<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/NCT03278145</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL16_0806</org_study_id>
    <nct_id>NCT03278145</nct_id>
  </id_info>
  <brief_title>Dependence Receptors and Leukemia</brief_title>
  <official_title>Dependence Receptors in Childhood Acute Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</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>
      Acute leukaemias (AL) are the first cause of cancer in children, with a majority of B acute&#xD;
      lymphoblastic leukemia (ALL). Some of the processes causing leukemogenesis are already&#xD;
      identified and well characterized in some AL subtypes such as translocation t (12; 21) of&#xD;
      good prognosis in ALL. However, translocations are not sufficient to explain all the&#xD;
      different processes of leukemogenesis, and other processes such as genetic / epigenetic&#xD;
      mutations leading to oncogene activation / inhibition of tumor suppressor genes are the&#xD;
      object research. Among the latter, mutations in tumor suppressor genes such as DCC (Deleted&#xD;
      in Colorectal Cancer) have recently been identified in solid cancers, such as in hemopathies.&#xD;
      This gene was subsequently characterized as encoding a &quot;dependence receptor&quot; specifically&#xD;
      binding to its Netrin-1 ligand.&#xD;
&#xD;
      Dependence receptors (RDs) are transmembrane receptors that cause cell death in the absence&#xD;
      of their ligand. RD decreases tumor progression and overexpression of their ligands is&#xD;
      observed in many cancers, such as B lymphomatous hemopathies in adults. Inhibition of the&#xD;
      RD-ligand interaction constitutes a new and original therapeutic target in oncology.&#xD;
&#xD;
      The aim of this study is to investigate whether RDs, in particular DCC, are expressed in&#xD;
      acute leukemia cells at the time of diagnosis or relapse in patients aged 1 to 18 years, and&#xD;
      then in these patients at the time of the remission balance. This research will be both&#xD;
      qualitative and quantitative.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 2017</start_date>
  <completion_date type="Anticipated">November 2019</completion_date>
  <primary_completion_date type="Anticipated">May 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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Detection of specific labeling of the DCC-dependent receptor on the surface of leukemic cells</measure>
    <time_frame>Maximum 4 months (sampling at the time of diagnosis / relapse and remission)</time_frame>
    <description>Primary endpoint: presence of specific labeling of the DCC-dependent receptor on the surface of leukemic cells that will be detectable in flow cytometry.&#xD;
This marking will be both qualitative (positive signal = presence of the receptor, absence of signal = absence of the receptor), and quantitative (percentage of expression of the receptor on the surface of the cells).</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Acute Leukemia</condition>
  <arm_group>
    <arm_group_label>Pediatric acute leukemia</arm_group_label>
    <description>Patients of the Institute of Hematology and Pediatric Oncology (IHOPe) with acute leukemia (LA) who came for initial diagnosis, relapse, or at the time of their remission .</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Genetic analyses</intervention_name>
    <description>Patients treated at the Institute of Hematology and Pediatric Oncology (IHOPe), a department of Prof. Y. Bertrand, for acute leukemia (LA) at the time of diagnosis initial, or relapse, after obtaining signed parental consent. The same patients will benefit from a new sample at the time of their remission balance. Analyses for this research will be made from bone marrow aspiration samples performed for diagnosis and treatment of these patients. The medical team will investigate whether RDs, in particular DCC, are expressed in acute leukemia cells at the time of diagnosis or relapse and then in these patients at the time of the remission balance. This research will be both qualitative and quantitative. Next, investigators will characterize the existence and then the level of expression of the ligand specific for DCC, Netrin-1, in these same leukemic cells, at the time of diagnosis / relapse and remission.</description>
    <arm_group_label>Pediatric acute leukemia</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Bone marrow aspiration sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The target population consists of patients aged 1 to 18 years treated at the Institute of&#xD;
        Hematology and Pediatric Oncology (IHOPe), a department of Prof. Y. Bertrand, for acute&#xD;
        leukemia (LA) at the time of diagnosis initial, or relapse, after obtaining signed parental&#xD;
        consent. The same patients will benefit from a new sample at the time of their remission&#xD;
        balance.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged between 1 and 18 years&#xD;
&#xD;
          -  taken care of at the Institute of Hematology and Pediatric Oncology (Service of&#xD;
             Professor Yves Bertrand, IHOPe)&#xD;
&#xD;
          -  for acute lymphoblastic or myeloblastic leukemia&#xD;
&#xD;
          -  initial diagnosis or relapse&#xD;
&#xD;
          -  who do not have a vital emergency criterion at the time of taking care (see exclusion&#xD;
             criteria)&#xD;
&#xD;
          -  affiliated to a social security scheme (100% assumed)&#xD;
&#xD;
          -  after signing the informed consent of the holders of parental authority&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  less than 1 year, or more than 18 years to diagnosis&#xD;
