<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/NCT01711788</url>
  </required_header>
  <id_info>
    <org_study_id>IB-UCBT</org_study_id>
    <nct_id>NCT01711788</nct_id>
  </id_info>
  <brief_title>Intrabone Infusion of Umbilical Cord Blood Stem Cells</brief_title>
  <official_title>A New Approach to Improve Long-term Hematopoietic Recovery After Allogeneic Umbilical Cord Blood Transplantation in Children - Intrabone Infusion of Umbilical Cord Blood Stem Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Henrique Bittencourt, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Michel Duval, MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pierre Teira, MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sonia Cellot, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Isabelle Louis, PhD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Elie Haddad, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Marie-France Vachon, MScN</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Marion Cortier, PhD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Justine's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if the method of intrabone infusion of hematologic&#xD;
      stem cells can increase and accelerate hematopoietic reconstitution after umbilical cord&#xD;
      blood transplantation in pediatric patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Umbilical cord blood transplantation (UCBT) has been increasingly used to treat malignant and&#xD;
      non-malignant haematological, immunodeficiency and some metabolic diseases. UCBT offers the&#xD;
      advantages of easy procurement, no risk to donors, a reduced risk of transmitting infections,&#xD;
      immediate availability of cryopreserved units, and acceptable partial HLA mismatches.&#xD;
      However, patients treated with UCBT show delayed hematopoietic and immunological recoveries,&#xD;
      have higher rates of infection, and relapse from the original malignant disease, which can&#xD;
      all lead to life threatening problems. UCBT can also result in a higher rate of graft failure&#xD;
      compared to other hematopoietic stem cell transplantation (HSCT) sources. The problem of a&#xD;
      slower hematopoietic recovery post-UCBT has been addressed using a number of different&#xD;
      approaches in adult patients.In adults, use of intrabone injection of cord blood results in a&#xD;
      faster hematopoietic recovery in a phase II study. However, there is no clinical trial in&#xD;
      pediatric patients.&#xD;
&#xD;
      This study is addressed to determine if a change in the cord blood stem cell infusion method&#xD;
      can increase and accelerate hematopoietic reconstitution after UCBT in pediatric patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">October 3, 2017</completion_date>
  <primary_completion_date type="Actual">October 3, 2017</primary_completion_date>
  <phase>Phase 2</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>Platelet recovery rate</measure>
    <time_frame>at 100 days post- transplantation</time_frame>
    <description>First of seven days of untransfused platelet count higher than 20 x 10^9/L</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neutrophil recovery rate</measure>
    <time_frame>at 60 days post- transplantation</time_frame>
    <description>First of three days of absolute neutrophil count equal or higher than 0.5 x 10^9/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological reconstitution</measure>
    <time_frame>at 30, 60, 100, 180, and 360 days post- transplantation</time_frame>
    <description>Total number of T cells (and subpopulations), B and NK (natural killer) cells in peripheral blood at different time-points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Donor chimerism rate</measure>
    <time_frame>at 30, 60,100, and 180 days post-transplantation</time_frame>
    <description>Percentage of donor(s) cells in peripheral blood at different time-points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute GVHD (grade 2-4) rate</measure>
    <time_frame>at 180 days</time_frame>
    <description>Incidence of grade II-IV acute GVHD (Graft versus Host Disease)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infection rate (bacterial, viral, fungal and parasitic)</measure>
    <time_frame>at 180 days post-transplantation</time_frame>
    <description>Clinical and microbiological documented infections will be reported according to anatomic site, date of onset and microorganism</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free and overall survival</measure>
    <time_frame>at 2 years</time_frame>
    <description>Event-free survival is defined as the time interval between transplantation and relapse, graft rejection, death or last follow-up, whichever occurs first; Overall survival is defined as the time between transplantation and death or last follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse infections (grade and frequency)</measure>
