<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/NCT04490707</url>
  </required_header>
  <id_info>
    <org_study_id>ZDYYGZ202005</org_study_id>
    <nct_id>NCT04490707</nct_id>
  </id_info>
  <brief_title>Study of Azacytidine Combined With Lenalidomide As Maintenance Therapy Based on MRD Monitoring in AML</brief_title>
  <official_title>Clinical Study of Azacytidine Combined With Lenalidomide As Maintenance Therapy Based on MRD Monitoring In Elderly or Unfit Patients With Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ge Zheng</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhongda Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Great progress has been witnessed on the treatment of acute myeloid leukemia (AML) in recent&#xD;
      years. However, elderly patients ineligible for receiving high dose chemotherapy and&#xD;
      allo-HSCT, have high relapse rate and treatment-related complications. Azacitidine (AZA), a&#xD;
      listed hypomethylating agent in China in 2018, is the only approved demethylating drug in the&#xD;
      treatment of AML, following the NCCN guidelines. In addition, lenalidomide(LEN) has been&#xD;
      shown to rapidly enhance cytotoxic T- and natural killer (NK)-cell function and reduce&#xD;
      relapse post-chemotherapy in patients with MM, also has substantial activity as a single&#xD;
      agent in elderly patients with AML. Measurable residual disease (MRD) has been proven to be&#xD;
      highly prognostic in quite a number clinical studies. This study is aimed to validate the&#xD;
      efficacy and safety advantages of the maintenance therapy that contain AZA and LEN in elderly&#xD;
      or unfit for intensive therapy patients with AML based on MRD monitoring.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, elderly or unfit for intensive therapy AML patients who had achieved complete&#xD;
      remission(CR) after remission-induction and consolidation chemotherapy were assigned to 3&#xD;
      Arms: (1) Maintenance therapy with AZA combined with LEN（AZA+LEN）: AZA 50mg/m² per day for&#xD;
      days 1-5 and LEN 10mg per day orally for days 6-26 , every 28 days for up to 12 cycles or&#xD;
      progression; (2) Maintenance therapy with AZA only: AZA 50mg/m² per day for days 1-5, every&#xD;
      28 days for up to 12 cycles or progression; (3) Observation or with supporting therapy. MRD&#xD;
      will be assessed by flow cytometry and molecular techniques. The efficacy and safety of the 3&#xD;
      Arms will be evaluated in this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DFS</measure>
    <time_frame>From date of randomization or complete remission until the date of first documented disease progression from any cause,assessed up to 100weeks</time_frame>
    <description>DFS in months, in present of disease free survival period of all participants</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OS</measure>
    <time_frame>From date of randomization until the date of first documented death from any cause or end of this study, whichever come first,assessed up to 100weeks</time_frame>
    <description>OS in months, in present of over all survival period of all participants</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events rates</measure>
    <time_frame>From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks</time_frame>
    <description>Adverse events rates in percentage</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Acute Myeloid Leukemia in Remission</condition>
  <arm_group>
    <arm_group_label>Azacitidine plus Lenalidomide (AZA+LEN)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 1(AZA+LEN): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter maintenance therapy with AZA combined with LEN: AZA 50mg/m² per day for days 1-5 and LEN 10mg per day orally for days 6-26 , every 28 days for up to 12 cycles or progression.&#xD;
AZA -Azacitidine, LEN- Lenalidomide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Azacitidine(AZA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 2 (AZA): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter maintenance therapy with AZA 50mg/m² per day for days 1-5, every 28 days for up to 12 cycles or progression.&#xD;
AZA -Azacitidine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Arm 3(Observation): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter observation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azacitidine</intervention_name>
    <description>Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Azacitidine</description>
    <arm_group_label>Azacitidine plus Lenalidomide (AZA+LEN)</arm_group_label>
    <arm_group_label>Azacitidine(AZA)</arm_group_label>
    <other_name>AZA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Lenalidomide</description>
    <arm_group_label>Azacitidine plus Lenalidomide (AZA+LEN)</arm_group_label>
    <other_name>LEN</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with acute myeloid leukemia.Meet the criteria of the 2016 WHO classification&#xD;
             system(APL were excluded), based on morphology, immunology, cytogenetics and molecular&#xD;
             biology (MICM) diagnosis.&#xD;
&#xD;
          -  Complete remission was evaluated according to 2020 NCCN guidelines after induction&#xD;
             treatment.&#xD;
&#xD;
          -  Patients with age≥ 60 years; or age&lt;60 years unfit for intensive chemotherapy.&#xD;
&#xD;
          -  Volunteered to sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mental disorders or other conditions that cannot meet the requirements of research,&#xD;
             treatment and monitoring.&#xD;
&#xD;
          -  Allergic to Azacytidine, Lenalidomide , or other drugs of this study&#xD;
