<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/NCT04460963</url>
  </required_header>
  <id_info>
    <org_study_id>AML2220</org_study_id>
    <nct_id>NCT04460963</nct_id>
  </id_info>
  <brief_title>Role of Adrenomedullin in Leukemic Endosteal/Vascular Niches</brief_title>
  <official_title>Role of Adrenomedullin in Leukemic Endosteal/Vascular Niches</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gruppo Italiano Malattie EMatologiche dell'Adulto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gruppo Italiano Malattie EMatologiche dell'Adulto</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study will be divided into 5 phases:&#xD;
&#xD;
        1. Collection of bone marrow and peripheral blood (PB) samples from AML patients at&#xD;
           diagnosis;&#xD;
&#xD;
        2. Measurement of Midregional Proadrenomedullin (MR-proADM) plasma concentrations with an&#xD;
           Immunoluminometric Assay of newly diagnosed AML patients not affected by concomitant&#xD;
           cardiovascular disease or sepsis.&#xD;
&#xD;
        3. Analysis of exosomes and microvesicles derived from PB and bone marrow samples of AML&#xD;
           patients and culture media collected from AML samples stimulated with ADM and/or ADM&#xD;
           (22-52)&#xD;
&#xD;
        4. Study of adrenomedullin system in leukemic stem cells (CD44+/CD38-/CD31+/Lin-) in order&#xD;
           to define a correlated expression of ADM and ADM receptors (RAMPs, PAM) with adhesion&#xD;
           molecules (CD31, CD38, CD44s, CD44v6), cell cycle regulatory proteins (p21, p27) and&#xD;
           genes or molecules involved in the hematopoietic differentiation process (Cul5, CD11b,&#xD;
           CD11c, CD66, CD14, CD15, PML-RARα)&#xD;
&#xD;
        5. In vitro evaluation of ADM activity in the growth, maturation and trans-endothelial&#xD;
           migration of blasts and/or fusion of leukemic cells with endothelial cells. To do this,&#xD;
           leukemic cells will be alternatively cultured by using in vitro models of endosteal and&#xD;
           vascular niches.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 9, 2021</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of therapeutic potential of ADM inhibition on leukaemia stem cells</measure>
    <time_frame>at 1 year</time_frame>
    <description>Rate estimation of the in vitro arrest of leukemic blasts proliferation by ADM inhibition.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">72</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Biological evaluation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Adrenomedullin evaluation at diagnosis at first CR and 1 year of follow-up</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Adrenomedullin</intervention_name>
    <description>Adrenomedullin sample evaluation</description>
    <arm_group_label>Biological evaluation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with new diagnosis of primary or secondary AML.&#xD;
&#xD;
          2. Participant is willing and able to give signed written informed consent according to&#xD;
             ICH/EU/GCP and national local laws.&#xD;
&#xD;
          3. Male or Female, aged &gt;18 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients affected by concomitant cardiovascular disease , such as essential&#xD;
             hypertension (any grade), chronic renal failure (creatinine&gt;1.5 mg/dL), heart failure&#xD;
             (any NYHA class), and peripheral arterial occlusive diseases, or sepsis.&#xD;
&#xD;
          2. Patients affected by HIV, B or C hepatitis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Paola Fazi</last_name>
    <phone>0670390528</phone>
    <email>p.fazi@gimema.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Enrico Crea</last_name>
    <phone>0670390514</phone>
    <email>e.crea@gimema.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Policlinico S. Orsola-Malpighi - Uoc Ematologia</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antonio Curti</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>As Dell'Alto Adige, Ospedale Centrale Di Bolzano - Ematologia E Centro Trapianto Midollo Osseo</name>
      <address>
        <city>Bolzano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Federico Mosna</last_name>
      <phone>3404148772</phone>
      <email>federico.mosna@sabes.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>U.O. Oncoematologia IOV</name>
      <address>
        <city>Castelfranco Veneto</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michele Gottardi</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ente Ecclesiastico Casa Sollievo Della Sofferenza - Ematologia</name>
      <address>
        <city>San Giovanni Rotondo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicola Cascavilla</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Uo Ematologia - Azienda Ulss N.2 Marca Trevigiana</name>
      <address>
        <city>Treviso</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Filippo Gherlinzoni</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>November 24, 2022</last_update_submitted>
  <last_update_submitted_qc>November 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>adrenomedullin</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adrenomedullin</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/NCT04460963
org study id: AML2220
nct id: NCT04460963
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The present study will be divided into 5 phases:

        1. Collection of bone marrow and peripheral blood (PB) samples from AML patients at
           diagnosis;

        2. Measurement of Midregional Proadrenomedullin (MR-proADM) plasma concentrations with an
           Immunoluminometric Assay of newly diagnosed AML patients not affected by concomitant
           cardiovascular disease or sepsis.

        3. Analysis of exosomes and microvesicles derived from PB and bone marrow samples of AML
           patients and culture media collected from AML samples stimulated with ADM and/or ADM
           (22-52)

        4. Study of adrenomedullin system in leukemic stem cells (CD44+/CD38-/CD31+/Lin-) in order
           to define a correlated expression of ADM and ADM receptors (RAMPs, PAM) with adhesion
           molecules (CD31, CD38, CD44s, CD44v6), cell cycle regulatory proteins (p21, p27) and
           genes or molecules involved in the hematopoietic differentiation process (Cul5, CD11b,
           CD11c, CD66, CD14, CD15, PML-RARα)

        5. In vitro evaluation of ADM activity in the growth, maturation and trans-endothelial
           migration of blasts and/or fusion of leukemic cells with endothelial cells. To do this,
           leukemic cells will be alternatively cultured by using in vitro models of endosteal and
           vascular niches.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Evaluation of therapeutic potential of ADM inhibition on leukaemia stem cells
time frame: at 1 year
description: Rate estimation of the in vitro arrest of leukemic blasts proliferation by ADM inhibition.
arm group label: Biological evaluation
arm group type: Other
description: Adrenomedullin evaluation at diagnosis at first CR and 1 year of follow-up
intervention type: Other
intervention name: Adrenomedullin
description: Adrenomedullin sample evaluation
arm group label: Biological evaluation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paola Fazi
phone: 0670390528
email: p.fazi@gimema.it
last name: Enrico Crea
phone: 0670390514
email: e.crea@gimema.it
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Sponsor
mesh term: Adrenomedullin