Assessment of the Safety of Allogeneic Umbilical Cord Blood Infusions in Children With Cerebral Palsy

• ClinicalTrials.gov Identifier: NCT02599207
• Recruitment Status: Completed
• First Posted: November 6, 2015
• Last Update Posted: December 4, 2019
• Sponsor: Joanne Kurtzberg, MD
• Information provided by (Responsible Party): Joanne Kurtzberg, MD, Duke University

Tracking Information

• First Submitted Date: November 2, 2015
• First Posted Date: November 6, 2015
• Last Update Posted Date: December 4, 2019
• Study Start Date: November 2015
• Actual Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 5, 2015)

Assessment for infusion reactions, infections, graft versus host disease or any other adverse events [ Time Frame: 6 months ]

The primary endpoint of this study is safety which will be evaluated by assessing the incidence of acute infusion reactions, infections, graft versus host disease.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 5, 2015)

• Assessment for improvement in gross motor function [ Time Frame: 6 months ]
  Assessment of improvement in gross motor function using validated tools.
• Assessment for improvement in fine motor function [ Time Frame: 6 months ]
  Assessment of fine motor function using validated tools.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cerebral Palsy

Intervention

Biological: sibling umbilical cord blood

All subjects will receive a single infusion of allogeneic sibling cord blood. The first six subjects will receive cord blood cells from an HLA-matched sibling. The following 9 subjects will receive cord blood cells from an HLA-mismatched (≥3/6 match) or matched sibling. Six of the 15 subjects must be treated with haplo-identical sibling CB. Duration of study participation will be six months from the time of CB infusion.

Study Arms

• Experimental: Matched related umbilical cord blood
  Six subjects will receive an infusion of HLA matched sibling umbilical cord blood cells.
  Intervention: Biological: sibling umbilical cord blood
• Experimental: Mismatched related umbilical cord blood
  Nine subjects will receive an infusion of HLA-mismatched (≥3/6 match) or matched sibling umbilical cord blood cells.
  Intervention: Biological: sibling umbilical cord blood

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 5, 2015): 15
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 2018
• Actual Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 6 Years (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: NCT02599207
• Other Study ID Numbers: Pro00065043
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Joanne Kurtzberg, MD, Duke University
• Study Sponsor: Joanne Kurtzberg, MD
• Collaborators: Not Provided

Investigators

• Principal Investigator: Joanne Kurtzberg, MD; Duke University
• Principal Investigator: Jessica Sun, MD; Duke University

• PRS Account: Duke University
• Verification Date: December 2019