<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/NCT04446741</url>
  </required_header>
  <id_info>
    <org_study_id>PCR-LMA</org_study_id>
    <nct_id>NCT04446741</nct_id>
  </id_info>
  <brief_title>Molecular Diagnostic Platform for AML</brief_title>
  <official_title>Developing a Molecular Diagnostic Platform for Personalized Medicine for Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PETHEMA Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PETHEMA Foundation</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>
      This will be a translational study without any therapeutic intervention, for the purpose of&#xD;
      analyzing the diagnostic and molecular results / characterization of adult patients with AML,&#xD;
      regardless of the treatment they receive. Newly diagnosed or relapsed/resistant AML patients&#xD;
      will be included.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a multicenter, translational study without any therapeutic intervention. It will&#xD;
      be conducted at 7 central laboratories (Hospital Universitari i Politècnic La Fe, Hospital&#xD;
      Universitario de Salamanca, Hospital 12 de Octubre, Hospital Universitario Virgen del Rocío,&#xD;
      Hospital Dr. Negrín de Las Palmas de Gran Canaria, Hospital Reina Sofía de Córdoba and&#xD;
      Clínica Universidad de Navarra) belonging to the Spanish PETHEMA Group. The laboratories will&#xD;
      receive and process bone marrow and peripheral blood samples of patients with AML at the time&#xD;
      of the initial diagnosis or at relapse or resistance (first or subsequent&#xD;
      relapse/resistance). The demographic data and clinical characteristics of the patients and of&#xD;
      the AML, morphological and molecular response will be collected in case report forms (CRFs).&#xD;
      Since the aim of this study is the molecular diagnosis of AML, all patients with AML will be&#xD;
      included, regardless of the treatment (or no treatment at all) they receive.&#xD;
&#xD;
      The physicians will receive the report about the molecular diagnosis for FLT3, NPM1, CBF and&#xD;
      PML/RARa quickly (&lt;48-96 hours), in order to provide them with knowledge of the mutational&#xD;
      status, that may cause changes to be made during the initial management of the disease.&#xD;
&#xD;
      The aim of this project is to set up this rapid screening and diagnostic platform for AML by&#xD;
      having specimens sent to 7 centralized reference laboratories across the country, where the&#xD;
      molecular characteristics of leukemic cells will be analyzed by qRT-PCR and NGS technologies&#xD;
      with high quality standards. This platform will provide homogeneous criteria for assessing&#xD;
      the biological characteristics of the different entities that make up the disease.&#xD;
&#xD;
      It is expected that samples of marrow and/or blood of 700 patients with AML will be analyzed&#xD;
      per year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Anticipated">October 2022</completion_date>
  <primary_completion_date type="Anticipated">October 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of FLT3, NPM1 and CEBPa mutations</measure>
    <time_frame>Baseline</time_frame>
    <description>Frequency of each of the standard screening panel molecular alterations studied in the AML patients (FLT3, NPM1 and CEBPa), both in newly diagnosed and relapsed/resistant disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of mutations detected by Next Generation Sequency (NGS)</measure>
    <time_frame>Baseline</time_frame>
    <description>Frequency of mutations detected by NGS PCR (23 genes: FLT3, NPM1, DNMT3A, IDH2, IDH1, TET2, RUNX1, TP53, NRAS, WT1, PTPN11, KIT, U2AF1, KRAS, SMC1A, SMC3, PHF6, STAG2, RAD21, FAM5C, EZH2 and HNRNPK; if new genes are described,the panel can be extended) in every sample (diagnosis, relapse)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of mutations detected by conventional PCR (FLT3, NPM1 and CEBPa) in every sample (diagnosis, relapse)</measure>
    <time_frame>Baseline</time_frame>
    <description>Frequency of each of the standard screening panel molecular alterations studied by the conventional PCR in the AML patients (FLT3, NPM1 and CEBPa), both in newly diagnosed and relapsed/resistant disease.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">2000</enrollment>
  <condition>Acute Myeloid Leukemia (AML)</condition>
  <arm_group>
    <arm_group_label>Acute Myeloid Leukemia (AML)</arm_group_label>
    <description>Newly diagnosed or relapsed/resistant AML</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Bone marrow and peripheral blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients aged ≥18 years with a diagnosis of AML (new, relapse or refractory).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have voluntarily given informed consent for the sending and processing of biological&#xD;
             specimens, as well as for the analysis and reporting of the results on the mutation&#xD;
             status of their AML.&#xD;
&#xD;
          -  Age greater than or equal to 18 years.&#xD;
&#xD;
          -  Morphological diagnosis of AML or acute leukemia of ambiguous lineage according to WHO&#xD;
             criteria at diagnosis, relapse or resistance.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability of the patient or his/her legal representative to understand and voluntarily&#xD;
             sign the informed consent form&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pau Montesinos</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario La Fe</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Olga Garcia</last_name>
    <phone>+34 609 128 678</phone>
    <email>publi@fundacionpethema.es</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital Universitario Reina Sofía</name>
      <address>
        <city>Córdoba</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joaquín Sánchez</last_name>
    </contact>
    <investigator>
      <last_name>Joaquín Sánchez</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Gran Canaria Dr. Negrín</name>
      <address>
        <city>Las Palmas De Gran Canaria</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maite Gómez Casares</last_name>
    </contact>
    <investigator>
      <last_name>Maite Gómez Casares</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Doce de Octubre</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rosa Ayala</last_name>
    </contact>
    <investigator>
      <last_name>Rosa Ayala</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clínica Universidad de Navarra</name>
      <address>
        <city>Pamplona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>María José Calasanz</last_name>
    </contact>
    <investigator>
      <last_name>María José Calasanz</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carmen Chillon</last_name>
    </contact>
    <investigator>
      <last_name>Carmen Chillon</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>José Antonio Pérez Simón</last_name>
    </contact>
    <investigator>
      <last_name>José Antonio Pérez Simón</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Fe</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eva Barragan</last_name>
    </contact>
    <investigator>
      <last_name>Eva Barragán</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.</citation>
    <PMID>19880497</PMID>
  </reference>
  <reference>
    <citation>Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485.</citation>
    <PMID>18987736</PMID>
  </reference>
  <reference>
    <citation>Miller CA, Wilson RK, Ley TJ. Genomic landscapes and clonality of de novo AML. N Engl J Med. 2013 Oct 10;369(15):1473. doi: 10.1056/NEJMc1308782. No abstract available.</citation>
    <PMID>24106950</PMID>
  </reference>
  <reference>
    <citation>Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, Tidefelt U, Wahlin A, Hoglund M. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009 Apr 30;113(18):4179-87. doi: 10.1182/blood-2008-07-172007. Epub 2008 Nov 13.</citation>
    <PMID>19008455</PMID>
  </reference>
  <reference>
    <citation>Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. doi: 10.1182/blood-2016-08-733196. Epub 2016 Nov 28.</citation>
    <PMID>27895058</PMID>
  </reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>September 3, 2021</last_update_submitted>
  <last_update_submitted_qc>September 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AML</keyword>
  <keyword>Adult</keyword>
  <keyword>Molecular</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/NCT04446741
org study id: PCR-LMA
nct id: NCT04446741
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This will be a translational study without any therapeutic intervention, for the purpose of
      analyzing the diagnostic and molecular results / characterization of adult patients with AML,
      regardless of the treatment they receive. Newly diagnosed or relapsed/resistant AML patients
      will be included.
This will be a multicenter, translational study without any therapeutic intervention. It will
      be conducted at 7 central laboratories (Hospital Universitari i Politècnic La Fe, Hospital
      Universitario de Salamanca, Hospital 12 de Octubre, Hospital Universitario Virgen del Rocío,
      Hospital Dr. Negrín de Las Palmas de Gran Canaria, Hospital Reina Sofía de Córdoba and
      Clínica Universidad de Navarra) belonging to the Spanish PETHEMA Group. The laboratories will
      receive and process bone marrow and peripheral blood samples of patients with AML at the time
      of the initial diagnosis or at relapse or resistance (first or subsequent
      relapse/resistance). The demographic data and clinical characteristics of the patients and of
      the AML, morphological and molecular response will be collected in case report forms (CRFs).
      Since the aim of this study is the molecular diagnosis of AML, all patients with AML will be
      included, regardless of the treatment (or no treatment at all) they receive.