    <time_frame>at one month post-transplantation</time_frame>
    <description>Toxicity will be assessed using the Common Terminology Criteria for Adverse Events v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>chronic GVHD</measure>
    <time_frame>at 2 years post-transplantation</time_frame>
    <description>Incidence of chronic GVHD (Graft versus Host Disease) will be scored according to NIH consensus on chronic GVHD</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Hematopoietic Stem Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>Intrabone umbilical cord blood tranplant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intrabone infusion of umbilical cord blood stem cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intrabone infusion of umbilical cord blood stem cells</intervention_name>
    <arm_group_label>Intrabone umbilical cord blood tranplant</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  One to 21 years of age;&#xD;
&#xD;
          -  More than 10 kg in weight;&#xD;
&#xD;
          -  Diagnosis of hematopoietic disorders (malignant or not) with an indication for&#xD;
             hematopoietic stem cell transplantation;&#xD;
&#xD;
          -  Absence of an HLA-identical related donor;&#xD;
&#xD;
          -  Availability of a single cord blood (CB) with at least 3 x 10^7 nucleated cells&#xD;
             (NCs)/kg (if HLA identical or 1 HLA-mismatch) or at least 4 x 10^7 NCs/kg (if a 2&#xD;
             HLA-mismatch) at freezing. Use of two CB units (&quot;double cord transplant&quot;) will be&#xD;
             allowed provided that: 1) a single CB unit fulfilling the above criteria is not&#xD;
             available; 2) a maximum of 2 HLA mismatch is present for each CB unit; and 3) a&#xD;
             minimum of 4 x 10^7 NCs/kg (as the sum for both CB units) is present at freezing.&#xD;
&#xD;
          -  A myeloablative-conditioning regimen;&#xD;
&#xD;
          -  A Lansky (for patients less than 16 years of age) or Karnofsky (for patients more than&#xD;
             16 years of age) score equal to or higher than 70%.&#xD;
&#xD;
          -  Adequate organ function as follows:&#xD;
&#xD;
          -  Cardiac (ejection fraction &gt; 50%);&#xD;
&#xD;
          -  Renal (serum creatinine within the normal range for age, and creatinine clearance or a&#xD;
             GFR &gt; 70 ml/min/1.73m2);&#xD;
&#xD;
          -  Hepatic (AST or ALT &lt; 5 x upper limit of normal for age);&#xD;
&#xD;
          -  Pulmonary (FEV1, FVC, and DLCO ≥ 50% by pulmonary function tests or, in children&#xD;
             unable to cooperate, no sign of dyspnea at rest, no exercise intolerance, no&#xD;
             supplementary oxygen therapy, and a normal pulmonary radiography or pulmonary scan);&#xD;
&#xD;
          -  No sign of uncontrolled systemic bacterial, fungal or viral infection;&#xD;
&#xD;
          -  Written informed consent by the patient or his/her legal guardian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-myeloablative conditioning;&#xD;
&#xD;
          -  Pregnancy or breastfeeding;&#xD;
&#xD;
          -  HIV positive serology;&#xD;
&#xD;
          -  Bone disease (e.g. osteopetrosis, osteogenesis imperfecta)&#xD;
&#xD;
          -  Previous autologous or allogeneic hematopoietic stem cell transplantation performed up&#xD;
             to one year before enrolment, except in the case of non-engraftment or early rejection&#xD;
             of a previous allogeneic stem cell transplantation.&#xD;
&#xD;
          -  Active skin infection at the site of intrabone injection.&#xD;
&#xD;
          -  History of intolerance/allergy to sedation medications or local anesthetics.&#xD;
&#xD;
          -  Contraindication to sedation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Henrique Bittencourt, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Justine's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Sainte-Justine</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3C1T5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>October 3, 2017</last_update_submitted>
  <last_update_submitted_qc>October 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>St. Justine's Hospital</investigator_affiliation>
    <investigator_full_name>Henrique Bittencourt, MD, PhD</investigator_full_name>
    <investigator_title>Hematologist - Oncologist</investigator_title>
  </responsible_party>
  <keyword>Hematopoietic stem cells</keyword>
  <keyword>Umbilical cord blood transplantation</keyword>
  <keyword>Intrabone infusion</keyword>
  <keyword>Platelet recovery</keyword>
  <keyword>Neutrophil recovery</keyword>
  <keyword>Pediatric patients</keyword>
  <!-- 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/NCT01711788
org study id: IB-UCBT
nct id: NCT01711788
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine if the method of intrabone infusion of hematologic
      stem cells can increase and accelerate hematopoietic reconstitution after umbilical cord
      blood transplantation in pediatric patients.
Umbilical cord blood transplantation (UCBT) has been increasingly used to treat malignant and
      non-malignant haematological, immunodeficiency and some metabolic diseases. UCBT offers the
      advantages of easy procurement, no risk to donors, a reduced risk of transmitting infections,
      immediate availability of cryopreserved units, and acceptable partial HLA mismatches.
      However, patients treated with UCBT show delayed hematopoietic and immunological recoveries,
      have higher rates of infection, and relapse from the original malignant disease, which can
      all lead to life threatening problems. UCBT can also result in a higher rate of graft failure
      compared to other hematopoietic stem cell transplantation (HSCT) sources. The problem of a
      slower hematopoietic recovery post-UCBT has been addressed using a number of different
      approaches in adult patients.In adults, use of intrabone injection of cord blood results in a
      faster hematopoietic recovery in a phase II study. However, there is no clinical trial in
      pediatric patients.

      This study is addressed to determine if a change in the cord blood stem cell infusion method
      can increase and accelerate hematopoietic reconstitution after UCBT in pediatric patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Platelet recovery rate
time frame: at 100 days post- transplantation
description: First of seven days of untransfused platelet count higher than 20 x 10^9/L
measure: Neutrophil recovery rate
time frame: at 60 days post- transplantation
description: First of three days of absolute neutrophil count equal or higher than 0.5 x 10^9/L
measure: Immunological reconstitution
time frame: at 30, 60, 100, 180, and 360 days post- transplantation
description: Total number of T cells (and subpopulations), B and NK (natural killer) cells in peripheral blood at different time-points
measure: Donor chimerism rate
time frame: at 30, 60,100, and 180 days post-transplantation
description: Percentage of donor(s) cells in peripheral blood at different time-points
measure: Acute GVHD (grade 2-4) rate
time frame: at 180 days
description: Incidence of grade II-IV acute GVHD (Graft versus Host Disease)
measure: Infection rate (bacterial, viral, fungal and parasitic)
time frame: at 180 days post-transplantation
description: Clinical and microbiological documented infections will be reported according to anatomic site, date of onset and microorganism
measure: Event-free and overall survival
time frame: at 2 years
description: Event-free survival is defined as the time interval between transplantation and relapse, graft rejection, death or last follow-up, whichever occurs first; Overall survival is defined as the time between transplantation and death or last follow-up
measure: Adverse infections (grade and frequency)
time frame: at one month post-transplantation
description: Toxicity will be assessed using the Common Terminology Criteria for Adverse Events v4.0
measure: chronic GVHD
time frame: at 2 years post-transplantation
description: Incidence of chronic GVHD (Graft versus Host Disease) will be scored according to NIH consensus on chronic GVHD
arm group label: Intrabone umbilical cord blood tranplant
arm group type: Experimental
description: Intrabone infusion of umbilical cord blood stem cells
intervention type: Procedure
intervention name: Intrabone infusion of umbilical cord blood stem cells
arm group label: Intrabone umbilical cord blood tranplant
criteria: 
gender: All
minimum age: 1 Year
maximum age: 21 Years
healthy volunteers: No
last name: Henrique Bittencourt, MD, PhD
role: Principal Investigator
affiliation: St. Justine's Hospital
facility: 
country: Canada
responsible party type: Sponsor-Investigator
investigator affiliation: St. Justine's Hospital
investigator full name: Henrique Bittencourt, MD, PhD
investigator title: Hematologist - Oncologist