<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/NCT03789981</url>
  </required_header>
  <id_info>
    <org_study_id>IRSTB082</org_study_id>
    <nct_id>NCT03789981</nct_id>
  </id_info>
  <brief_title>Exploring Disease Immunogenicity and the Immunological Effects of Hypomethylating Agents in Acute Myeloid Leukemia</brief_title>
  <acronym>Immune-AML</acronym>
  <official_title>Exploring Disease Immunogenicity and the Immunological Effects of Hypomethylating Agents in Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori</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>
      This is a multicenter, prospective, translational study, to evaluate the immunogenic profile&#xD;
      of AML cases according to immune checkpoint molecule expression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, prospective, translational study. Pharmacological treatments will not&#xD;
      be object of the present study. Patients will follow the prescribed therapeutic indications&#xD;
      according to regular clinical practice. Biological samples and clinical data will be&#xD;
      collected at fixed timepoints.&#xD;
&#xD;
      Aim of the study is to evaluate the immunogenic profile of AML cases according to immune&#xD;
      checkpoint molecule expression.&#xD;
&#xD;
      A total of 75 AML patients affected by primary or secondary AML, at diagnosis ( 45 patients)&#xD;
      or relapse (30 patients) will be enrolled in the protocol (18 months for patient enrolment).&#xD;
      Blood,BM and saliva samples will be collected from each patients; for patients enrolled at&#xD;
      diagnosis, samples will be collected before and after treatment with hypomethylating agents.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 19, 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</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>Evaluation of the Immunogenic profile of primary or secondary AML patients in according to the variations in expression of molecules involved in immune checkpoint</measure>
    <time_frame>up to 30 months</time_frame>
    <description>The immunogenic profile of AML cases obtained by NeoAgprediction will be related with established biological and clinical parameters (including karyotype, percentage of blasts, clinical outcome) performing RNA sequencing (RNAseq) and whole exome sequencing (WES) analysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Investigation of the relationship between leukemia immunogenicity and immune checkpoint activation</measure>
    <time_frame>up to 30 months</time_frame>
    <description>the relationship between leukemia immunogenicity and immune checkpoint activation through transcriptome analysis of downstream pathways by flow cytometric analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigation of the activation of immune checkpoint molecules</measure>
    <time_frame>up to 30 months</time_frame>
    <description>Investigation of the activation of immune checkpoint molecules under the selective pressure of hypomethylating agents treatment by gene expression profilling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The investigation of the association of the immune checkpoint status with clinical outcomes</measure>
    <time_frame>up to 30 months</time_frame>
    <description>Investigation of the association of the immune checkpoint status with clinical outcomes (OS, PFS) estimated according to Kaplan-Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The investigation of the association of the immunogenic profile with clinical outcomes</measure>
    <time_frame>up to 30 months</time_frame>
    <description>Investigation of the association of the immunogenic profile with clinical outcomes (OS, PFS) estimated according to Kaplan-Meier.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">75</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>At diagnosis</arm_group_label>
    <description>Immunogenic profile in patients affected by primary or secondary AML at diagnosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>At relapse</arm_group_label>
    <description>Immunogenic profile in patients affected by primary or secondary AML at relapse</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Immunogenic profile</intervention_name>
    <description>RNA sequencing (RNAseq), Whole exome sequencing (WES), NeoAntigens (NeoAg), Immune checkpoints analysis, Gene expression profiling</description>
    <arm_group_label>At diagnosis</arm_group_label>
    <arm_group_label>At relapse</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Bone marrow (BM) and peripheral blood (PB) and saliva.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        AML patients affected by primary or secondary AML, at diagnosis or relapse&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with new diagnosis of primary or secondary AML candidate to first line&#xD;
             treatment with hypomethylating agents (specific for Cohort 1) Patients with primary or&#xD;
             secondary AML who relapse after/during first line treatment with hypomethylating&#xD;
             agents (specific for Cohort 2)&#xD;
&#xD;
             for each cohort:&#xD;
&#xD;
          2. Participant is willing and able to give informed consent for participation in the&#xD;
             study&#xD;
&#xD;
          3. Male or Female, aged &gt;18 years&#xD;
&#xD;
          4. Availability of clinical data&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt; 18 years&#xD;
&#xD;
          2. AML M3 subtype according to FAB classification&#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_official>
    <last_name>Giovanni Martinelli</last_name>
    <role>Study Chair</role>
    <affiliation>Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Oriana Nanni</last_name>
    <phone>+390543739266</phone>
    <email>oriana.nanni@irst.emr.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>AO Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Erika Brolenghi, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)</name>
      <address>
        <city>Meldola</city>
        <state>FC</state>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giovanni Martinelli, MD</last_name>
      <phone>+390543739100</phone>
      <email>giovanni.martinelli@irst.emr.it</email>
    </contact>
    <investigator>
      <last_name>Giovanni Martinelli, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Giorgia Simonetti, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marianna Norata, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Martina Ghetti, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>IRCCS Casa sollievo sofferenza</name>
      <address>
        <city>San Giovanni Rotondo</city>
        <state>Foggia</state>
        <zip>71013</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicola Cascavilla, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>IRCCS AOU S. Martino Genova</name>
