<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/NCT03031249</url>
  </required_header>
  <id_info>
    <org_study_id>IIT2016007-EC-1-2</org_study_id>
    <nct_id>NCT03031249</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia</brief_title>
  <official_title>Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Hematology &amp; Blood Diseases Hospital, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Hematology &amp; Blood Diseases Hospital, China</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>
      In this open-label, randomized, prospective clinical trial, nucleophosmin-1(NPM1) mutated&#xD;
      acute myeloid leukemia (AML) patients who have reached CR are randomized into two groups.The&#xD;
      control group receive high-dose cytarabine(HDAC) regimen while the experimental group receive&#xD;
      high dose of cytarabine plus tretinoin(ATRA) and arsenic trioxide(ATO) treatment.The safety&#xD;
      and efficacy of ATRA and ATO is evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this open-label, randomized, prospective clinical trial, NPM1- mutated AML patients who&#xD;
      have reached CR are randomized into two groups.&#xD;
&#xD;
      In experimental group, patients receive cytarabine at a dose of 3g/㎡/d on the first, third&#xD;
      and fifth day, ATRA at a dose of 30mg/㎡/d on day 1-14 and ATO at a dose of 0.15mg/kg/d&#xD;
      (maximum, 10mg/d) on day 1-14. Patients in control group only receive high dose of&#xD;
      cytarabine.&#xD;
&#xD;
      The safety and efficacy of ATRA plus ATO regimen is evaluated.The primary outcome is&#xD;
      relapse-free survival rate after treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 8, 2017</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relapse-Free Survival Rate (RFS)</measure>
    <time_frame>Within 5 years after randomization</time_frame>
    <description>RFS is defined as the time from the date of complete remission (CR) after entry in this trial until the date of documented relapse or death for NPM1 mutated leukemia patients who achieve CR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non-relapse Mortality</measure>
    <time_frame>through treatment completion, an average of 5 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Rate (OS)</measure>
    <time_frame>Within 5 years after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of relapse</measure>
    <time_frame>Within 5 years after randomization</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>AML</condition>
  <arm_group>
    <arm_group_label>High Dose of Cytarabine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive high dose of cytarabine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HDAC + ATRA + ATO</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive high dose of cytarabine plus ATRA and ATO treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Cytarabine at a dose of 3g/㎡/d on the first, third and fifth day.</description>
    <arm_group_label>HDAC + ATRA + ATO</arm_group_label>
    <arm_group_label>High Dose of Cytarabine</arm_group_label>
    <other_name>HDAC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>all-trans retinoic acid</intervention_name>
    <description>ATRA at a dose of 30mg/㎡/d on day 1-14.</description>
    <arm_group_label>HDAC + ATRA + ATO</arm_group_label>
    <other_name>ATRA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Arsenic Trioxide</intervention_name>
    <description>ATO at a dose of 10mg/d on day 1-14</description>
    <arm_group_label>HDAC + ATRA + ATO</arm_group_label>
    <other_name>ATO</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age of 14 to 55 years old;&#xD;
&#xD;
          2. Patients that meet the diagnostic criteria(WHO 2008 criteria) of AML (except APL&#xD;
             subtypes) and with NPM1-mutated.&#xD;
&#xD;
          3. Reached CR after induction regimen.&#xD;
&#xD;
          4. ECOG score of ≤ 2;&#xD;
&#xD;
          5. Patients with eligible laboratory examination including liver,renal and heart&#xD;
             function.&#xD;
&#xD;
          6. Adult patients are willing to participate in the study and sign the informed consent&#xD;
             by themselves or by their immediate family. Patients under 18 years old willing to&#xD;
             participate should have their legal guardians sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Secondary leukemia.&#xD;
&#xD;
          2. Patients had other tumor at active stage or had received radiotherapy or chemotherapy&#xD;
             in the last 6 months due to other tumor.&#xD;
&#xD;
          3. Patients with other blood diseases(for example, haemophiliacs) are excluded.However,&#xD;
             patients with abnormal blood count, but with undiagnosed MDS or MPD patients are&#xD;
             included.&#xD;
&#xD;
          4. Acute panmyelosis with myelofibrosis and myeloid sarcoma patients;&#xD;
&#xD;
          5. With BCR-ABL fusion gene;&#xD;
&#xD;
