A Study of UCB and MSCs in Children With CP: ACCeNT-CP

Study Overview
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Brief Summary
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The main purpose of this study is to estimate change in motor function 12 months after treatment with a single dose of allogeneic umbilical cord blood (AlloCB) or repeated doses of umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy. In addition, this study will contribute much needed data to the clinical trials community on the natural history of the motor function in CP over short-term (less than 1 year) time periods relevant to the conduct of clinical trials and assess the safety of AlloCB and hCT-MSC infusion in children with cerebral palsy.

Detailed Description
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This study is a phase I/II, prospective, randomized, open-label trial designed to determine the effect size of change in GMFM-66 score in subjects treated with hCT-MSC or allogeneic CB and assess the safety of repeated doses of hCT-MSC in children with cerebral palsy. Children ages 2-5 years with cerebral palsy due to hypoxic ischemic encephalopathy, stroke, or periventricular leukomalacia may be eligible to participate. All participants will ultimately be treated with an allogeneic cell product at some point during the study. Participants will be randomized to one of three arms: (1) the AlloCB arm will receive one allogeneic CB infusion at the baseline visit; (2) the MSC arm will receive three hCT-MSC infusions, one each at baseline, three months, and six months; (3) the natural history arm will not receive an infusion at baseline but will receive an allogeneic CB infusion at 12 months. Motor outcome measures will be assessed at baseline, six-months, and one-year time points. Safety will be evaluated at each infusion visit and remotely for an additional 12 months after the final visit. Duration of study participation will be 24 months from the time of baseline visit. Randomization to treatment arms will be stratified by GMFCS level at study entry and etiology of CP (Stroke vs. Other).

Official Title
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A Phase I/II Study of Allogeneic Umbilical Cord Blood and Umbilical Cord Tissue-Derived Mesenchymal Stromal Cell Infusions in Children With Cerebral Palsy

Conditions
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Cerebral Palsy

Intervention / Treatment
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* Biological: Infusion of allogeneic umbilical cord blood
* Biological: Infusion of MSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥24 months and ≤60 months adjusted age at the time of enrollment. Diagnosis: Unilateral or bilateral hypertonic cerebral palsy secondary to in utero or perinatal stroke/hemorrhage, hypoxic ischemic encephalopathy (including, but not limited to, birth asphyxia), and/or periventricular leukomalacia. Performance status: Gross Motor Function Classification Score levels I - IV Review of brain imaging (obtained as standard of care prior to study entry) does not suggest a genetic condition or brain malformation. Legal authorized representative consent. Exclusion Criteria: Available qualified autologous cord blood unit. Hypotonic or ataxic cerebral palsy without spasticity. Autism and autistic spectrum disorders. Hypsarrhythmia. Legally blind Intractable seizures causing epileptic encephalopathy. Evidence of a progressive neurologic disease. Has an active, uncontrolled systemic infection or documentation of HIV+ status. Known genetic disease or phenotypic evidence of a genetic disease on physical exam. Concurrent genetic or acquired disease or comorbidity(ies) that could require a future allogeneic stem cell transplant. Requires ventilatory support, including home ventilator, CPAP, BiPAP, or supplemental oxygen. 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. Possible immunosuppression, defined as WBC <3,000 cells/mL or absolute lymphocyte count (ALC) <1500 with abnormal T-cell subsets. Patient's medical condition does not permit safe travel. Previously received any form of cellular therapy.

Ages Eligible for Study
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Minimum Age: 24 Months
Maximum Age: 60 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic Umbilical Cord Blood<br>Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells | Biological: Infusion of allogeneic umbilical cord blood<br>* Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.<br>|
| Experimental: Cord Tissue Mesenchymal Stromal Cells<br>Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors | Biological: Infusion of MSCs<br>* Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).<br>|
| Active Comparator: Natural History<br>Subjects will not receive any study product infusion until after the 12 month assessment. At the 12 month visit, they will receive an infusion of allogeneic umbilical cord blood cells so that all study participants will receive some type of cellular therapy. | Biological: Infusion of allogeneic umbilical cord blood<br>* Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gross Motor Function Measure (GMFM-66) in Excess of Expected Change | GMFM-66 is used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. The primary endpoint in this study was computed from the GMFM-66 score in three steps: 1) The observed change in motor function from Baseline to Month 12 was calculated (positive values indicate improvement, negative values indicate reduction, and zero indicates no change) for each participant; and 2) The expected change in motor function was determined for each participant based on published growth curves; and 3) The expected change in GMFM-66 was subtracted from the observed change to yield the final primary outcome. Positive values indicate a greater change than would be expected, zero indicates change as expected, and negative values indicate a smaller amount of change than would be expected. | Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | The secondary endpoint of this study is the number of adverse events occurring over a 12-month period post-treatment with hCT-MSC or AlloCB. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CP, Cerebral Palsy, Stem Cell, Cord Blood, MSCs