<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/NCT03239886</url>
  </required_header>
  <id_info>
    <org_study_id>15418</org_study_id>
    <nct_id>NCT03239886</nct_id>
  </id_info>
  <brief_title>Imatinib Discontinuation in Patients With Chronic Myeloid Leukemia Chronic Phase With Sustained MR4log</brief_title>
  <official_title>Imatinib Discontinuation in Patients With Chronic Myeloid Leukemia Chronic Phase With Sustained MR4log</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo General Hospital</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>
      This study will evaluate the proportion of subjects with chronic myeloid leukemia chronic&#xD;
      phase that sustain major molecular response after imatinib discontinuation. To be eligible&#xD;
      for this protocol, the subject must have received imatinib as first line regiment for at&#xD;
      least 3 years with sustained molecular response of 4log (RM4log) or higher for one year.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be followed for 2 years, with molecular monitoring, every month in the first&#xD;
      year and then every 2 months. Imatinib will be restarted if the major molecular response&#xD;
      (RM3log) is lost during the study or if the subject withdraw the informed consenting.&#xD;
&#xD;
      The primary objective is to measure the number of subject that sustain the major molecular&#xD;
      response (RM3log or BCR-ABL level below 0.1%) after 2 years of follow-up.&#xD;
&#xD;
      BCR: breakpoint cluster region&#xD;
&#xD;
      ABL: abelson murine leukemia&#xD;
&#xD;
      RM3log: major molecular response, BCR-ABL level below 0.1% (IS)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 15, 2016</start_date>
  <completion_date type="Anticipated">January 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2019</primary_completion_date>
  <phase>N/A</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>single-arm study; all patients will discontinue imatinib (intervention)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects that remain with RM3log after imatinib discontinuation</measure>
    <time_frame>24 months</time_frame>
    <description>Number of subjects that sustain BCR-ABL level below 0,1% after 24 months of follow up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects that recover MR3log after imatinib reintroduction</measure>
    <time_frame>6 months</time_frame>
    <description>In the population that do not sustain BCR-ABL below 0,1% during the study, the time to recover the response after imatinib reintroduction will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of immunological profile of all subjects</measure>
    <time_frame>24 months</time_frame>
    <description>Study of lymphocytes population by flow cytometry, including NK and T population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of imatinib discontinuation</measure>
    <time_frame>24 months</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Leukemia, Myeloid, Chronic-Phase</condition>
  <arm_group>
    <arm_group_label>Discontinuation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will discontinue imatinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>imatinib discontinuation</intervention_name>
    <description>imatinib discontinuation</description>
    <arm_group_label>Discontinuation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic myeloid leukemia chronic-phase, defined by the World Health Organization&#xD;
             criteria&#xD;
&#xD;
          -  Treatment with imatinib for at least 36 months&#xD;
&#xD;
          -  BCR-ABL levels below 0,01% (IS) or MR4log in the last 12 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous allogeneic stem cell transplantation&#xD;
&#xD;
          -  Previous treatment with dasatinib, nilotinib, bosutinib or ponatinib&#xD;
&#xD;
          -  Imatinib dose escalation at any time, due to loss or inadequate response&#xD;
&#xD;
          -  BCR-ABL mutation&#xD;
&#xD;
        IS: International Scale&#xD;
&#xD;
        MR4log: molecular response of 4log or &lt;0,1% (IS)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Centro de Pesquisa Clínica da Hematologia do HCFMUSP</name>
      <address>
        <city>São Paulo</city>
        <state>Sao Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>May 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>March 22, 2018</last_update_submitted>
  <last_update_submitted_qc>March 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2018</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</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Leukemia, Myeloid, Chronic-Phase</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Imatinib Mesylate</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/NCT03239886
org study id: 15418
nct id: NCT03239886
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the proportion of subjects with chronic myeloid leukemia chronic
      phase that sustain major molecular response after imatinib discontinuation. To be eligible
      for this protocol, the subject must have received imatinib as first line regiment for at
      least 3 years with sustained molecular response of 4log (RM4log) or higher for one year.
Patients will be followed for 2 years, with molecular monitoring, every month in the first
      year and then every 2 months. Imatinib will be restarted if the major molecular response
      (RM3log) is lost during the study or if the subject withdraw the informed consenting.

      The primary objective is to measure the number of subject that sustain the major molecular
      response (RM3log or BCR-ABL level below 0.1%) after 2 years of follow-up.

      BCR: breakpoint cluster region

      ABL: abelson murine leukemia

      RM3log: major molecular response, BCR-ABL level below 0.1% (IS)
allocation: N/A
intervention model: Single Group Assignment
intervention model description: single-arm study; all patients will discontinue imatinib (intervention)
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects that remain with RM3log after imatinib discontinuation
time frame: 24 months
description: Number of subjects that sustain BCR-ABL level below 0,1% after 24 months of follow up.
measure: Number of subjects that recover MR3log after imatinib reintroduction
time frame: 6 months
description: In the population that do not sustain BCR-ABL below 0,1% during the study, the time to recover the response after imatinib reintroduction will be measured
measure: Analysis of immunological profile of all subjects
time frame: 24 months
description: Study of lymphocytes population by flow cytometry, including NK and T population
measure: Safety and tolerability of imatinib discontinuation
time frame: 24 months
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
arm group label: Discontinuation
arm group type: Experimental
description: All subjects will discontinue imatinib
intervention type: Other
intervention name: imatinib discontinuation
description: imatinib discontinuation
arm group label: Discontinuation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Leukemia, Myeloid, Chronic-Phase
mesh term: Imatinib Mesylate
sharing ipd: No