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Trial record 2 of 31 for:    kurtzberg

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 : November 24, 2020
The Marcus Foundation
Information provided by (Responsible Party):
Joanne Kurtzberg, MD, Duke University

Tracking Information
First Submitted Date  ICMJE September 23, 2014
First Posted Date  ICMJE October 2, 2014
Last Update Posted Date November 24, 2020
Study Start Date  ICMJE September 2014
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2014)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2014)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells
Official Title  ICMJE Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases With Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Biological: DUOC-01
Intrathecal administration of DUOC-01
Study Arms  ICMJE Experimental: Intrathecal administration of DUOC-01
Administration of DUOC-01, given intrathecally, between day 26 and 28 post unrelated cord blood transplant
Intervention: Biological: DUOC-01
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 29, 2014)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 22 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bethany Kistler, RN 919-668-8428
Contact: Sydney Crane, RN
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02254863
Other Study ID Numbers  ICMJE Pro00050198
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Joanne Kurtzberg, MD, Duke University
Study Sponsor  ICMJE Joanne Kurtzberg, MD
Collaborators  ICMJE The Marcus Foundation
Investigators  ICMJE
Principal Investigator: Joanne Kurtzberg, MD Duke University
PRS Account Duke University
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP