<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/NCT04446806</url>
  </required_header>
  <id_info>
    <org_study_id>APL-01</org_study_id>
    <nct_id>NCT04446806</nct_id>
  </id_info>
  <brief_title>Prevention and Treatment of Differentiation Syndrome in Patients With Acute Promyelocytic Leukemia</brief_title>
  <official_title>A Prospective Single Center Study of Prevention and Treatment of Differentiation Syndrome in Patients With Acute Promyelocytic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital of Soochow University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The First Affiliated Hospital of Soochow University</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>
      With the introduction of all-trans-retinoic acid (ATRA) and arsenic,the outcome of patients&#xD;
      with acute promyelocytic leukemia (APL)has been improved considerably over the last&#xD;
      decades.However，early deaths (EDs), mainly due to APL-specific coagulopathy, differentiation&#xD;
      syndrome (DS)emerge as a major threat to APL patients.We observe and evaluate the effectivity&#xD;
      of induction therapy in patients with APL. Administrate intravenous dexamethasone to prevent&#xD;
      or preemptive treat DS. Assess the efficacy and safety of ruxolitinib as second treatment in&#xD;
      patients with severe DS with no respond to dexamethasone.Furthermore，the changes of spectrum&#xD;
      of cytokines are monitered to find the relationship between the cytokines and the severity of&#xD;
      DS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Adults ages 18-75 with primary acute promyelocytic leukemia.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      The induction therapy with ATRA 25mg/m2/d and ATO 10mg/kg/d should be started as soon as the&#xD;
      diagnosis of APL confirmed.&#xD;
&#xD;
      Intravenous dexamethasone at a dose of 5-20 mg daily must be started if the WBC count greater&#xD;
      than 5e+9/L (before or during the treatment with ATRA) as prevention or preemptive therapy of&#xD;
      DS.&#xD;
&#xD;
      Idarubicin (4-10 mg/m2 /d*3d) and hydroxyurea（1.0-3.0g/d）can be given as leukocyte lowering&#xD;
      therapy which may lessen the risk of DS.&#xD;
&#xD;
      When the progression of clinical symptoms of DS with no response to dexamethasone,ATRA must&#xD;
      be stopped and ruxolitinib (5-20mg /d) should be administrated to reduce the production of&#xD;
      cytokines.&#xD;
&#xD;
      Participants should stay in the hospital during the treatment for about 4 weeks.&#xD;
&#xD;
      The changes of spectrum of cytokines are monitored to discover the potential relationship&#xD;
      between the cytokines and the severity of DS.&#xD;
&#xD;
      Participants will visit every 1 months after CR for 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Anticipated">May 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>complete remission rate</measure>
    <time_frame>during the induction treatment</time_frame>
    <description>complete remission rate after treated by the induction regimen with ATRA and Arsenite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>incidence and severity of differentiation syndrome</measure>
    <time_frame>during the induction treatment</time_frame>
    <description>All symptoms and signs associated to DS should be paid closely attention to.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>from the day of first patient treatment up to 36 months after the last patient's enrollment</time_frame>
    <description>from the date of inclusion to date of death, irrespective of cause</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Safety and Efficacy</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Ruxolitinib as second treatment in patients with severe DS failed in responding to hormone.Furthermore</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of primary acute promyelocytic leukemia.&#xD;
&#xD;
          -  ECOG score≤3.&#xD;
&#xD;
          -  Must be able to understand and willing to participate in the study and sign the&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refractory/secondary acute promyelocytic leukemia.&#xD;
&#xD;
          -  Severe complications such as myocardial infarction, chronic cardiac insufficiency,&#xD;
             hepatic failure, renal insufficiency, etc.&#xD;
&#xD;
          -  Clinically uncontrolled active infections.&#xD;
&#xD;
          -  Malignant tumors with other progresses.&#xD;
&#xD;
          -  Ecg: QT interval &gt; 450 ms.&#xD;
&#xD;
          -  Allergic to arsenic agent.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qian Wu</last_name>
    <role>Study Chair</role>
    <affiliation>First Affiliated Hospital, Soochow University Suzhou, Jiangsu, China, 215000</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Suning Chen</last_name>
    <phone>8613814881746</phone>
    <email>chensuning@sina.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Qian Wu</last_name>
    <phone>8613656205608</phone>
    <email>42732890@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>First Affiliated Hospital, Soochow University</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <zip>215000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Qian Wu</last_name>
      <phone>8613656205608</phone>
      <email>42732890@qq.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>March 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia, Promyelocytic, 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/NCT04446806
org study id: APL-01
nct id: NCT04446806
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
With the introduction of all-trans-retinoic acid (ATRA) and arsenic,the outcome of patients
      with acute promyelocytic leukemia (APL)has been improved considerably over the last
      decades.However，early deaths (EDs), mainly due to APL-specific coagulopathy, differentiation
      syndrome (DS)emerge as a major threat to APL patients.We observe and evaluate the effectivity
      of induction therapy in patients with APL. Administrate intravenous dexamethasone to prevent
      or preemptive treat DS. Assess the efficacy and safety of ruxolitinib as second treatment in
      patients with severe DS with no respond to dexamethasone.Furthermore，the changes of spectrum
      of cytokines are monitered to find the relationship between the cytokines and the severity of
      DS.
Adults ages 18-75 with primary acute promyelocytic leukemia.

      Design:

      The induction therapy with ATRA 25mg/m2/d and ATO 10mg/kg/d should be started as soon as the
      diagnosis of APL confirmed.

      Intravenous dexamethasone at a dose of 5-20 mg daily must be started if the WBC count greater
      than 5e+9/L (before or during the treatment with ATRA) as prevention or preemptive therapy of
      DS.

      Idarubicin (4-10 mg/m2 /d*3d) and hydroxyurea（1.0-3.0g/d）can be given as leukocyte lowering
      therapy which may lessen the risk of DS.

      When the progression of clinical symptoms of DS with no response to dexamethasone,ATRA must
      be stopped and ruxolitinib (5-20mg /d) should be administrated to reduce the production of
      cytokines.

      Participants should stay in the hospital during the treatment for about 4 weeks.

      The changes of spectrum of cytokines are monitored to discover the potential relationship
      between the cytokines and the severity of DS.

      Participants will visit every 1 months after CR for 3 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: complete remission rate
time frame: during the induction treatment
description: complete remission rate after treated by the induction regimen with ATRA and Arsenite
measure: incidence and severity of differentiation syndrome
time frame: during the induction treatment
description: All symptoms and signs associated to DS should be paid closely attention to.
measure: overall survival
time frame: from the day of first patient treatment up to 36 months after the last patient's enrollment
description: from the date of inclusion to date of death, irrespective of cause
intervention type: Drug
intervention name: Ruxolitinib
description: Ruxolitinib as second treatment in patients with severe DS failed in responding to hormone.Furthermore
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Qian Wu
role: Study Chair
affiliation: First Affiliated Hospital, Soochow University Suzhou, Jiangsu, China, 215000
last name: Suning Chen
phone: 8613814881746
email: chensuning@sina.com
last name: Qian Wu
phone: 8613656205608
email: 42732890@qq.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Leukemia, Promyelocytic, Acute
sharing ipd: No