&#xD;
          -  with chronic leukemia&#xD;
&#xD;
          -  severe anemia at diagnosis (hemoglobin &lt;40g / l), or a state of shock whatever the&#xD;
             cause (infectious, cardiogenic, hypovolemic)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>Carine HALFON-DOMENECH, M.D, PhD</last_name>
    <phone>04 69 16 65 67</phone>
    <phone_ext>+33</phone_ext>
    <email>carine.halfon-domenech@chu-lyon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Patrick MEHLEN, MD</last_name>
    <phone>04-78-78-28-70</phone>
    <phone_ext>+33</phone_ext>
    <email>patrick.mehlen@lyon.unicancer.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institut d'Hématologie et d'Oncologie Pédiatrique</name>
      <address>
        <city>Lyon</city>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Carine HALFON-DOMENECH, M.D, PhD</last_name>
      <phone>04 69 16 65 67</phone>
      <phone_ext>+33</phone_ext>
      <email>carine.halfon-domenech@chu-lyon.fr</email>
    </contact>
    <contact_backup>
      <last_name>Patrick MEHLEN, MD</last_name>
      <phone>04-78-78-28-70</phone>
      <email>patrick.mehlen@lyon.unicancer.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Carine HALFON-DOMENECH, M.D, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>September 11, 2017</last_update_submitted>
  <last_update_submitted_qc>September 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 12, 2017</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>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</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/NCT03278145
org study id: 69HCL16_0806
nct id: NCT03278145
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Acute leukaemias (AL) are the first cause of cancer in children, with a majority of B acute
      lymphoblastic leukemia (ALL). Some of the processes causing leukemogenesis are already
      identified and well characterized in some AL subtypes such as translocation t (12; 21) of
      good prognosis in ALL. However, translocations are not sufficient to explain all the
      different processes of leukemogenesis, and other processes such as genetic / epigenetic
      mutations leading to oncogene activation / inhibition of tumor suppressor genes are the
      object research. Among the latter, mutations in tumor suppressor genes such as DCC (Deleted
      in Colorectal Cancer) have recently been identified in solid cancers, such as in hemopathies.
      This gene was subsequently characterized as encoding a "dependence receptor" specifically
      binding to its Netrin-1 ligand.

      Dependence receptors (RDs) are transmembrane receptors that cause cell death in the absence
      of their ligand. RD decreases tumor progression and overexpression of their ligands is
      observed in many cancers, such as B lymphomatous hemopathies in adults. Inhibition of the
      RD-ligand interaction constitutes a new and original therapeutic target in oncology.

      The aim of this study is to investigate whether RDs, in particular DCC, are expressed in
      acute leukemia cells at the time of diagnosis or relapse in patients aged 1 to 18 years, and
      then in these patients at the time of the remission balance. This research will be both
      qualitative and quantitative.
observational model: Cohort
time perspective: Prospective
measure: Detection of specific labeling of the DCC-dependent receptor on the surface of leukemic cells
time frame: Maximum 4 months (sampling at the time of diagnosis / relapse and remission)
description: Primary endpoint: presence of specific labeling of the DCC-dependent receptor on the surface of leukemic cells that will be detectable in flow cytometry.
This marking will be both qualitative (positive signal = presence of the receptor, absence of signal = absence of the receptor), and quantitative (percentage of expression of the receptor on the surface of the cells).
arm group label: Pediatric acute leukemia
description: Patients of the Institute of Hematology and Pediatric Oncology (IHOPe) with acute leukemia (LA) who came for initial diagnosis, relapse, or at the time of their remission .
intervention type: Genetic
intervention name: Genetic analyses
description: Patients treated at the Institute of Hematology and Pediatric Oncology (IHOPe), a department of Prof. Y. Bertrand, for acute leukemia (LA) at the time of diagnosis initial, or relapse, after obtaining signed parental consent. The same patients will benefit from a new sample at the time of their remission balance. Analyses for this research will be made from bone marrow aspiration samples performed for diagnosis and treatment of these patients. The medical team will investigate whether RDs, in particular DCC, are expressed in acute leukemia cells at the time of diagnosis or relapse and then in these patients at the time of the remission balance. This research will be both qualitative and quantitative. Next, investigators will characterize the existence and then the level of expression of the ligand specific for DCC, Netrin-1, in these same leukemic cells, at the time of diagnosis / relapse and remission.
arm group label: Pediatric acute leukemia
Bone marrow aspiration sample
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
last name: Carine HALFON-DOMENECH, M.D, PhD
phone: 04 69 16 65 67
phone ext: +33
email: carine.halfon-domenech@chu-lyon.fr
last name: Patrick MEHLEN, MD
phone: 04-78-78-28-70
phone ext: +33
email: patrick.mehlen@lyon.unicancer.fr
facility: 
contact: 
contact backup: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
sharing ipd: No