      <address>
        <city>Genova</city>
        <state>GE</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roberto Massimo Lemoli, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale G. Da Saliceto</name>
      <address>
        <city>Piacenza</city>
        <state>PC</state>
        <zip>29121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniele Vallisa</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Irccs Crob</name>
      <address>
        <city>Rionero in Vulture</city>
        <state>PZ</state>
        <zip>85028</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pellegrino Musto, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Osp. S. Maria delle Croci</name>
      <address>
        <city>Ravenna</city>
        <state>RA</state>
        <zip>48121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michela Rondoni, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale degli Infermi</name>
      <address>
        <city>Rimini</city>
        <state>RN</state>
        <zip>47923</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Maria Mianulli, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AOU Senese</name>
      <address>
        <city>Siena</city>
        <state>SI</state>
        <zip>53100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Monica Bocchia, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Università di Torino</name>
      <address>
        <city>Orbassano</city>
        <state>TO</state>
        <zip>10043</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Daniela Cilloni, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AO Ordine Mauriziano di Torino</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <zip>10128</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alessandro Cignetti, DR</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda ULSS2 Marca Trevigiana</name>
      <address>
        <city>Treviso</city>
        <state>TV</state>
        <zip>31100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michele Gottardi, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AOU Maggiore della Carità</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Monia Lunghi</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AOU di Udine</name>
      <address>
        <city>Udine</city>
        <zip>33010</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Candoni, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>November 8, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 31, 2018</study_first_posted>
  <last_update_submitted>February 25, 2021</last_update_submitted>
  <last_update_submitted_qc>February 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AML</keyword>
  <keyword>Acute Myeloid Leukemia</keyword>
  <keyword>Immunogenic profile</keyword>
  <keyword>transcriptome analysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_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/NCT03789981
org study id: IRSTB082
nct id: NCT03789981
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicenter, prospective, translational study, to evaluate the immunogenic profile
      of AML cases according to immune checkpoint molecule expression.
This is a multicenter, prospective, translational study. Pharmacological treatments will not
      be object of the present study. Patients will follow the prescribed therapeutic indications
      according to regular clinical practice. Biological samples and clinical data will be
      collected at fixed timepoints.

      Aim of the study is to evaluate the immunogenic profile of AML cases according to immune
      checkpoint molecule expression.

      A total of 75 AML patients affected by primary or secondary AML, at diagnosis ( 45 patients)
      or relapse (30 patients) will be enrolled in the protocol (18 months for patient enrolment).
      Blood,BM and saliva samples will be collected from each patients; for patients enrolled at
      diagnosis, samples will be collected before and after treatment with hypomethylating agents.
observational model: Cohort
time perspective: Prospective
measure: Evaluation of the Immunogenic profile of primary or secondary AML patients in according to the variations in expression of molecules involved in immune checkpoint
time frame: up to 30 months
description: The immunogenic profile of AML cases obtained by NeoAgprediction will be related with established biological and clinical parameters (including karyotype, percentage of blasts, clinical outcome) performing RNA sequencing (RNAseq) and whole exome sequencing (WES) analysis
measure: Investigation of the relationship between leukemia immunogenicity and immune checkpoint activation
time frame: up to 30 months
description: the relationship between leukemia immunogenicity and immune checkpoint activation through transcriptome analysis of downstream pathways by flow cytometric analysis
measure: Investigation of the activation of immune checkpoint molecules
time frame: up to 30 months
description: Investigation of the activation of immune checkpoint molecules under the selective pressure of hypomethylating agents treatment by gene expression profilling
measure: The investigation of the association of the immune checkpoint status with clinical outcomes
time frame: up to 30 months
description: Investigation of the association of the immune checkpoint status with clinical outcomes (OS, PFS) estimated according to Kaplan-Meier.
measure: The investigation of the association of the immunogenic profile with clinical outcomes
time frame: up to 30 months
description: Investigation of the association of the immunogenic profile with clinical outcomes (OS, PFS) estimated according to Kaplan-Meier.
arm group label: At diagnosis
description: Immunogenic profile in patients affected by primary or secondary AML at diagnosis
arm group label: At relapse
description: Immunogenic profile in patients affected by primary or secondary AML at relapse
intervention type: Genetic
intervention name: Immunogenic profile
description: RNA sequencing (RNAseq), Whole exome sequencing (WES), NeoAntigens (NeoAg), Immune checkpoints analysis, Gene expression profiling
arm group label: At diagnosis
arm group label: At relapse
Bone marrow (BM) and peripheral blood (PB) and saliva.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Giovanni Martinelli
role: Study Chair
affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
last name: Oriana Nanni
phone: +390543739266
email: oriana.nanni@irst.emr.it
facility: 
status: Not yet recruiting
contact: 
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status: Recruiting
contact: 
investigator: 
investigator: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Not yet recruiting
contact: 
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status: Not yet recruiting
contact: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
contact: 
country: Italy
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute