<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/NCT03241199</url>
  </required_header>
  <id_info>
    <org_study_id>QMH-CML-002</org_study_id>
    <nct_id>NCT03241199</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of Induction-Maintenance Protocol for Patients With Chronic Myelogenous Leukaemia</brief_title>
  <official_title>A Phase II Study to Determine the Efficacy and Safety of Induction-Maintenance Protocol for Patients With Chronic-Phase Chronic Myelogenous Leukaemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</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>
      The purpose of this pilot study is to investigate whether some patients who were started on a&#xD;
      2G-TKI as first-line treatment can be safely switched to imatinib, a first-generation TKI,&#xD;
      while maintaining or even deepening the molecular response as a cost-effective treatment.&#xD;
      Eligible patients will be switched to imatinib 400mg daily, with regular molecular&#xD;
      monitoring.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Imatinib, nilotinib and dasatinib are standard first-line options for newly diagnosed&#xD;
      patients with chronic-phase chronic myeloid leukemia (CML). While nilotinib and dasatinib,&#xD;
      also known as second-generation TKI (2G-TKI), have been shown to result in earlier and deeper&#xD;
      molecular response, they have not been proven superior to imatinib in terms of clinical&#xD;
      outcomes like progression-free survival and overall survival. Moreover, their long-term&#xD;
      safety has been questioned: nilotinib is associated with increased cardiovascular risk while&#xD;
      dasatinib causes pleural effusion in significant proportion of patients and may even lead to&#xD;
      pulmonary hypertension.&#xD;
&#xD;
      The purpose of this pilot study is to investigate whether some patients who were started on a&#xD;
      2G-TKI as first-line treatment can be safely switched to imatinib, a first-generation TKI,&#xD;
      while maintaining or even deepening the molecular response as a cost-effective treatment.&#xD;
      Eligible patients will be switched to imatinib 400mg daily, with regular molecular&#xD;
      monitoring.&#xD;
&#xD;
      In case of molecular progression&#xD;
&#xD;
      The following should be systematically performed:&#xD;
&#xD;
        -  Clinical examination&#xD;
&#xD;
        -  Baseline blood test including complete blood count (CBC), liver and renal function,&#xD;
           lactate dehydrogenase (LDH), urate&#xD;
&#xD;
        -  Restart the original 2G-TKI and in same dose as given before study entry unless&#xD;
           medically indicated to change therapy&#xD;
&#xD;
        -  Screening of breakpoint cluster region- Abelson murine leukemia (BCR-ABL) kinase domain&#xD;
           mutations&#xD;
&#xD;
        -  In the absence of signs of haematological relapse or breakpoint cluster region- Abelson&#xD;
           murine leukemia (BCR-ABL1) ≥ 1% (IS ratio), bone marrow aspiration and cytogenetics are&#xD;
           not routinely performed unless deemed indicated by the physician in charge.&#xD;
&#xD;
      The patient will be followed until major molecular response (MMR) is re-achieved and further&#xD;
      6 months beyond. Date of progression, hematological data at progression (molecular,&#xD;
      cytogenetic, and hematological), and treatment proposed for molecular progression and&#xD;
      response to it (molecular, cytogenetic, hematological) will be collected. Follow-up for&#xD;
      overall survival (OS) and progression-free survival (PFS) will last 2 years since the date of&#xD;
      switch of TKI.&#xD;
&#xD;
      In case of loss of complete hematological response (CHR) or any sign of accelerated or&#xD;
      blastic phase of CML, the patient will be immediately considered as in disease progression&#xD;
      and TKI should be started immediately.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Anticipated">January 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 13, 2020</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>molecular progression-free survival</measure>
    <time_frame>6 months</time_frame>
    <description>Molecular progression-free survival after switch to imatinib at 6 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>molecular progression-free survival</measure>
    <time_frame>12 months</time_frame>
    <description>Molecular progression-free survival after switch to imatinib at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>molecular progression-free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Molecular progression-free survival after switch to imatinib at 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molecular responses</measure>
    <time_frame>12 months</time_frame>
    <description>Molecular responses after switch to imatinib at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molecular responses</measure>
    <time_frame>24 months</time_frame>
    <description>Molecular responses after switch to imatinib at 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of molecular progression on Imatinib</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients who have molecular progression on Imatinib</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of regain MMR after resumption of original TKI and time to recovery of MMR</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients who regain MMR on resumption of their original TKI, and time to recovery of MMR</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Chronic Myeloid Leukemia</condition>
  <condition>Philadelphia Chromosome Positive CML</condition>
  <arm_group>
