<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/NCT03019809</url>
  </required_header>
  <id_info>
    <org_study_id>WAS_PG 2016</org_study_id>
    <nct_id>NCT03019809</nct_id>
  </id_info>
  <brief_title>A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients</brief_title>
  <official_title>A Trial of Plerixafor With G-CSF as Additional Agents in Conditioning Regimen for Prevention of Graft Failure After Transplantation With TCR Alpha/Beta Grafts Depletion in Patients With Wiskott-Aldrich Syndrome.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federal Research Institute of Pediatric Hematology, Oncology and Immunology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federal Research Institute of Pediatric Hematology, Oncology and Immunology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Treatment Study to assess of safety and efficiency of conditioning with Plerixafor and G-CSF&#xD;
      as additional agents for prevention of graft failure after transplantation with TCR&#xD;
      alpha/beta grafts depletion in patient with Wiskott-Aldrich syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Severe graft dysfunction, such as the degree of donor chimerism predominantly in the myeloid&#xD;
      compartment is one of major problem in patients with Wiskott-Aldrich syndrome (WAS),&#xD;
      especially after hematopoietic stem cell transplantation (HSCT) from alternative donor. It&#xD;
      often leads to the development of severe thrombocytopenia or even transplants rejection. In&#xD;
      this study the hypothesis is that the use of plerixafor and G-CSF as additional agents in&#xD;
      conditioning regimen would offers advantages due to lowing risk of mixed chimerism after&#xD;
      HSCT. This effect is based on the fact that simultaneous use of plerixafor with G-CSF is&#xD;
      efficient in inducing stem cell release and opening of bone marrow (BM) niches. Moreover,&#xD;
      stem cell release probably leads to liberation of host stem cells from the anti-apoptotic&#xD;
      effects of the BM stroma for the more powerful effect of chemotherapy.&#xD;
&#xD;
      In this study, the investigators use TCR alpha/beta grafts depletion of the grafts as basic&#xD;
      technology for HSCT from haploidentical and unrelated donors approved in Institution.&#xD;
&#xD;
      Thus, the purpose of this study is to evaluate the safety and efficiency of myeloablative&#xD;
      conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure&#xD;
      after transplantation with TCR alpha/beta grafts depletion in patients with Wiskott-Aldrich&#xD;
      syndrome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 2016</start_date>
  <completion_date type="Anticipated">July 2019</completion_date>
  <primary_completion_date type="Actual">December 2018</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>Event free survival (EFS)</measure>
    <time_frame>24 months</time_frame>
    <description>The EFS probability compared with historical control. We mean event as patient's death, second transplantation or persistence of severe thrombocytopenia</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>24 months</time_frame>
    <description>The OS probability compared with historical control.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with full/mixed donor chimerism</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation of the percentage of patients with the full/mixed donor chimerism (whole blood and CD3+ lineage). In addition, patients will be divided in accordance with % of donors cells: &gt;95%; 50%-95%; 10%-49%; &lt;10%. All data will be compared with historical control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transplant related mortality (TRM)</measure>
    <time_frame>24 months</time_frame>
    <description>The TRM probability compared with historical control.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe thrombocytopenia (ST)</measure>
    <time_frame>24 months</time_frame>
    <description>The ST probability after HSCT compared with historical control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Autoimmune complications (AC)</measure>
    <time_frame>24 months</time_frame>
    <description>The AC probability after HSCT compared with historical control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Graft Versus Host Diseases (aGVHD)</measure>
    <time_frame>12 months</time_frame>
    <description>Cumulative Incidence and severity of aGVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic Graft Versus Host Diseases (cGVHD)</measure>
    <time_frame>24 months</time_frame>
    <description>Cumulative Incidence and severity of cGVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plerixafor related complications (PRC)</measure>
    <time_frame>2 week</time_frame>
    <description>PRC: severity, features, incidence</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Wiskott-Aldrich Syndrome</condition>
  <condition>Hematopoietic Stem Cell Transplantation</condition>
  <condition>Graft Failure</condition>
  <arm_group>
    <arm_group_label>Plerixafor/G-CSF for HSCT conditioning</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Myeloablative conditioning regimen with Plerixafor and G-CSF as addition agents before stem cell transplantation in WAS patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>G-CSF for Conditioning before HSCT.</intervention_name>
    <description>Mobilization of hematopoietic stem (HSC) into circulation</description>
    <arm_group_label>Plerixafor/G-CSF for HSCT conditioning</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Plerixafor for Conditioning before HSCT.</intervention_name>
    <description>Directed inhibition of CXC chemokine receptor type 4 (CXCR4) for opening enough BM niches for adequate donor HSC engraftment.</description>
    <arm_group_label>Plerixafor/G-CSF for HSCT conditioning</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged ≥ 1 months and &lt; 19 years&#xD;
&#xD;
          -  Patients diagnosed with Wiskott-Aldrich syndrome eligible for an allogeneic&#xD;
             transplantation and lacking a related HLA-matched donor&#xD;
&#xD;
          -  Lansky/Karnofsky score &gt; 40, WHO &gt; 4&#xD;
&#xD;
          -  Signed written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Dysfunction of liver (ALT/AST &gt; 5 times normal value, or bilirubin &gt; 3 times normal&#xD;
             value), or of renal function (creatinine clearance &lt; 30 ml / min)&#xD;
&#xD;
          -  Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive&#xD;