&#xD;
          -  Age over 80 years.&#xD;
&#xD;
          -  Any other conditions considered by the study investigators that are not suitable for&#xD;
             participating in this clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zheng Ge, M.D, Ph.D</last_name>
    <role>Study Director</role>
    <affiliation>Zhongda Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zheng Ge, M.D, Ph.D</last_name>
    <phone>02583262468</phone>
    <email>Janege879@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210009</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zheng Ge, M.D, Ph.D</last_name>
      <phone>02583262468</phone>
      <email>Janege879@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>March 23, 2022</last_update_submitted>
  <last_update_submitted_qc>March 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Zhongda Hospital</investigator_affiliation>
    <investigator_full_name>Ge Zheng</investigator_full_name>
    <investigator_title>Director of Department of Hematology</investigator_title>
  </responsible_party>
  <keyword>Acute myeloid leukemia</keyword>
  <keyword>Azacitidine</keyword>
  <keyword>Lenalidomide</keyword>
  <keyword>Maintenance Therapy</keyword>
  <keyword>MRD</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Azacitidine</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/NCT04490707
org study id: ZDYYGZ202005
nct id: NCT04490707
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Great progress has been witnessed on the treatment of acute myeloid leukemia (AML) in recent
      years. However, elderly patients ineligible for receiving high dose chemotherapy and
      allo-HSCT, have high relapse rate and treatment-related complications. Azacitidine (AZA), a
      listed hypomethylating agent in China in 2018, is the only approved demethylating drug in the
      treatment of AML, following the NCCN guidelines. In addition, lenalidomide(LEN) has been
      shown to rapidly enhance cytotoxic T- and natural killer (NK)-cell function and reduce
      relapse post-chemotherapy in patients with MM, also has substantial activity as a single
      agent in elderly patients with AML. Measurable residual disease (MRD) has been proven to be
      highly prognostic in quite a number clinical studies. This study is aimed to validate the
      efficacy and safety advantages of the maintenance therapy that contain AZA and LEN in elderly
      or unfit for intensive therapy patients with AML based on MRD monitoring.
In this study, elderly or unfit for intensive therapy AML patients who had achieved complete
      remission(CR) after remission-induction and consolidation chemotherapy were assigned to 3
      Arms: (1) Maintenance therapy with AZA combined with LEN（AZA+LEN）: AZA 50mg/m² per day for
      days 1-5 and LEN 10mg per day orally for days 6-26 , every 28 days for up to 12 cycles or
      progression; (2) Maintenance therapy with AZA only: AZA 50mg/m² per day for days 1-5, every
      28 days for up to 12 cycles or progression; (3) Observation or with supporting therapy. MRD
      will be assessed by flow cytometry and molecular techniques. The efficacy and safety of the 3
      Arms will be evaluated in this study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DFS
time frame: From date of randomization or complete remission until the date of first documented disease progression from any cause,assessed up to 100weeks
description: DFS in months, in present of disease free survival period of all participants
measure: OS
time frame: From date of randomization until the date of first documented death from any cause or end of this study, whichever come first,assessed up to 100weeks
description: OS in months, in present of over all survival period of all participants
measure: Adverse events rates
time frame: From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks
description: Adverse events rates in percentage
arm group label: Azacitidine plus Lenalidomide (AZA+LEN)
arm group type: Experimental
description: Arm 1(AZA+LEN): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter maintenance therapy with AZA combined with LEN: AZA 50mg/m² per day for days 1-5 and LEN 10mg per day orally for days 6-26 , every 28 days for up to 12 cycles or progression.
AZA -Azacitidine, LEN- Lenalidomide
arm group label: Azacitidine(AZA)
arm group type: Experimental
description: Arm 2 (AZA): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter maintenance therapy with AZA 50mg/m² per day for days 1-5, every 28 days for up to 12 cycles or progression.
AZA -Azacitidine
arm group label: Observation
arm group type: No Intervention
description: Arm 3(Observation): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter observation.
intervention type: Drug
intervention name: Azacitidine
description: Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Azacitidine
arm group label: Azacitidine plus Lenalidomide (AZA+LEN)
arm group label: Azacitidine(AZA)
other name: AZA
intervention type: Drug
intervention name: Lenalidomide
description: Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Lenalidomide
arm group label: Azacitidine plus Lenalidomide (AZA+LEN)
other name: LEN
criteria: 
gender: All
minimum age: 60 Years
maximum age: 80 Years
healthy volunteers: No
last name: Zheng Ge, M.D, Ph.D
role: Study Director
affiliation: Zhongda Hospital
last name: Zheng Ge, M.D, Ph.D
phone: 02583262468
email: Janege879@hotmail.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Zhongda Hospital
investigator full name: Ge Zheng
investigator title: Director of Department of Hematology
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Lenalidomide
mesh term: Azacitidine
sharing ipd: No