Clinical trial NCT02599207: Assessment of the Safety of Allogeneic Umbilical Cord Blood Infusions in Children With Cerebral Palsy
Official title: Assessment of the Safety of Allogeneic Umbilical Cord Blood Infusions in Children With Cerebral Palsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cerebral Palsy
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2015-11-06
Enrollment: 15
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a single site, phase I, prospective study of the safety of intravenous sibling cord blood infusion in 15 children ages 1-6 years with Cerebral Palsy (CP). All subjects will be treated with sibling cord blood cells. The first six will receive cord blood cells from an HLA-matched sibling. The following nine subjects will receive cord blood cells from an HLA-mismatched (≥3/6 match) or matched sibling. The duration of study participation will be six months from the time of the cord blood infusion.

Detailed description: This study is a phase I, prospective, open-label trial designed to assess the safety of a single allogeneic sibling cord blood infusion in young children with cerebral palsy. Children ages one to six years with uncomplicated cerebral palsy and an available HLA matched or haploidentical, qualified, sibling cord blood unit will be eligible to participate. All participants will receive a single intravenous infusion of allogeneic sibling cord blood. All participants will have an initial clinical evaluation to verify the diagnosis of cerebral palsy and determine eligibility. The main endpoint is safety, for which acute infusion reactions as well as incidence of infections and graft versus host disease will be assessed. Functional outcome measures, described below, will be assessed at baseline and six months post sibling cord blood infusion and described.

Eligibility criteria: Inclusion Criteria:

1. Age ≥12 months and ≤ 6 years at the time of CB infusion.
2. Diagnosis: Cerebral palsy with diplegia, hemiplegia, or quadriplegia.
3. Performance status:

   * Bilateral cerebral palsy (diplegia or quadraplegia):

   Gross Motor Function Classification Score levels II - IV, or Gross Motor Function Classification Score level I, age ≥ 2 years
   * Hemiplegia: Gross Motor Function Classification Score levels II - IV or minimal functional capabilities in the affected upper extremity. A subject classified as GMFCS level I with significant upper extremity impairment will be eligible if the affected upper extremity is used as an assist only.
4. Review of brain imaging (obtained as standard of care prior to study entry) does not suggest a genetic condition or brain malformation.
5. Suitably matched sibling donor CB unit (see section 6.2 for matching details) available at a private or public cord blood bank with a minimum total nucleated cell dose of ≥ 2.5 x 107 cells/kilogram.
6. Legal authorized representative consent.

Exclusion Criteria:

1. Available qualified autologous cord blood unit
2. Autism and autistic spectrum disorders without motor disability.
3. Hypsarrhythmia.
4. Intractable seizures causing epileptic encephalopathy.
5. Evidence of a progressive neurologic disease.
6. Has an active, uncontrolled systemic infection or documentation of HIV+ status.
7. Known genetic disease or phenotypic evidence of a genetic disease on physical exam.
8. Concurrent genetic or acquired disease or comorbidity(ies) that could require a future allogeneic stem cell transplant.
9. Requires ventilatory support, including home ventilator, CPAP, BiPAP, or supplemental oxygen.
10. Impaired renal or liver function as determined by serum creatinine \>1.5mg/dL and/or total bilirubin \>1.3mg/dL except in patients with known Gilbert's disease.
11. Possible immunosuppression, defined as WBC \<3,000 cells/mL or absolute lymphocyte count (ALC) below normal for age with abnormal T-cell subsets.
12. Patient's medical condition does not permit safe travel.
13. Previously received any form of cellular therapy.

Primary outcomes:
measure: Assessment for infusion reactions, infections, graft versus host disease or any other adverse events
timeFrame: 6 months
Secondary outcomes:
measure: Assessment for improvement in gross motor function
timeFrame: 6 months
measure: Assessment for improvement in fine motor function
timeFrame: 6 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Joanne Kurtzberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Jessica Sun, MD
role: PRINCIPAL_INVESTIGATOR
References: