<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02254863</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00050198</org_study_id>
    <nct_id>NCT02254863</nct_id>
  </id_info>
  <brief_title>UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells</brief_title>
  <acronym>DUOC-01</acronym>
  <official_title>Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases With Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Joanne Kurtzberg, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Marcus Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to determine the safety and feasibility of intrathecal&#xD;
      administration of DUOC-01 as an adjunctive therapy in patients with inborn errors of&#xD;
      metabolism who have evidence of early demyelinating disease in the central nervous system&#xD;
      (CNS) who are undergoing standard treatment with unrelated umbilical cord blood&#xD;
      transplantation (UCBT). The secondary objective of the study is to describe the efficacy of&#xD;
      UCBT with intrathecal administration of DUOC-01 in these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The inherited metabolic disorders (IMD) are a heterogeneous group of genetic diseases, most&#xD;
      of which involve a single gene mutation resulting in an enzyme defect. In the majority of&#xD;
      cases, the enzyme defect leads to the accumulation of substrates that are toxic and/or&#xD;
      interfere with normal cellular function. Often times, patients may appear normal at birth but&#xD;
      during infancy begin to exhibit disease manifestations, frequently including progressive&#xD;
      neurological deterioration due to absent or abnormal brain myelination. The ultimate result&#xD;
      is death in later infancy or childhood.&#xD;
&#xD;
      Currently, the only effective therapy to halt the neurologic progression of disease is&#xD;
      allogeneic hematopoietic stem cell transplantation (HSCT), which serves as a source of&#xD;
      permanent cellular ERT.3 However, one barrier to the success of this therapy is delayed&#xD;
      engraftment of donor cells in the CNS when administered through the intravenous route, which&#xD;
      is associated with ongoing disease progression over 2-4 months before stabilization. The&#xD;
      engraftment of donor cells in a patient with an IMD provides a constant source of enzyme&#xD;
      replacement, thereby slowing or halting the progression of disease.&#xD;
&#xD;
      This study will evaluate the safety of a potential new treatment for patients with certain&#xD;
      IMDs known to benefit from HSCT using allogeneic UCB donor cells. The new intervention,&#xD;
      intrathecal administration of UCB-derived oligodendrocyte-like cells (DUOC-01) will serve as&#xD;
      an adjunctive therapy to a standard UCB transplant. The goal of this therapy is to accelerate&#xD;
      delivery of donor cells to the CNS thereby bridging the gap between systemic transplant and&#xD;
      engraftment of cells in the CNS and preventing disease progression. The DUOC-01 cells and&#xD;
      cells used for HSCT will be derived from the same UCB donor unit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate for Infusional Toxicity</measure>
    <time_frame>24 hours after infusion</time_frame>
    <description>Will monitor for fever, vomiting, neck stiffness, seizures, changes in state of consciousness</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluate for Neuro Toxicity</measure>
    <time_frame>1 month after infusion</time_frame>
    <description>Perform computerized tomography (CT) scan to evaluate for bleeding, tumor formation, central nervous system generalized infiltration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy determination</measure>
    <time_frame>1-5 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Adrenoleukodystrophy</condition>
  <condition>Batten Disease</condition>
  <condition>Mucopolysaccharidosis II</condition>
  <condition>Leukodystrophy, Globoid Cell</condition>
  <condition>Leukodystrophy, Metachromatic</condition>
  <condition>Neimann Pick Disease</condition>
  <condition>Pelizaeus-Merzbacher Disease</condition>
  <condition>Sandhoff Disease</condition>
  <condition>Tay-Sachs Disease</condition>
  <condition>Brain Diseases, Metabolic, Inborn</condition>
  <condition>Alpha-Mannosidosis</condition>
  <condition>Sanfilippo Mucopolysaccharidoses</condition>
  <arm_group>
