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

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Joanne Kurtzberg, MD, Duke University Medical Center
Sponsor:
Collaborator:
The Marcus Foundation
Information provided by (Responsible Party):
Joanne Kurtzberg, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT02254863
First received: September 23, 2014
Last updated: June 27, 2017
Last verified: June 2017
  Purpose
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 Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Joanne Kurtzberg, MD, Duke University Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 12
Study Start Date: September 2014
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02254863

Contacts
Contact: Jennifer Baker, RN 844-800-2673 cordbloodtherapyinfo@dm.duke.edu
Contact: Kristine Edwards, RN 844-800-2673 cordbloodtherapyinfo@dm.duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27705
Contact: Jennifer Baker, RN       cordbloodtherapyinfo@dm.duke.edu   
Principal Investigator: Joanne Kurtzberg, MD         
Sub-Investigator: Jessica Sun, MD         
Sponsors and Collaborators
Joanne Kurtzberg, MD
The Marcus Foundation
Investigators
Principal Investigator: Joanne Kurtzberg, MD Duke University
  More Information

Responsible Party: Joanne Kurtzberg, MD, Professor of Pediatrics, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT02254863     History of Changes
Other Study ID Numbers: Pro00050198
Study First Received: September 23, 2014
Last Updated: June 27, 2017

Keywords provided by Joanne Kurtzberg, MD, Duke University Medical Center:
Adrenoleukodystrophy
Batten Disease
Hunter Syndrome
Krabbe
Metachromatic Leukodystrophy
ALD
MLD
PMD

Additional relevant MeSH terms:
Metabolic Diseases
Mucopolysaccharidoses
Brain Diseases
Adrenoleukodystrophy
Pick Disease of the Brain
Aphasia, Primary Progressive
Frontotemporal Dementia
Mannosidase Deficiency Diseases
alpha-Mannosidosis
Tay-Sachs Disease
Neuronal Ceroid-Lipofuscinoses
Mucopolysaccharidosis II
Sandhoff Disease
Leukodystrophy, Globoid Cell
Pelizaeus-Merzbacher Disease
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Leukodystrophy, Metachromatic
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Central Nervous System Diseases
Nervous System Diseases
Hereditary Central Nervous System Demyelinating Diseases

ClinicalTrials.gov processed this record on July 24, 2017