing, or vomiting during their CB infusion, the infusion
will be terminated or slowed and appropriate medical therapy initiated.

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.

Multiple CB infusions may be administered from the same or two unique CB donors, but
subsequent infusions will depend upon the quality and availability of an autologous or
sibling cord blood unit and the need to limit exposure of the participant to new HLA
antigens.

Required Evaluations:

1. Screening:

1. blood counts, blood chemistries, participant HLA typing, blood type (for
females receiving allogeneic CB units)

2. confirmatory HLA typing of the cord blood unit

2. Baseline Visit:

1. History and Physical Exam

2. Pregnancy test (blood test for menstruating females)

3. blood counts, blood chemistries, if not performed during screening or within 12
months prior to the baseline visit

4. infectious disease testing, blood type, test for antibodies against donor blood
type (for those receiving allogenic cord blood)

3. Safety Assessments

1. phone call the day after the infusion

2. email safety survey at 1 and 2 years after the infusion