    <arm_group_label>Intrathecal administration of DUOC-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of DUOC-01, given intrathecally, between day 26 and 28 post unrelated cord blood transplant</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DUOC-01</intervention_name>
    <description>Intrathecal administration of DUOC-01</description>
    <arm_group_label>Intrathecal administration of DUOC-01</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must be age ≥1 week to &lt;21 years.&#xD;
&#xD;
          2. Patients must have one of the following inherited metabolic diseases detected by&#xD;
             enzyme or mutation analysis, and confirmed by repeat testing on a separately obtained&#xD;
             sample:&#xD;
&#xD;
             Adrenoleukodystrophy (ALD) Batten Disease Hunter Syndrome (MPS II) Krabbe disease&#xD;
             (Globoid Leukodystrophy) Metachromatic Leukodystrophy (MLD) Niemann Pick disease type&#xD;
             A or B Pelizaeus-Merzbacher disease (PMD) Sandhoff disease Tay Sachs disease. Alpha&#xD;
             Mannosidosis Sanfilippo (MPS III)&#xD;
&#xD;
          3. Patients must have neurologic evidence of their disease, either clinically or via&#xD;
             neuroimaging or neurophysiological testing. Examples of evidence of neurologic&#xD;
             involvement include, but are not limited to the following:&#xD;
&#xD;
               -  Abnormal EEG, Brainstem Auditory Evoked Response (BAER), and/or Visual Evoked&#xD;
                  Potentials (VEP).&#xD;
&#xD;
               -  Abnormal brain MRI, ie. increased Loes score (measure of white matter damage,&#xD;
                  demyelination, and brain atrophy) and/or abnormal corticospinal tracts as&#xD;
                  assessed by MRI with diffusion tensor imaging (DTI).&#xD;
&#xD;
               -  Three or more of the early clinical markers: problems sleeping, increased&#xD;
                  activity, behavior difficulties, seizure-like activity, chewing behavior,&#xD;
                  inappropriate bladder training, inappropriate bowel training.&#xD;
&#xD;
          4. Patients must have adequate organ function as measured by:&#xD;
&#xD;
               -  Renal: Serum creatinine &lt; 2.0 mg/dl&#xD;
&#xD;
               -  Hepatic: Hepatic transaminases (ALT/AST) &lt; 5 x normal, bilirubin &lt; 2.0 mg/dl&#xD;
                  (except in patients with Gilbert's disease or newborns with physiological or&#xD;
                  breast milk associated jaundice).&#xD;
&#xD;
               -  Cardiac: Normal cardiac function by echocardiogram or radionuclide scan&#xD;
                  (shortening fraction or ejection fraction&#xD;
&#xD;
                    -  80% of normal value for age). Patients with acquired or congenital&#xD;
                       cardiomyopathy may receive melphalan as a substitute for cyclophosphamide.&#xD;
&#xD;
               -  Pulmonary: Pulmonary function tests demonstrating FVC, FEV1, and DLCO ≥ 60% of&#xD;
                  predicted in patients who can complete the testing. If patient cannot perform&#xD;
                  PFT's, an O2 sat must be &gt;90% on room air.&#xD;
&#xD;
          5. Patients must not have a suitable fully matched, non-carrier sibling or related bone&#xD;
             marrow donor.&#xD;
&#xD;
          6. Patients must have an available, suitably matched, banked UCB unit in a&#xD;
             two-compartment configuration (see graft selection criteria in section 5.2).&#xD;
&#xD;
          7. Patients must have a performance status as follows: Lansky ≥ 40%, or Karnofsky ≥ 40%.&#xD;
&#xD;
          8. Patients must have a life expectancy of ≥ 6 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior organ, tissue, or stem cell transplant within 3 years of study entry.&#xD;
&#xD;
          2. Prior participation in any gene or regenerative cell therapy study.&#xD;
&#xD;
          3. Inability to have an MRI scan or lumbar puncture.&#xD;
&#xD;
          4. Intractable seizures.&#xD;
&#xD;
          5. Chronic aspiration.&#xD;
&#xD;
          6. Bleeding disorder.&#xD;
&#xD;
          7. Evidence of HIV infection or HIV positive serology.&#xD;
&#xD;
          8. Uncontrolled bacterial, viral, or fungal infection at the time of pre-UCBT&#xD;
             cytoreduction.&#xD;
&#xD;
          9. Inability to obtain patient's, parent's or legal guardian's consent.&#xD;
&#xD;
         10. Requirement of ventilatory support.&#xD;
&#xD;
         11. Pregnant or breastfeeding.&#xD;
&#xD;
