<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/NCT04454580</url>
  </required_header>
  <id_info>
    <org_study_id>HMA-V</org_study_id>
    <nct_id>NCT04454580</nct_id>
  </id_info>
  <brief_title>Hypomethylating Agents and Venetoclax in Newly Diagnosed Acute Myeloid Leukemia Patients Not Eligible for Intensive Chemotherapy</brief_title>
  <official_title>Retrospective, Observational, Monocentric Study to Assess Efficacy and Safety of the Combination of an Hypomethylating Agent in Combination With Venetoclax for Newly Diagnosed Acute Myeloid Leukemia Patients Not Eligible for Intensive Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ospedale Maggiore Di Trieste</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ospedale Maggiore Di Trieste</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a retrospective, observational, monocentric study to evaluate the efficacy and safety&#xD;
      of the combination of an hypomethylating agent with venetoclax newly diagnosed patients with&#xD;
      acute myeloid leukemia ineligible for intensive chemotherapy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The prognosis of acute myeloid leukemia (AML) patients who are ineligible for intensive&#xD;
      chemotherapy is poor (Kantarjian et al). Hypomethylating agents, azacitidine and decitabine,&#xD;
      are effective and less toxic regimens, and treatment with these agents has improved the&#xD;
      prognosis of these patients (Fenaux et al).&#xD;
&#xD;
      Venetoclax, a Bcl-2 inhibitor, in combination with azacitidine has shown efficacy in AML&#xD;
      patients with complete remission rate of 73% and overall survival at 2 years of 40-50% (Di&#xD;
      Nardo et al).&#xD;
&#xD;
      On these grounds, the aim of this study is to collect the real-life experience with this&#xD;
      combination in previously untreated AML patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 16, 2020</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Complete response (CR) rate</measure>
    <time_frame>every three months after started treatment up to two years</time_frame>
    <description>according to European Leukemia Network (ELN)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>every three months after started treatment up to two years</time_frame>
    <description>according to European Leukemia Network (ELN)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morphologic leukemia-free state (MLFS)</measure>
    <time_frame>every three months after started treatment up to two years</time_frame>
    <description>according to European Leukemia Network (ELN)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free-survival</measure>
    <time_frame>from the start of the treatment until the date of documented progression or date of death from any cause, assessed up to 2 years</time_frame>
    <description>from start of the treatment to progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>from the start of the treatment until the date of documented progression or date of death from any cause, assessed up to 2 years</time_frame>
    <description>from start of the treatment to progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events and serious adverse events</measure>
    <time_frame>through study completion, for an average of 1 year</time_frame>
    <description>according to CTCAE v. 4.0</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Acute Myeloid Leukemia, Adult</condition>
  <condition>Hypomethylating Agents</condition>
  <condition>Venetoclax</condition>
  <arm_group>
    <arm_group_label>treated patients</arm_group_label>
    <description>hypomethylating agent (azacitidine or decitabine) in combination with venetoclax</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>treatment with azacitidine or decitabine in combination with venetoclax</description>
    <arm_group_label>treated patients</arm_group_label>
    <other_name>Azacitidine</other_name>
    <other_name>Decitabine</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population includes adult patients with newly diagnosed acute myeloid leukemia&#xD;
        not eligible for intensive chemotherapy, treated in a referral center for hematology&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age ≥18 years&#xD;
&#xD;
          -  newly diagnosed acute myeloid leukemia not eligible for intensive chemotherapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  promyelocytic acute myeloid leukemia&#xD;
&#xD;
          -  patients who have already received one or more prior lines of therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Francesco Zaja, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>SC Ematologia Ospedale Maggiore Trieste</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Francesco Zaja, Professor</last_name>
    <phone>+390403992888</phone>
    <email>francesco.zaja@asugi.sanita.fvg.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>SC Ematologia Ospedale Maggiore</name>
      <address>
        <city>Trieste</city>
        <zip>34100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francesco Zaja, Professor</last_name>
