<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/NCT02204904</url>
  </required_header>
  <id_info>
    <org_study_id>ALD-103</org_study_id>
    <nct_id>NCT02204904</nct_id>
  </id_info>
  <brief_title>Observational Study to Evaluate Allogeneic HSCT Outcomes for Cerebral Adrenoleukodystrophy (CALD)</brief_title>
  <official_title>A Prospective and Retrospective Data Collection Study to Evaluate Outcomes in Males ≤17 Years of Age Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Cerebral Adrenoleukodystrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>bluebird bio</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>bluebird bio</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study ALD-103 will be a multi-site, global, prospective and retrospective data collection&#xD;
      study that is designed to evaluate outcomes of allo-HSCT in male subjects with CALD ≤17 years&#xD;
      of age.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sufficient enrollment for Month 24 safety and efficacy endpoints&#xD;
  </why_stopped>
  <start_date type="Actual">April 2015</start_date>
  <completion_date type="Actual">December 6, 2019</completion_date>
  <primary_completion_date type="Actual">December 6, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of transplant-related mortality (TRM).</measure>
    <time_frame>Through 100 and 365 days post allo-HSC infusion</time_frame>
    <description>TRM is defined as death due to any transplantation-related cause other than disease progression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and timing of neutrophil engraftment.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and timing of platelet engraftment</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of engraftment failure or allograft rejection.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of primary donor-derived chimerism of ≥50%.</measure>
    <time_frame>by 100 days post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency and severity of Criteria for Adverse Events (CTCAE) ≥Grade 3 AEs, CTCAE ≥Grade 3 infections, and all SAEs.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of subjects who experience either ≥Grade II acute (Graft versus Host Disease) GVHD or chronic GVHD.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of ≥Grade II acute GVHD.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of chronic GVHD.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of emergency room visits.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number and duration of intensive care unit stay.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number and duration of in-patient hospitalization.</measure>
    <time_frame>1-48 (± 1) months post allo-HSC infusion</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Major Functional Disabilities (MFDs).</measure>
    <time_frame>1-48 (± 2) months post allo-HSC infusion</time_frame>
    <description>MFDs is defined as any of the following: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Loes score</measure>
    <time_frame>1-48 (± 2) months post allo-HSC infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Neurological Function Score (NFS)</measure>
    <time_frame>1-48 (± 2) months post allo-HSC infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency and timing of resolution of gadolinium enhancement on MRI, if applicable</measure>
    <time_frame>1-48 (± 2) months post allo-HSC infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MFD-free survival</measure>
    <time_frame>48 (± 2) months post allo-HSC infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>48 (± 2) months post allo-HSC infusion</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">59</enrollment>
  <condition>X-Linked Adrenoleukodystrophy (X-ALD)</condition>
  <condition>Cerebral Adrenoleukodystrophy (CALD)</condition>
  <condition>Adrenoleukodystrophy (ALD)</condition>
  <arm_group>
    <arm_group_label>Allo-HSCT prospective</arm_group_label>
    <description>Subjects who will be consented before they received an allo-HSC infusion. They will be consented and enrolled on the study during the Screening Period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Allo-HSCT partial prospective/retrospective</arm_group_label>
    <description>Subjects who will be consented after they received an allo-HSC infusion but before they reach 24 months post-infusion on study. Subjects in this cohort will participate prospectively in at least the Month 24 Visit in order to obtain prospective on-study data for this and all visits after Month 24</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Allo-HSCT retrospective</arm_group_label>
    <description>Subjects who received an allo-HSC infusion on or after January 1, 2013 and died before study data collection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Allo-HSCT</intervention_name>
    <description>Allogeneic Hematopoietic Stem Cell Transplantation</description>
    <arm_group_label>Allo-HSCT partial prospective/retrospective</arm_group_label>
    <arm_group_label>Allo-HSCT prospective</arm_group_label>
    <arm_group_label>Allo-HSCT retrospective</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Boys aged 17 or younger receiving allogeneic hematopoietic stem cell transplantation for&#xD;
        the treatment of cerebral adrenoleukodystrophy prospectively or partially&#xD;
        prospective/retrospective&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provide informed consent from a competent custodial parent or guardian with legal&#xD;
             capacity to execute a local Institutional Review Board (IRB)/Independent Ethics&#xD;
             Committee (IEC) approved consent. In addition, informed assent will be sought from&#xD;
             capable subjects, in accordance with the directive of the institution's IRB/IEC and&#xD;
             all other local requirements.&#xD;
&#xD;
          2. Be male and ≤17 years of age at the time of treatment, for retrospective and partial&#xD;
             prospective/retrospective subjects, or at the time of parental/guardian consent and,&#xD;
             where appropriate, subject assent, for prospective subjects.&#xD;
&#xD;
          3. Have a confirmed diagnosis of CALD as defined by abnormal VLCFA profile and cerebral&#xD;
             lesion on brain MRI.&#xD;
&#xD;
          4. Depending on the cohort, the subject must:&#xD;
&#xD;
               -  Be scheduled for allo-HSCT evaluation at a study site (prospective cohort only),&#xD;
&#xD;
               -  Have received an allo-HSC infusion and be consented in time to complete the Month&#xD;
                  24 Visit on study (partial prospective/retrospective cohort only), or&#xD;
&#xD;
               -  Have received their most recent allo-HSC infusion on or after January 1, 2013&#xD;
                  (retrospective cohort only).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with a gene therapy product.&#xD;
&#xD;
          2. Receipt of an experimental transplantation procedure.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elizabeth McNeil, MD MSc</last_name>
    <role>Study Director</role>
    <affiliation>bluebird bio, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital/Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Austral</name>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H3H 2R9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Leipzig</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale Pediatrico Bambine Gesú</name>
      <address>
        <city>Roma</city>
        <zip>00165</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Maxima Center for Pediatric Oncology (PMC)</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Ormond Street Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Manchester University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Canada</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>May 19, 2020</last_update_submitted>
  <last_update_submitted_qc>May 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>X-linked Adrenoleukodystrophy</keyword>
  <keyword>Hematopoietic Stem Cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adrenoleukodystrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>March 4, 2022</submitted>
    <returned>May 23, 2022</returned>
  </pending_results>
  <!-- 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/NCT02204904
org study id: ALD-103
nct id: NCT02204904
lead sponsor: 
has dmc: No
Study ALD-103 will be a multi-site, global, prospective and retrospective data collection
      study that is designed to evaluate outcomes of allo-HSCT in male subjects with CALD ≤17 years
      of age.
observational model: Cohort
time perspective: Other
measure: Incidence of transplant-related mortality (TRM).
time frame: Through 100 and 365 days post allo-HSC infusion
description: TRM is defined as death due to any transplantation-related cause other than disease progression.
measure: Incidence and timing of neutrophil engraftment.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence and timing of platelet engraftment
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of engraftment failure or allograft rejection.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of primary donor-derived chimerism of ≥50%.
time frame: by 100 days post allo-HSC infusion
measure: Frequency and severity of Criteria for Adverse Events (CTCAE) ≥Grade 3 AEs, CTCAE ≥Grade 3 infections, and all SAEs.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Proportion of subjects who experience either ≥Grade II acute (Graft versus Host Disease) GVHD or chronic GVHD.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of ≥Grade II acute GVHD.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of chronic GVHD.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Number of emergency room visits.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Number and duration of intensive care unit stay.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Number and duration of in-patient hospitalization.
time frame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of Major Functional Disabilities (MFDs).
time frame: 1-48 (± 2) months post allo-HSC infusion
description: MFDs is defined as any of the following: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement.
measure: Change from Baseline in Loes score
time frame: 1-48 (± 2) months post allo-HSC infusion
measure: Change from Baseline in Neurological Function Score (NFS)
time frame: 1-48 (± 2) months post allo-HSC infusion
measure: Frequency and timing of resolution of gadolinium enhancement on MRI, if applicable
time frame: 1-48 (± 2) months post allo-HSC infusion
measure: MFD-free survival
time frame: 48 (± 2) months post allo-HSC infusion
measure: Overall survival
time frame: 48 (± 2) months post allo-HSC infusion
arm group label: Allo-HSCT prospective
description: Subjects who will be consented before they received an allo-HSC infusion. They will be consented and enrolled on the study during the Screening Period.
arm group label: Allo-HSCT partial prospective/retrospective
description: Subjects who will be consented after they received an allo-HSC infusion but before they reach 24 months post-infusion on study. Subjects in this cohort will participate prospectively in at least the Month 24 Visit in order to obtain prospective on-study data for this and all visits after Month 24
arm group label: Allo-HSCT retrospective
description: Subjects who received an allo-HSC infusion on or after January 1, 2013 and died before study data collection.
intervention type: Genetic
intervention name: Allo-HSCT
description: Allogeneic Hematopoietic Stem Cell Transplantation
arm group label: Allo-HSCT partial prospective/retrospective
arm group label: Allo-HSCT prospective
arm group label: Allo-HSCT retrospective
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: N/A
maximum age: 17 Years
healthy volunteers: No
last name: Elizabeth McNeil, MD MSc
role: Study Director
affiliation: bluebird bio, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Argentina
country: Canada
country: Germany
country: Italy
country: Netherlands
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Adrenoleukodystrophy
sharing ipd: Yes
submitted: March 4, 2022
returned: May 23, 2022