The primary objective of the study is to determine the safety and feasibility of intrathecal administration of DUOC-01 in patients who are undergoing standard treatment with umbilical cord blood transplant (UCBT) for inborn errors of metabolism and who have evidence of early demyelinating disease in the central nervous system (CNS). The secondary objective of the study is to describe the efficacy of UCBT with intrathecal administration of DUOC-01 in these patients.
The inherited metabolic disorders (IMD) are a 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 buildup of substances 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 symptoms, 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 slow or halt this neurologic decline is allogeneic hematopoietic stem cell transplantation (HSCT). 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. However, one barrier to the success of HSCT is the slower engraftment of donor cells in the central nervous system (CNS), which is associated with ongoing disease progression over 2-4 months before stabilization. This study will evaluate the safety of an additional cell therapy for patients who are receiving HSCT using umbilical cord blood (UCB) cells from an allogeneic (non-self) donor for treatment of an IMD that is known to benefit from HSCT. The additional cell therapy, UCB-derived oligodendrocyte-like cells (DUOC-01), will serve as a supplementary therapy to a standard UCB transplant. DUOC-01 is administered intrathecally (injected into the spinal fluid) after transplant. The goal of this therapy is to accelerate delivery of donor cells to the CNS, thereby bridging the gap between the time from UCB transplant to engraftment of the UCB cells in the CNS, with the goal of preventing disease progression. This study is only performed at Duke University Medical Center and only patients who are medically eligible for a UCB transplant will be enrolled.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Intrathecal administration of DUOC-01
Duke University Medical Center
Durham, North Carolina, United States
RECRUITINGEvaluate for Infusional Toxicity
Will monitor for fever, vomiting, neck stiffness, seizures, changes in state of consciousness
Time frame: 24 hours after infusion
Evaluate for Neuro Toxicity
Perform computerized tomography (CT) scan to evaluate for bleeding, tumor formation, central nervous system generalized infiltration
Time frame: 1 month after infusion
Efficacy determination
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.
Time frame: 1-5 years
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