<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/NCT04424147</url>
  </required_header>
  <id_info>
    <org_study_id>HVA in rrAML</org_study_id>
    <nct_id>NCT04424147</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of HVA Regimens as Salvage Treatment in rrAML</brief_title>
  <official_title>Efficacy and Safety of HVA Regimens as Salvage Treatment in Relapsed/Refractory (rr) Acute Myeloid Leukemia (AML)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanfang Hospital, Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shenzhen Second People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Seventh Affiliated Hospital of Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Maoming People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sun Yat-sen Memorial Hospital,Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shenzhen Hospital, Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First People's Hospital of Chenzhou</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University Shenzhen Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhongshan People's Hospital, Guangdong, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nanfang Hospital, Southern Medical University</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>
      Up Until now, there is not well acepted treatment for relapsed/refractory (rr) acute myeloid&#xD;
      luekemia (AML), which has low complete response and poor survival. According to different&#xD;
      guildlines, clinical trial is the first choice for the treatment of rrAML. High expression of&#xD;
      BCL-2 and hypermethylation are very important factors for drug resistance in AML. Lots of&#xD;
      studies have reported combination of BCL-2 inhibitor with hypomethylating agents (HMA) showed&#xD;
      a promising efficacy in elder or unfit patients with newly diagnosed AML, however, presented&#xD;
      not that exciting curing effect in rrAML. It is known that overexpression of MCL-1 and BCL-XL&#xD;
      is the main reason for leukemia cells being resistant to BCL2 inhibitors. Since&#xD;
      Homoharringtonine (HHT) could downregulate MCL-1 and BCL-XL in leukemia cells, there might be&#xD;
      a synergic effect for combination of BCL-2 inhibitors with HHT, which has been proven in the&#xD;
      treatment of lymphoma. Yet, there is not a report for the use of this combination in AML. In&#xD;
      this single arm multi-centers prospective study, adult patients with rrAML are included and&#xD;
      treated with BCL-2 inhibitor venetoclax at a dose of 400mg per day for 14 days, combined with&#xD;
      azacitidine (AZA) at a dose of 75mg/m2 per day for 7 days, and HHT 1mg/m2 per day for 7 days,&#xD;
      and then the eficacy and safety of HVA regimens as salvage treatment in rrAML are assessed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 27, 2020</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 16, 2021</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Patients with rrAML are treated with HVA regimen</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete response</measure>
    <time_frame>At the end of Cycle 2 (each cycle is 28 days)</time_frame>
    <description>Blast rate lower than 5% with or without peripheral blood cell recover</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of HVA treatment</measure>
    <time_frame>At the end of Cycle 2 (each cycle is 28 days)</time_frame>
    <description>The number of participants experiencing 3/4 degree bone marrow suppession and infection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>one year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">96</enrollment>
  <condition>Refractory Acute Myeloid Leukemia</condition>
  <condition>Relapsed Acute Erythroid Leukemia</condition>
  <condition>Salvage Treatment</condition>
  <condition>HVA Regimen</condition>
  <arm_group>
    <arm_group_label>HVA treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients with rrAML are treated with HVA regimen</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>HVA Regimens as Salvage Treatment</intervention_name>
    <description>venetoclax with a dose of 400mg per day for 14 days, combined with azacitidine (AZA) with a dose of 75mg/m2 per day for 7 days, and HHT 1mg/m2 per day for 7 days</description>
    <arm_group_label>HVA treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with rrAML Patients with the age of 18-65 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood&#xD;
             pressure)&#xD;
&#xD;
          -  Patients with any conditions not suitable for the trial (investigators' decision)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qifa Liu</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nanfang Hospital, Southern Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Hematology,Nanfang Hospital, Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>October 24, 2022</last_update_submitted>
  <last_update_submitted_qc>October 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nanfang Hospital, Southern Medical University</investigator_affiliation>
    <investigator_full_name>Qifa Liu</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>
    <mesh_term>Leukemia, Erythroblastic, Acute</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/NCT04424147
org study id: HVA in rrAML
nct id: NCT04424147
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Up Until now, there is not well acepted treatment for relapsed/refractory (rr) acute myeloid
      luekemia (AML), which has low complete response and poor survival. According to different
      guildlines, clinical trial is the first choice for the treatment of rrAML. High expression of
      BCL-2 and hypermethylation are very important factors for drug resistance in AML. Lots of
      studies have reported combination of BCL-2 inhibitor with hypomethylating agents (HMA) showed
      a promising efficacy in elder or unfit patients with newly diagnosed AML, however, presented
      not that exciting curing effect in rrAML. It is known that overexpression of MCL-1 and BCL-XL
      is the main reason for leukemia cells being resistant to BCL2 inhibitors. Since
      Homoharringtonine (HHT) could downregulate MCL-1 and BCL-XL in leukemia cells, there might be
      a synergic effect for combination of BCL-2 inhibitors with HHT, which has been proven in the
      treatment of lymphoma. Yet, there is not a report for the use of this combination in AML. In
      this single arm multi-centers prospective study, adult patients with rrAML are included and
      treated with BCL-2 inhibitor venetoclax at a dose of 400mg per day for 14 days, combined with
      azacitidine (AZA) at a dose of 75mg/m2 per day for 7 days, and HHT 1mg/m2 per day for 7 days,
      and then the eficacy and safety of HVA regimens as salvage treatment in rrAML are assessed.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Patients with rrAML are treated with HVA regimen
primary purpose: Treatment
masking: None (Open Label)
measure: Complete response
time frame: At the end of Cycle 2 (each cycle is 28 days)
description: Blast rate lower than 5% with or without peripheral blood cell recover
measure: Safety and Tolerability of HVA treatment
time frame: At the end of Cycle 2 (each cycle is 28 days)
description: The number of participants experiencing 3/4 degree bone marrow suppession and infection.
measure: Disease-free survival
time frame: one year
measure: Overall survival
time frame: one year
arm group label: HVA treatment
arm group type: Experimental
description: All patients with rrAML are treated with HVA regimen
intervention type: Combination Product
intervention name: HVA Regimens as Salvage Treatment
description: venetoclax with a dose of 400mg per day for 14 days, combined with azacitidine (AZA) with a dose of 75mg/m2 per day for 7 days, and HHT 1mg/m2 per day for 7 days
arm group label: HVA treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Qifa Liu
role: Principal Investigator
affiliation: Nanfang Hospital, Southern Medical University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Nanfang Hospital, Southern Medical University
investigator full name: Qifa Liu
investigator title: Professor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Leukemia, Erythroblastic, Acute
sharing ipd: No