<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/NCT03294824</url>
  </required_header>
  <id_info>
    <org_study_id>P111107</org_study_id>
    <secondary_id>IDRCB</secondary_id>
    <nct_id>NCT03294824</nct_id>
  </id_info>
  <brief_title>Non Randomized Comparative Study With Control</brief_title>
  <acronym>Allo-NK-CMV</acronym>
  <official_title>Study of Natural Killer Immunity During Infections With CMV or AdV After Allogeneic Hematopoietic Stem Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      NK cells are lymphocytes who play a role in the control of viral infections , tumor and fœtal&#xD;
      tolerance. They belong to innate immune cells but they have a link with adaptative immunity.&#xD;
      Indeed, after some viral infections such as CMV, Chikungunya, B hepatitis etc, a subset of&#xD;
      NKG2C+ NK cells expands and can transfer, in murine models, a &quot; memory &quot; that can better&#xD;
      control CMV infections. CMV reactivation is a major cause of morbidity and mortality after&#xD;
      allogeneic hematopoietic ste cell transplantation in humans. The aim of this prospective&#xD;
      study is to evaluate the role of NK cells, in particular NKG2C+ NK cells in the control of&#xD;
      CMV but also Adenovirus after allo HSCT. Peripheral NK cells from 30 and 10 patients who&#xD;
      reactivated respectively CMV and AdV are prospectively studied (extensive phenotyping and&#xD;
      functional studies before and after administration of anti viral drugs) and compared with 30&#xD;
      allotransplanted patients who didn't reactivate CMV in a pair analysis, and 30 healthy donors&#xD;
      serologically + for CMV.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For both groups: 28ml of peripheral blood samples are collected at different points. Group 1&#xD;
      : before and after anti viral treatment . Control group 2: one point after allo-HSCT; Control&#xD;
      group 3: 1 point before transplant. Phenotypical study of NK cells: activating and inhibitory&#xD;
      receptors, activation and differentiation's markers. Phenotypical studies of the ligands on&#xD;
      infected cells. Genotypic study of KIR receptors (Kirotype); functional studies:&#xD;
      polyfunctionality essay (flow cytometry): degranulation CD107a, IFNg, TNFa production).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 27, 2013</start_date>
  <completion_date type="Anticipated">June 2018</completion_date>
  <primary_completion_date type="Anticipated">June 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Nk cells phenotype (activation, differentiation, memory NK cell) and function (cytoxicity and cytokines production) measured by flow cytometry</measure>
    <time_frame>Change from &quot;before antiviral treatment&quot;, &quot; half treatment&quot; (1 week or 2 week after the beginning of the treatment), 1 month &quot;post treatment&quot; and 3 month &quot;post treatment&quot;</time_frame>
    <description>CD3-CD56+ NK cells will be analyzed by Flow cytometry with an appropriate monoclonal antibodies (mAb) cocktail: anti-CD3 ,CD56, CD16, CD159a/NKG2A , CD85J; HLA-DR ; CD62L , CD161; KIR2DL1 and KIR3DL1, and KIR2DL2/KIR2DL3.&#xD;
The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic markers and will be compared with healthy donors.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>NK cells cytoxicity and cytokines production when incubated with standard HLA class I negative K562 target cells</measure>
    <time_frame>Change from &quot;before antiviral treatment&quot;, &quot; half treatment&quot; (1 week or 2 week after the beginning of the treatment), 1 month &quot;post treatment&quot; and 3 month &quot;post treatment&quot;</time_frame>
    <description>Polyfunctional assay will test the capacity of NK cells degranulation and production of cytokines when incubated with standard HLA class I negative K562 target cells in the presence of anti-CD107a ,IFN-g, or TNF-a mAb.&#xD;
The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and will be compared with healthy donors.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of CMV and AdV infection compared with healthy donors</measure>
    <time_frame>Change from &quot;before antiviral treatment&quot;, &quot; half treatment&quot; (1 week or 2 week after the beginning of the treatment), 1 month &quot;post treatment&quot; and 3 month &quot;post treatment&quot;</time_frame>
    <description>The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and functional markers and will be compared with healthy donors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In vitro Nk cells ligands analyzes on infected cells by CMV</measure>
    <time_frame>approximately 18 months after Study Completion Date (last participant's last visit)</time_frame>
    <description>Monocyte are differentiated in macrophage cells and infected by the CMV strain TB40/E. Nk cell ligands will be analyzed on infected cells. NK cells from infected patients post allogenic transplantation will be tested against in vitro infected cells.&#xD;
Being a model in vitro, it is not possible to determine in advance which ligands will be identified.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Allogeneic Hematopoietic Stem Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>patients who reactivate CMV or AdV after allogeneic HSCT</arm_group_label>
    <description>allotransplanted patients who reactivated respectively CMV (n=30) and AdV (n=10)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group: allogeneic HSC transplanted patients</arm_group_label>
    <description>allotransplanted patients who didn't reactivate CMV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy donors group</arm_group_label>
    <description>healthy donors serologically + for CMV</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood sample</intervention_name>
    <description>peripheral blood samples are collected</description>
    <arm_group_label>Control group: allogeneic HSC transplanted patients</arm_group_label>
    <arm_group_label>Healthy donors group</arm_group_label>
    <arm_group_label>patients who reactivate CMV or AdV after allogeneic HSCT</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Allogeneic HSCT for malignant or non malignant hematological disease in adult patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. patients who reactivate CMV or AdV after allogeneic HSCT ;&#xD;
&#xD;
               -  Age&gt;18 years; indication for a antiviral treatment:&#xD;
&#xD;
               -  at least 1 PCR CMV&gt;1000 copies/ml or 1 PCR ADV&gt;1000 copies/ml or at least 2 ADV&#xD;
                  PCR positive - sites (stools, throat, urines);&#xD;
&#xD;
               -  signed informed consent;&#xD;
&#xD;
          2. Control group: allogeneic HSC transplanted patients;&#xD;
&#xD;
               -  Age&gt;18 years; no CMV or AdV reactivation ;&#xD;
&#xD;
               -  signed informed consent;&#xD;
&#xD;
          3. Healthy donors group: HSC donor;&#xD;
&#xD;
               -  Age&gt;18 years;&#xD;
&#xD;
               -  signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        none&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephanie Nguyen Quoc, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Stephanie Nguyen Quoc, Doctor</last_name>
    <phone>33142162823</phone>
    <email>stephanie.nguyen-quoc@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laetitia Souchet, Doctor</last_name>
    <phone>33142162823</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital Pitié Salpêtriere</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>February 15, 2016</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <last_update_submitted>May 25, 2018</last_update_submitted>
  <last_update_submitted_qc>May 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NK cells</keyword>
  <keyword>Cytomegalovirus</keyword>
  <keyword>adenovirus</keyword>
  <keyword>Allogeneic transplantation</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03294824
org study id: P111107
secondary id: IDRCB
nct id: NCT03294824
lead sponsor: 
has dmc: No
NK cells are lymphocytes who play a role in the control of viral infections , tumor and fœtal
      tolerance. They belong to innate immune cells but they have a link with adaptative immunity.
      Indeed, after some viral infections such as CMV, Chikungunya, B hepatitis etc, a subset of
      NKG2C+ NK cells expands and can transfer, in murine models, a " memory " that can better
      control CMV infections. CMV reactivation is a major cause of morbidity and mortality after
      allogeneic hematopoietic ste cell transplantation in humans. The aim of this prospective
      study is to evaluate the role of NK cells, in particular NKG2C+ NK cells in the control of
      CMV but also Adenovirus after allo HSCT. Peripheral NK cells from 30 and 10 patients who
      reactivated respectively CMV and AdV are prospectively studied (extensive phenotyping and
      functional studies before and after administration of anti viral drugs) and compared with 30
      allotransplanted patients who didn't reactivate CMV in a pair analysis, and 30 healthy donors
      serologically + for CMV.
For both groups: 28ml of peripheral blood samples are collected at different points. Group 1
      : before and after anti viral treatment . Control group 2: one point after allo-HSCT; Control
      group 3: 1 point before transplant. Phenotypical study of NK cells: activating and inhibitory
      receptors, activation and differentiation's markers. Phenotypical studies of the ligands on
      infected cells. Genotypic study of KIR receptors (Kirotype); functional studies:
      polyfunctionality essay (flow cytometry): degranulation CD107a, IFNg, TNFa production).
observational model: Case-Control
time perspective: Prospective
measure: Nk cells phenotype (activation, differentiation, memory NK cell) and function (cytoxicity and cytokines production) measured by flow cytometry
time frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
description: CD3-CD56+ NK cells will be analyzed by Flow cytometry with an appropriate monoclonal antibodies (mAb) cocktail: anti-CD3 ,CD56, CD16, CD159a/NKG2A , CD85J; HLA-DR ; CD62L , CD161; KIR2DL1 and KIR3DL1, and KIR2DL2/KIR2DL3.
The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic markers and will be compared with healthy donors.
measure: NK cells cytoxicity and cytokines production when incubated with standard HLA class I negative K562 target cells
time frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
description: Polyfunctional assay will test the capacity of NK cells degranulation and production of cytokines when incubated with standard HLA class I negative K562 target cells in the presence of anti-CD107a ,IFN-g, or TNF-a mAb.
The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and will be compared with healthy donors.
measure: Effect of CMV and AdV infection compared with healthy donors
time frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
description: The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and functional markers and will be compared with healthy donors.
measure: In vitro Nk cells ligands analyzes on infected cells by CMV
time frame: approximately 18 months after Study Completion Date (last participant's last visit)
description: Monocyte are differentiated in macrophage cells and infected by the CMV strain TB40/E. Nk cell ligands will be analyzed on infected cells. NK cells from infected patients post allogenic transplantation will be tested against in vitro infected cells.
Being a model in vitro, it is not possible to determine in advance which ligands will be identified.
arm group label: patients who reactivate CMV or AdV after allogeneic HSCT
description: allotransplanted patients who reactivated respectively CMV (n=30) and AdV (n=10)
arm group label: Control group: allogeneic HSC transplanted patients
description: allotransplanted patients who didn't reactivate CMV
arm group label: Healthy donors group
description: healthy donors serologically + for CMV
intervention type: Other
intervention name: blood sample
description: peripheral blood samples are collected
arm group label: Control group: allogeneic HSC transplanted patients
arm group label: Healthy donors group
arm group label: patients who reactivate CMV or AdV after allogeneic HSCT
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Stephanie Nguyen Quoc, Doctor
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Stephanie Nguyen Quoc, Doctor
phone: 33142162823
email: stephanie.nguyen-quoc@aphp.fr
last name: Laetitia Souchet, Doctor
phone: 33142162823
facility: 
status: Recruiting
country: France
responsible party type: Sponsor
sharing ipd: No