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UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells (DUOC-01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02254863
Recruitment Status : Recruiting
First Posted : October 2, 2014
Last Update Posted : December 14, 2021
The Marcus Foundation
Information provided by (Responsible Party):
Joanne Kurtzberg, MD, Duke University

Brief Summary:
The primary objective of the study is to determine the safety and feasibility of intrathecal administration of DUOC-01 as an adjunctive therapy in patients with inborn errors of metabolism who have evidence of early demyelinating disease in the central nervous system (CNS) who are undergoing standard treatment with unrelated umbilical cord blood transplantation (UCBT). The secondary objective of the study is to describe the efficacy of UCBT with intrathecal administration of DUOC-01 in these patients.

Condition or disease Intervention/treatment Phase
Adrenoleukodystrophy Batten Disease Mucopolysaccharidosis II Leukodystrophy, Globoid Cell Leukodystrophy, Metachromatic Neimann Pick Disease Pelizaeus-Merzbacher Disease Sandhoff Disease Tay-Sachs Disease Brain Diseases, Metabolic, Inborn Alpha-Mannosidosis Sanfilippo Mucopolysaccharidoses Biological: DUOC-01 Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : September 2014
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Arm Intervention/treatment
Experimental: Intrathecal administration of DUOC-01
Administration of DUOC-01, given intrathecally, between day 26 and 28 post unrelated cord blood transplant
Biological: DUOC-01
Intrathecal administration of DUOC-01

Primary Outcome Measures :
  1. Evaluate for Infusional Toxicity [ Time Frame: 24 hours after infusion ]
    Will monitor for fever, vomiting, neck stiffness, seizures, changes in state of consciousness

  2. 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

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must be age ≥1 week to <21 years.
  2. Patients must have one of the following inherited metabolic diseases detected by enzyme or mutation analysis, and confirmed by repeat testing on a separately obtained sample:

    Adrenoleukodystrophy (ALD) Batten Disease Hunter Syndrome (MPS II) Krabbe disease (Globoid Leukodystrophy) Metachromatic Leukodystrophy (MLD) Niemann Pick disease type A or B Pelizaeus-Merzbacher disease (PMD) Sandhoff disease Tay Sachs disease. Alpha Mannosidosis Sanfilippo (MPS III)

  3. Patients must have neurologic evidence of their disease, either clinically or via neuroimaging or neurophysiological testing. Examples of evidence of neurologic involvement include, but are not limited to the following:

    • Abnormal EEG, Brainstem Auditory Evoked Response (BAER), and/or Visual Evoked Potentials (VEP).
    • Abnormal brain MRI, ie. increased Loes score (measure of white matter damage, demyelination, and brain atrophy) and/or abnormal corticospinal tracts as assessed by MRI with diffusion tensor imaging (DTI).
    • Three or more of the early clinical markers: problems sleeping, increased activity, behavior difficulties, seizure-like activity, chewing behavior, inappropriate bladder training, inappropriate bowel training.
  4. Patients must have adequate organ function as measured by:

    • Renal: Serum creatinine < 2.0 mg/dl
    • Hepatic: Hepatic transaminases (ALT/AST) < 5 x normal, bilirubin < 2.0 mg/dl (except in patients with Gilbert's disease or newborns with physiological or breast milk associated jaundice).
    • Cardiac: Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction

      • 80% of normal value for age). Patients with acquired or congenital cardiomyopathy may receive melphalan as a substitute for cyclophosphamide.
    • Pulmonary: Pulmonary function tests demonstrating FVC, FEV1, and DLCO ≥ 60% of predicted in patients who can complete the testing. If patient cannot perform PFT's, an O2 sat must be >90% on room air.
  5. Patients must not have a suitable fully matched, non-carrier sibling or related bone marrow donor.
  6. Patients must have an available, suitably matched, banked UCB unit in a two-compartment configuration (see graft selection criteria in section 5.2).
  7. Patients must have a performance status as follows: Lansky ≥ 40%, or Karnofsky ≥ 40%.
  8. Patients must have a life expectancy of ≥ 6 months.

Exclusion Criteria:

  1. Prior organ, tissue, or stem cell transplant within 3 years of study entry.
  2. Prior participation in any gene or regenerative cell therapy study.
  3. Inability to have an MRI scan or lumbar puncture.
  4. Intractable seizures.
  5. Chronic aspiration.
  6. Bleeding disorder.
  7. Evidence of HIV infection or HIV positive serology.
  8. Uncontrolled bacterial, viral, or fungal infection at the time of pre-UCBT cytoreduction.
  9. Inability to obtain patient's, parent's or legal guardian's consent.
  10. Requirement of ventilatory support.
  11. Pregnant or breastfeeding.
  12. Active concurrent malignancy, or receiving concurrent radiotherapy, immunosuppressive medications, or cytotoxic chemotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02254863

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Contact: Sydney Crane, RN
Contact: Erin Arbuckle

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United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27705
Contact: Sydney Crane, RN   
Principal Investigator: Joanne Kurtzberg, MD         
Sub-Investigator: Jessica Sun, MD         
Sponsors and Collaborators
Joanne Kurtzberg, MD
The Marcus Foundation
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Principal Investigator: Joanne Kurtzberg, MD Duke University
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Responsible Party: Joanne Kurtzberg, MD, Professor of Pediatrics, Duke University Identifier: NCT02254863    
Other Study ID Numbers: Pro00050198
First Posted: October 2, 2014    Key Record Dates
Last Update Posted: December 14, 2021
Last Verified: December 2021
Keywords provided by Joanne Kurtzberg, MD, Duke University:
Batten Disease
Hunter Syndrome
Metachromatic Leukodystrophy
Additional relevant MeSH terms:
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Brain Diseases
Pick Disease of the Brain
Neuronal Ceroid-Lipofuscinoses
Mucopolysaccharidosis II
Tay-Sachs Disease
Sandhoff Disease
Brain Diseases, Metabolic
Pelizaeus-Merzbacher Disease
Leukodystrophy, Globoid Cell
Brain Diseases, Metabolic, Inborn
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Leukodystrophy, Metachromatic
Mannosidase Deficiency Diseases
Metabolic Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Central Nervous System Diseases
Nervous System Diseases
Hereditary Central Nervous System Demyelinating Diseases
Demyelinating Diseases