          6. Pregnant or lactating women;&#xD;
&#xD;
          7. With ineligible renal or liver function;&#xD;
&#xD;
          8. With active cardiovascular disease;&#xD;
&#xD;
          9. Severe infection disease including uncured tuberculosis pulmonary aspergillosis;&#xD;
&#xD;
         10. AIDS;&#xD;
&#xD;
         11. Patients had central nervous system involvement when they were diagnosed as AML.&#xD;
&#xD;
         12. Patients with epilepsy or dementia or other mental disease who couldn't understand or&#xD;
             follow the research.&#xD;
&#xD;
         13. Drugs, medical, mental or social situation may distract patients from following the&#xD;
             research or being evaluated the results.&#xD;
&#xD;
         14. Patients with other factors which were considered unsuitable to participate in the&#xD;
             study by the investigators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianxiang Wang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lijun Liu</last_name>
    <phone>86-22-23909237</phone>
    <email>bloodgcp@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Hematology &amp; Blood Diseases Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>lijun Liu</last_name>
      <phone>86-22-23909237</phone>
      <email>bloodgcp@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>March 19, 2020</last_update_submitted>
  <last_update_submitted_qc>March 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</investigator_affiliation>
    <investigator_full_name>wang, jianxiang</investigator_full_name>
    <investigator_title>Director of Diagnosis and Treatment Center for Leukemia</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Tretinoin</mesh_term>
    <mesh_term>Arsenic Trioxide</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/NCT03031249
org study id: IIT2016007-EC-1-2
nct id: NCT03031249
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In this open-label, randomized, prospective clinical trial, nucleophosmin-1(NPM1) mutated
      acute myeloid leukemia (AML) patients who have reached CR are randomized into two groups.The
      control group receive high-dose cytarabine(HDAC) regimen while the experimental group receive
      high dose of cytarabine plus tretinoin(ATRA) and arsenic trioxide(ATO) treatment.The safety
      and efficacy of ATRA and ATO is evaluated.
In this open-label, randomized, prospective clinical trial, NPM1- mutated AML patients who
      have reached CR are randomized into two groups.

      In experimental group, patients receive cytarabine at a dose of 3g/㎡/d on the first, third
      and fifth day, ATRA at a dose of 30mg/㎡/d on day 1-14 and ATO at a dose of 0.15mg/kg/d
      (maximum, 10mg/d) on day 1-14. Patients in control group only receive high dose of
      cytarabine.

      The safety and efficacy of ATRA plus ATO regimen is evaluated.The primary outcome is
      relapse-free survival rate after treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Relapse-Free Survival Rate (RFS)
time frame: Within 5 years after randomization
description: RFS is defined as the time from the date of complete remission (CR) after entry in this trial until the date of documented relapse or death for NPM1 mutated leukemia patients who achieve CR.
measure: Non-relapse Mortality
time frame: through treatment completion, an average of 5 months
measure: Overall Survival Rate (OS)
time frame: Within 5 years after randomization
measure: Cumulative incidence of relapse
time frame: Within 5 years after randomization
arm group label: High Dose of Cytarabine
arm group type: Active Comparator
description: Patients receive high dose of cytarabine.
arm group label: HDAC + ATRA + ATO
arm group type: Experimental
description: Patients receive high dose of cytarabine plus ATRA and ATO treatment.
intervention type: Drug
intervention name: Cytarabine
description: Cytarabine at a dose of 3g/㎡/d on the first, third and fifth day.
arm group label: HDAC + ATRA + ATO
arm group label: High Dose of Cytarabine
other name: HDAC
intervention type: Drug
intervention name: all-trans retinoic acid
description: ATRA at a dose of 30mg/㎡/d on day 1-14.
arm group label: HDAC + ATRA + ATO
other name: ATRA
intervention type: Drug
intervention name: Arsenic Trioxide
description: ATO at a dose of 10mg/d on day 1-14
arm group label: HDAC + ATRA + ATO
other name: ATO
criteria: 
gender: All
minimum age: 14 Years
maximum age: 55 Years
healthy volunteers: No
last name: Jianxiang Wang
role: Principal Investigator
affiliation: Institute of Hematology & Blood Diseases Hospital, China
last name: Lijun Liu
phone: 86-22-23909237
email: bloodgcp@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Institute of Hematology & Blood Diseases Hospital, China
investigator full name: wang, jianxiang
investigator title: Director of Diagnosis and Treatment Center for Leukemia
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine
mesh term: Tretinoin
mesh term: Arsenic Trioxide
sharing ipd: No