      The physicians will receive the report about the molecular diagnosis for FLT3, NPM1, CBF and
      PML/RARa quickly (<48-96 hours), in order to provide them with knowledge of the mutational
      status, that may cause changes to be made during the initial management of the disease.

      The aim of this project is to set up this rapid screening and diagnostic platform for AML by
      having specimens sent to 7 centralized reference laboratories across the country, where the
      molecular characteristics of leukemic cells will be analyzed by qRT-PCR and NGS technologies
      with high quality standards. This platform will provide homogeneous criteria for assessing
      the biological characteristics of the different entities that make up the disease.

      It is expected that samples of marrow and/or blood of 700 patients with AML will be analyzed
      per year.
observational model: Case-Only
time perspective: Prospective
measure: Frequency of FLT3, NPM1 and CEBPa mutations
time frame: Baseline
description: Frequency of each of the standard screening panel molecular alterations studied in the AML patients (FLT3, NPM1 and CEBPa), both in newly diagnosed and relapsed/resistant disease.
measure: Frequency of mutations detected by Next Generation Sequency (NGS)
time frame: Baseline
description: Frequency of mutations detected by NGS PCR (23 genes: FLT3, NPM1, DNMT3A, IDH2, IDH1, TET2, RUNX1, TP53, NRAS, WT1, PTPN11, KIT, U2AF1, KRAS, SMC1A, SMC3, PHF6, STAG2, RAD21, FAM5C, EZH2 and HNRNPK; if new genes are described,the panel can be extended) in every sample (diagnosis, relapse)
measure: Frequency of mutations detected by conventional PCR (FLT3, NPM1 and CEBPa) in every sample (diagnosis, relapse)
time frame: Baseline
description: Frequency of each of the standard screening panel molecular alterations studied by the conventional PCR in the AML patients (FLT3, NPM1 and CEBPa), both in newly diagnosed and relapsed/resistant disease.
arm group label: Acute Myeloid Leukemia (AML)
description: Newly diagnosed or relapsed/resistant AML
Bone marrow and peripheral blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Pau Montesinos
role: Principal Investigator
affiliation: Hospital Universitario La Fe
last name: Olga Garcia
phone: +34 609 128 678
email: publi@fundacionpethema.es
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Spain
citation: Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.
PMID: 19880497
citation: Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485.
PMID: 18987736
citation: Miller CA, Wilson RK, Ley TJ. Genomic landscapes and clonality of de novo AML. N Engl J Med. 2013 Oct 10;369(15):1473. doi: 10.1056/NEJMc1308782. No abstract available.
PMID: 24106950
citation: Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, Tidefelt U, Wahlin A, Hoglund M. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009 Apr 30;113(18):4179-87. doi: 10.1182/blood-2008-07-172007. Epub 2008 Nov 13.
PMID: 19008455
citation: Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. doi: 10.1182/blood-2016-08-733196. Epub 2016 Nov 28.
PMID: 27895058
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute