<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/NCT04437381</url>
  </required_header>
  <id_info>
    <org_study_id>APHP200137</org_study_id>
    <nct_id>NCT04437381</nct_id>
  </id_info>
  <brief_title>Molecular Targets for the Treatment of Histiocytosis</brief_title>
  <acronym>TARGET-HISTIO</acronym>
  <official_title>Molecular Targets for the Treatment of Histiocytosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Direction de l'Hospitalisation et de l'Organisation des Soins</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Versailles Saint-Quentin-en-Yvelines University, Paris-Saclay University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective: to develop technical and operating procedures for detection mutations&#xD;
      of histiocytosis during clinical practice of no-specialized molecular platforms, for&#xD;
      diagnosis and follow-up of the disease.&#xD;
&#xD;
      The secondary objectives: to describe therapeutic target mutations in histiocytosis patients,&#xD;
      and to develop the cellular tests to evaluate in vitro the sensibility of these mutations&#xD;
      drive to inhibitors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is ancillary of the French &quot;Gene Histio&quot; cohort (patients already included) and&#xD;
      &quot;HISTIO target 2020&quot; cohort (patients recruited since may 2020).&#xD;
&#xD;
      The data base of the French registry of histiocytoses is held by Dr J. Donadieu, and&#xD;
      localized in Trousseau hospital (APHP) 75012 Paris, France, where server and backup are kept.&#xD;
&#xD;
      5 teams contributes to the study with different role: Team 1 is responsible for histology&#xD;
      diagnosis, selection of histiocyte- rich areas, extraction of nucleic acids and detection of&#xD;
      the BRAF p.V600E mutations. This group is also responsible of the tissue and nucleic acids&#xD;
      biobank.&#xD;
&#xD;
      Team 2 is responsible for the collection of clinical data and tissue and blood samples of the&#xD;
      children. This group is also responsible of the clinical data base.&#xD;
&#xD;
      Team 3 is responsible for the collection of clinical data and tissue and blood samples of the&#xD;
      adult patients.&#xD;
&#xD;
      Team 4 is responsible for the development and validation of the new methods of detection of&#xD;
      genetic somatic alterations described in project, and will perform most of the molecular&#xD;
      analyses and interpretations.&#xD;
&#xD;
      Team 5 is responsible for regulatory requirements preparation and submissions and takes care&#xD;
      of replying to regulatory comments and amendments until getting approvals. The project&#xD;
      manager will also take care of the coordination of all activities related to the database&#xD;
      setting and utilization, liaising between researchers, doctors and operational team. Team 5&#xD;
      will be in charge of the data management of the database and will ensure collection tools,&#xD;
      integration and availability of data at appropriate quality. The data manager ensures that&#xD;
      data is collected, validated, complete, and consistent, to provide a high quality and&#xD;
      comprehensive database to the statistics team. Team 5 includes also a statistician who will&#xD;
      perform data analysis according to a detailed statistical analysis plan to be developed once&#xD;
      the project is approved.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 22, 2021</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">April 2025</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Molecular alterations in histiocytosis</measure>
    <time_frame>throughout of the study, an average of 3 years</time_frame>
    <description>Characterize the molecular alterations of nucleic acids in histiocytosis. Assess the frequency and type of drugable mutations in the different sub-types and localizations of histiocytosis Molecular alterations will be assessed by next analysis of DNA or RNA extracted from histiocytosis tissue or blood samples.</description>
  </primary_outcome>
  <enrollment type="Anticipated">1800</enrollment>
  <condition>Histiocytosis</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tissue and blood samples and derived nucleic acids.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Paediatric and adult patients with histologically proven histiocytosis, included in either&#xD;
        &quot;Gene Histio&quot; or &quot;HISTIO target 2020&quot; cohorts between 1997 and 2023.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically proven histiocytosis;&#xD;
&#xD;
          -  Informed consent form signed by patients (or parents/legal tutors of children) to&#xD;
             participate&quot;Gene Histio&quot; or &quot;HISTIO target 2020&quot;.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Patient refusal.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-François EMILE, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Pathology, Ambroise Paré hospital, APHP</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jean-François EMILE, MD, PhD</last_name>
    <phone>+33 1 49 09 57 25</phone>
    <email>jean-francois.emile@uvsq.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Biological research center, Ambroise Paré hospital, APHP</name>
      <address>
        <city>Boulogne Billancourt</city>
        <zip>92100</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Department of internal Medicine, Pitié-Salpétrière hospital, APHP</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Julien HAROCHE, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Department of Pediatrics, Trousseau hospital, APHP</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Jean DONADIEU, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>September 4, 2023</last_update_submitted>
  <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>histiocytosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Histiocytosis</mesh_term>
  </condition_browse>
  <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/NCT04437381
org study id: APHP200137
nct id: NCT04437381
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective: to develop technical and operating procedures for detection mutations
      of histiocytosis during clinical practice of no-specialized molecular platforms, for
      diagnosis and follow-up of the disease.

      The secondary objectives: to describe therapeutic target mutations in histiocytosis patients,
      and to develop the cellular tests to evaluate in vitro the sensibility of these mutations
      drive to inhibitors.
The study is ancillary of the French "Gene Histio" cohort (patients already included) and
      "HISTIO target 2020" cohort (patients recruited since may 2020).

      The data base of the French registry of histiocytoses is held by Dr J. Donadieu, and
      localized in Trousseau hospital (APHP) 75012 Paris, France, where server and backup are kept.

      5 teams contributes to the study with different role: Team 1 is responsible for histology
      diagnosis, selection of histiocyte- rich areas, extraction of nucleic acids and detection of
      the BRAF p.V600E mutations. This group is also responsible of the tissue and nucleic acids
      biobank.

      Team 2 is responsible for the collection of clinical data and tissue and blood samples of the
      children. This group is also responsible of the clinical data base.

      Team 3 is responsible for the collection of clinical data and tissue and blood samples of the
      adult patients.

      Team 4 is responsible for the development and validation of the new methods of detection of
      genetic somatic alterations described in project, and will perform most of the molecular
      analyses and interpretations.

      Team 5 is responsible for regulatory requirements preparation and submissions and takes care
      of replying to regulatory comments and amendments until getting approvals. The project
      manager will also take care of the coordination of all activities related to the database
      setting and utilization, liaising between researchers, doctors and operational team. Team 5
      will be in charge of the data management of the database and will ensure collection tools,
      integration and availability of data at appropriate quality. The data manager ensures that
      data is collected, validated, complete, and consistent, to provide a high quality and
      comprehensive database to the statistics team. Team 5 includes also a statistician who will
      perform data analysis according to a detailed statistical analysis plan to be developed once
      the project is approved.
observational model: Cohort
time perspective: Prospective
measure: Molecular alterations in histiocytosis
time frame: throughout of the study, an average of 3 years
description: Characterize the molecular alterations of nucleic acids in histiocytosis. Assess the frequency and type of drugable mutations in the different sub-types and localizations of histiocytosis Molecular alterations will be assessed by next analysis of DNA or RNA extracted from histiocytosis tissue or blood samples.
Tissue and blood samples and derived nucleic acids.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Jean-François EMILE, MD, PhD
role: Principal Investigator
affiliation: Department of Pathology, Ambroise Paré hospital, APHP
last name: Jean-François EMILE, MD, PhD
phone: +33 1 49 09 57 25
email: jean-francois.emile@uvsq.fr
facility: 
status: Recruiting
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
country: France
responsible party type: Sponsor
mesh term: Histiocytosis
sharing ipd: No