         12. Active concurrent malignancy, or receiving concurrent radiotherapy, immunosuppressive&#xD;
             medications, or cytotoxic chemotherapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Week</minimum_age>
    <maximum_age>22 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joanne Kurtzberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sydney Crane, RN</last_name>
    <email>cordbloodtherapyinfo@dm.duke.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Erin Arbuckle</last_name>
    <email>cordbloodtherapyinfo@dm.duke.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sydney Crane, RN</last_name>
      <email>cordbloodtherapyinfo@dm.duke.edu</email>
    </contact>
    <investigator>
      <last_name>Joanne Kurtzberg, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jessica Sun, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <last_update_submitted>October 24, 2022</last_update_submitted>
  <last_update_submitted_qc>October 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Joanne Kurtzberg, MD</investigator_full_name>
    <investigator_title>Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Adrenoleukodystrophy</keyword>
  <keyword>Batten Disease</keyword>
  <keyword>Hunter Syndrome</keyword>
  <keyword>Krabbe</keyword>
  <keyword>Metachromatic Leukodystrophy</keyword>
  <keyword>ALD</keyword>
  <keyword>MLD</keyword>
  <keyword>PMD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Adrenoleukodystrophy</mesh_term>
    <mesh_term>Pick Disease of the Brain</mesh_term>
    <mesh_term>Mucopolysaccharidosis II</mesh_term>
    <mesh_term>Neuronal Ceroid-Lipofuscinoses</mesh_term>
    <mesh_term>Tay-Sachs Disease</mesh_term>
    <mesh_term>Sandhoff Disease</mesh_term>
    <mesh_term>Pelizaeus-Merzbacher Disease</mesh_term>
    <mesh_term>Brain Diseases, Metabolic</mesh_term>
    <mesh_term>Leukodystrophy, Globoid Cell</mesh_term>
    <mesh_term>Brain Diseases, Metabolic, Inborn</mesh_term>
    <mesh_term>Niemann-Pick Diseases</mesh_term>
    <mesh_term>Niemann-Pick Disease, Type A</mesh_term>
    <mesh_term>Niemann-Pick Disease, Type C</mesh_term>
    <mesh_term>Leukodystrophy, Metachromatic</mesh_term>
    <mesh_term>Mucopolysaccharidoses</mesh_term>
    <mesh_term>Mannosidase Deficiency Diseases</mesh_term>
    <mesh_term>alpha-Mannosidosis</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02254863
org study id: Pro00050198
nct id: NCT02254863
lead sponsor: 
collaborator: 
has dmc: Yes
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluate for Infusional Toxicity
time frame: 24 hours after infusion
description: Will monitor for fever, vomiting, neck stiffness, seizures, changes in state of consciousness
measure: Evaluate for Neuro Toxicity
time frame: 1 month after infusion
description: Perform computerized tomography (CT) scan to evaluate for bleeding, tumor formation, central nervous system generalized infiltration
measure: Efficacy determination
time frame: 1-5 years
description: 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.
arm group label: Intrathecal administration of DUOC-01
arm group type: Experimental
description: Administration of DUOC-01, given intrathecally, between day 26 and 28 post unrelated cord blood transplant
intervention type: Biological
intervention name: DUOC-01
description: Intrathecal administration of DUOC-01
arm group label: Intrathecal administration of DUOC-01
criteria: 
gender: All
minimum age: 1 Week
maximum age: 22 Years
healthy volunteers: No
last name: Joanne Kurtzberg, MD
role: Principal Investigator
affiliation: Duke University
last name: Sydney Crane, RN
email: cordbloodtherapyinfo@dm.duke.edu
last name: Erin Arbuckle
email: cordbloodtherapyinfo@dm.duke.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Joanne Kurtzberg, MD
investigator title: Professor of Pediatrics
mesh term: Brain Diseases
mesh term: Adrenoleukodystrophy
mesh term: Pick Disease of the Brain
mesh term: Mucopolysaccharidosis II
mesh term: Neuronal Ceroid-Lipofuscinoses
mesh term: Tay-Sachs Disease
mesh term: Sandhoff Disease
mesh term: Pelizaeus-Merzbacher Disease
mesh term: Brain Diseases, Metabolic
mesh term: Leukodystrophy, Globoid Cell
mesh term: Brain Diseases, Metabolic, Inborn
mesh term: Niemann-Pick Diseases
mesh term: Niemann-Pick Disease, Type A
mesh term: Niemann-Pick Disease, Type C
mesh term: Leukodystrophy, Metachromatic
mesh term: Mucopolysaccharidoses
mesh term: Mannosidase Deficiency Diseases
mesh term: alpha-Mannosidosis
mesh term: Metabolic Diseases