UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells (DUOC-01)
Leukodystrophy, Globoid Cell
Neimann Pick Disease
Brain Diseases, Metabolic, Inborn
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases With Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells|
- Evaluate for Infusional Toxicity [ Time Frame: 24 hours after infusion ]Will monitor for fever, vomiting, neck stiffness, seizures, changes in state of consciousness
- Evaluate for Neuro Toxicity [ Time Frame: 1 month after infusion ]Perform computerized tomography (CT) scan to evaluate for bleeding, tumor formation, central nervous system generalized infiltration
- Efficacy determination [ Time Frame: 1-5 years ]Perform standard of care follow-up evaluations to include brain magnetic resonance imaging (MRI) with diffuse tensor imaging (DTI), Electroencephalography (EEG), nerve conduction, brainstem auditory evoked response (BAER), visual evoked potential (VEP) and neurocognitive testing. Bench mark results against historical controls previously transplanted by our institution for the past 20 years.
|Study Start Date:||September 2014|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Experimental: Intrathecal administration of DUOC-01
Administration of DUOC-01, given intrathecally, between day 26 and 28 post unrelated cord blood transplant
Intrathecal administration of DUOC-01
The inherited metabolic disorders (IMD) are a heterogeneous group of genetic diseases, most of which involve a single gene mutation resulting in an enzyme defect. In the majority of cases, the enzyme defect leads to the accumulation of substrates that are toxic and/or interfere with normal cellular function. Often times, patients may appear normal at birth but during infancy begin to exhibit disease manifestations, frequently including progressive neurological deterioration due to absent or abnormal brain myelination. The ultimate result is death in later infancy or childhood.
Currently, the only effective therapy to halt the neurologic progression of disease is allogeneic hematopoietic stem cell transplantation (HSCT), which serves as a source of permanent cellular ERT.3 However, one barrier to the success of this therapy is delayed engraftment of donor cells in the CNS when administered through the intravenous route, which is associated with ongoing disease progression over 2-4 months before stabilization. The engraftment of donor cells in a patient with an IMD provides a constant source of enzyme replacement, thereby slowing or halting the progression of disease.
This study will evaluate the safety of a potential new treatment for patients with certain IMDs known to benefit from HSCT using allogeneic UCB donor cells. The new intervention, intrathecal administration of UCB-derived oligodendrocyte-like cells (DUOC-01) will serve as an adjunctive therapy to a standard UCB transplant. The goal of this therapy is to accelerate delivery of donor cells to the CNS thereby bridging the gap between systemic transplant and engraftment of cells in the CNS and preventing disease progression. The DUOC-01 cells and cells used for HSCT will be derived from the same UCB donor unit.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02254863
|Contact: Jennifer Baker, RNfirstname.lastname@example.org|
|Contact: Kristine Edwards, RNemail@example.com|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27705|
|Contact: Jennifer Baker, RN firstname.lastname@example.org|
|Principal Investigator: Joanne Kurtzberg, MD|
|Sub-Investigator: Jessica Sun, MD|
|Principal Investigator:||Joanne Kurtzberg, MD||Duke University|