      <phone>+390403992888</phone>
      <email>francesco.zaja@asugi.sanita.fvg.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. doi: 10.1200/JCO.2009.23.8329. Epub 2009 Dec 21.</citation>
    <PMID>20026804</PMID>
  </reference>
  <reference>
    <citation>DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25.</citation>
    <PMID>30361262</PMID>
  </reference>
  <results_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>
  </results_reference>
  <results_reference>
    <citation>Kantarjian H, Ravandi F, O'Brien S, Cortes J, Faderl S, Garcia-Manero G, Jabbour E, Wierda W, Kadia T, Pierce S, Shan J, Keating M, Freireich EJ. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010 Nov 25;116(22):4422-9. doi: 10.1182/blood-2010-03-276485. Epub 2010 Jul 28.</citation>
    <PMID>20668231</PMID>
  </results_reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>September 14, 2020</last_update_submitted>
  <last_update_submitted_qc>September 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ospedale Maggiore Di Trieste</investigator_affiliation>
    <investigator_full_name>Francesco Zaja</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azacitidine</mesh_term>
    <mesh_term>Decitabine</mesh_term>
    <mesh_term>Venetoclax</mesh_term>
  </intervention_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/NCT04454580
org study id: HMA-V
nct id: NCT04454580
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a retrospective, observational, monocentric study to evaluate the efficacy and safety
      of the combination of an hypomethylating agent with venetoclax newly diagnosed patients with
      acute myeloid leukemia ineligible for intensive chemotherapy
The prognosis of acute myeloid leukemia (AML) patients who are ineligible for intensive
      chemotherapy is poor (Kantarjian et al). Hypomethylating agents, azacitidine and decitabine,
      are effective and less toxic regimens, and treatment with these agents has improved the
      prognosis of these patients (Fenaux et al).

      Venetoclax, a Bcl-2 inhibitor, in combination with azacitidine has shown efficacy in AML
      patients with complete remission rate of 73% and overall survival at 2 years of 40-50% (Di
      Nardo et al).

      On these grounds, the aim of this study is to collect the real-life experience with this
      combination in previously untreated AML patients.
observational model: Case-Only
time perspective: Retrospective
measure: Complete response (CR) rate
time frame: every three months after started treatment up to two years
description: according to European Leukemia Network (ELN)
measure: Overall response rate (ORR)
time frame: every three months after started treatment up to two years
description: according to European Leukemia Network (ELN)
measure: Morphologic leukemia-free state (MLFS)
time frame: every three months after started treatment up to two years
description: according to European Leukemia Network (ELN)
measure: Progression-free-survival
time frame: from the start of the treatment until the date of documented progression or date of death from any cause, assessed up to 2 years
description: from start of the treatment to progression or death
measure: Overall survival
time frame: from the start of the treatment until the date of documented progression or date of death from any cause, assessed up to 2 years
description: from start of the treatment to progression or death
measure: adverse events and serious adverse events
time frame: through study completion, for an average of 1 year
description: according to CTCAE v. 4.0
arm group label: treated patients
description: hypomethylating agent (azacitidine or decitabine) in combination with venetoclax
intervention type: Drug
intervention name: Venetoclax
description: treatment with azacitidine or decitabine in combination with venetoclax
arm group label: treated patients
other name: Azacitidine
other name: Decitabine
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Francesco Zaja, Professor
role: Principal Investigator
affiliation: SC Ematologia Ospedale Maggiore Trieste
last name: Francesco Zaja, Professor
phone: +390403992888
email: francesco.zaja@asugi.sanita.fvg.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. doi: 10.1200/JCO.2009.23.8329. Epub 2009 Dec 21.
PMID: 20026804
citation: DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25.
PMID: 30361262
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
citation: Kantarjian H, Ravandi F, O'Brien S, Cortes J, Faderl S, Garcia-Manero G, Jabbour E, Wierda W, Kadia T, Pierce S, Shan J, Keating M, Freireich EJ. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010 Nov 25;116(22):4422-9. doi: 10.1182/blood-2010-03-276485. Epub 2010 Jul 28.
PMID: 20668231
responsible party type: Principal Investigator
investigator affiliation: Ospedale Maggiore Di Trieste
investigator full name: Francesco Zaja
investigator title: Professor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Azacitidine
mesh term: Decitabine
mesh term: Venetoclax
sharing ipd: No