             heart failure or left ventricular ejection fraction &lt;40%)&#xD;
&#xD;
          -  Serious concurrent uncontrolled medical disorder&#xD;
&#xD;
          -  Lack of parents' informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>19 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexei Maschan, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dmitry Balashov</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dmitry Balashov, MD, PhD</last_name>
    <phone>+7(495)287-6570</phone>
    <phone_ext>6534</phone_ext>
    <email>bala8@yandex.ru</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Michael Maschan, Professor</last_name>
    <phone>+7(926)651-2145</phone>
    <email>mmaschan@yandex.ru</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology</name>
      <address>
        <city>Moscow</city>
        <zip>117997</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dmitry Balashov, MD, PhD</last_name>
      <phone>+7(495)287-6570</phone>
      <phone_ext>6534</phone_ext>
      <email>bala8@yandex.ru</email>
    </contact>
    <contact_backup>
      <last_name>Michael Maschan, Professor</last_name>
      <phone>+7(926)287-6570</phone>
      <email>mmaschan@yandex.ru</email>
    </contact_backup>
    <investigator>
      <last_name>Michael Maschan, Professor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alexandra Laberko, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Svetlana Kozlovskaya, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Elena Gutovskaya, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anna Shcherbina, Professor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>December 10, 2018</last_update_submitted>
  <last_update_submitted_qc>December 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Wiskott-Aldrich Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Plerixafor</mesh_term>
  </intervention_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/NCT03019809
org study id: WAS_PG 2016
nct id: NCT03019809
lead sponsor: 
has dmc: Yes
Treatment Study to assess of safety and efficiency of conditioning with Plerixafor and G-CSF
      as additional agents for prevention of graft failure after transplantation with TCR
      alpha/beta grafts depletion in patient with Wiskott-Aldrich syndrome.
Severe graft dysfunction, such as the degree of donor chimerism predominantly in the myeloid
      compartment is one of major problem in patients with Wiskott-Aldrich syndrome (WAS),
      especially after hematopoietic stem cell transplantation (HSCT) from alternative donor. It
      often leads to the development of severe thrombocytopenia or even transplants rejection. In
      this study the hypothesis is that the use of plerixafor and G-CSF as additional agents in
      conditioning regimen would offers advantages due to lowing risk of mixed chimerism after
      HSCT. This effect is based on the fact that simultaneous use of plerixafor with G-CSF is
      efficient in inducing stem cell release and opening of bone marrow (BM) niches. Moreover,
      stem cell release probably leads to liberation of host stem cells from the anti-apoptotic
      effects of the BM stroma for the more powerful effect of chemotherapy.

      In this study, the investigators use TCR alpha/beta grafts depletion of the grafts as basic
      technology for HSCT from haploidentical and unrelated donors approved in Institution.

      Thus, the purpose of this study is to evaluate the safety and efficiency of myeloablative
      conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure
      after transplantation with TCR alpha/beta grafts depletion in patients with Wiskott-Aldrich
      syndrome.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Event free survival (EFS)
time frame: 24 months
description: The EFS probability compared with historical control. We mean event as patient's death, second transplantation or persistence of severe thrombocytopenia
measure: Overall survival (OS)
time frame: 24 months
description: The OS probability compared with historical control.
measure: Percentage of patients with full/mixed donor chimerism
time frame: 12 months
description: Evaluation of the percentage of patients with the full/mixed donor chimerism (whole blood and CD3+ lineage). In addition, patients will be divided in accordance with % of donors cells: >95%; 50%-95%; 10%-49%; <10%. All data will be compared with historical control
measure: Transplant related mortality (TRM)
time frame: 24 months
description: The TRM probability compared with historical control.
measure: Severe thrombocytopenia (ST)
time frame: 24 months
description: The ST probability after HSCT compared with historical control
measure: Autoimmune complications (AC)
time frame: 24 months
description: The AC probability after HSCT compared with historical control
measure: Acute Graft Versus Host Diseases (aGVHD)
time frame: 12 months
description: Cumulative Incidence and severity of aGVHD
measure: Chronic Graft Versus Host Diseases (cGVHD)
time frame: 24 months
description: Cumulative Incidence and severity of cGVHD
measure: Plerixafor related complications (PRC)
time frame: 2 week
description: PRC: severity, features, incidence
arm group label: Plerixafor/G-CSF for HSCT conditioning
arm group type: Experimental
description: Myeloablative conditioning regimen with Plerixafor and G-CSF as addition agents before stem cell transplantation in WAS patients.
intervention type: Biological
intervention name: G-CSF for Conditioning before HSCT.
description: Mobilization of hematopoietic stem (HSC) into circulation
arm group label: Plerixafor/G-CSF for HSCT conditioning
intervention type: Biological
intervention name: Plerixafor for Conditioning before HSCT.
description: Directed inhibition of CXC chemokine receptor type 4 (CXCR4) for opening enough BM niches for adequate donor HSC engraftment.
arm group label: Plerixafor/G-CSF for HSCT conditioning
criteria: 
gender: All
minimum age: 1 Month
maximum age: 19 Years
healthy volunteers: No
last name: Alexei Maschan, Professor
role: Study Chair
affiliation: Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
last name: Dmitry Balashov
role: Principal Investigator
affiliation: Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
last name: Dmitry Balashov, MD, PhD
phone: +7(495)287-6570
phone ext: 6534
email: bala8@yandex.ru
last name: Michael Maschan, Professor
phone: +7(926)651-2145
email: mmaschan@yandex.ru
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Wiskott-Aldrich Syndrome
mesh term: Syndrome
mesh term: Plerixafor