    <arm_group_label>Imatinib Mesylate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>imatinib 400mg daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Imatinib Mesylate</intervention_name>
    <description>a first-generation tyrosine kinase inhibitors</description>
    <arm_group_label>Imatinib Mesylate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult (aged 18 years or above) patients diagnosed with chronic-phase CML&#xD;
&#xD;
          2. Must have received a 2G-TKI (nilotinib or dasatinib) as first-line therapy for at&#xD;
             least 12 months (Note: Cytoreductive agents, namely hydroxyurea and anagrelide, prior&#xD;
             to the use of TKI are allowed.)&#xD;
&#xD;
          3. In sustained, good molecular response (i.e. molecular response (MR3) or below) for at&#xD;
             least 6 months, as confirmed with at least 2 consecutive quantitative real&#xD;
             time-polymerase chain reaction (RT-PCR) results&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Under 18 years old&#xD;
&#xD;
          2. Adults under law protection or without ability to consent&#xD;
&#xD;
          3. Previous or planned autologous/allogeneic haematopoietic stem cell transplantation&#xD;
&#xD;
          4. Documented kinase domain mutation&#xD;
&#xD;
          5. A change to the current TKI because of unsatisfactory response to a previous TKI&#xD;
             (Note: patients are still considered eligible if the switch in TKI was due to&#xD;
             intolerance or side effects)&#xD;
&#xD;
          6. History of disease progression (accelerated or blast phase)&#xD;
&#xD;
          7. Patients who can speak neither Chinese nor English&#xD;
&#xD;
          8. Any molecular result during the preceding 6 months that is higher than MR3, i.e.&#xD;
             BCR-ABL1/ABL1 ratio &gt;0.1% on IS ratio&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carol Cheung, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Queen Mary Hospital, Hong Kong</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Carol Cheung, MBBS</last_name>
    <phone>852 22553111</phone>
    <phone_ext>3456</phone_ext>
    <email>drcarolcheung@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Crosby Lu, MMedSc</last_name>
    <phone>852 22553111</phone>
    <phone_ext>1654</phone_ext>
    <email>khlu@hku.hk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The University of Hong Kong</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carol Cheung, MBBS</last_name>
      <phone>852 22553111</phone>
      <phone_ext>3456</phone_ext>
      <email>drcarolcheung@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Crosby Lu, MMedSc</last_name>
      <phone>852 22553111</phone>
      <phone_ext>1654</phone_ext>
      <email>khlu@hku.hk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>August 7, 2017</last_update_submitted>
  <last_update_submitted_qc>August 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Professor Yok-lam Kwong</investigator_full_name>
    <investigator_title>Chair 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, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Philadelphia Chromosome</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>Undecided</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/NCT03241199
org study id: QMH-CML-002
nct id: NCT03241199
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this pilot study is to investigate whether some patients who were started on a
      2G-TKI as first-line treatment can be safely switched to imatinib, a first-generation TKI,
      while maintaining or even deepening the molecular response as a cost-effective treatment.
      Eligible patients will be switched to imatinib 400mg daily, with regular molecular
      monitoring.
Imatinib, nilotinib and dasatinib are standard first-line options for newly diagnosed
      patients with chronic-phase chronic myeloid leukemia (CML). While nilotinib and dasatinib,
      also known as second-generation TKI (2G-TKI), have been shown to result in earlier and deeper
      molecular response, they have not been proven superior to imatinib in terms of clinical
      outcomes like progression-free survival and overall survival. Moreover, their long-term
      safety has been questioned: nilotinib is associated with increased cardiovascular risk while
      dasatinib causes pleural effusion in significant proportion of patients and may even lead to
      pulmonary hypertension.

      The purpose of this pilot study is to investigate whether some patients who were started on a
      2G-TKI as first-line treatment can be safely switched to imatinib, a first-generation TKI,
      while maintaining or even deepening the molecular response as a cost-effective treatment.
      Eligible patients will be switched to imatinib 400mg daily, with regular molecular
      monitoring.

      In case of molecular progression

      The following should be systematically performed:

        -  Clinical examination

        -  Baseline blood test including complete blood count (CBC), liver and renal function,
           lactate dehydrogenase (LDH), urate

        -  Restart the original 2G-TKI and in same dose as given before study entry unless
           medically indicated to change therapy

        -  Screening of breakpoint cluster region- Abelson murine leukemia (BCR-ABL) kinase domain
           mutations

        -  In the absence of signs of haematological relapse or breakpoint cluster region- Abelson
           murine leukemia (BCR-ABL1) ≥ 1% (IS ratio), bone marrow aspiration and cytogenetics are
           not routinely performed unless deemed indicated by the physician in charge.

      The patient will be followed until major molecular response (MMR) is re-achieved and further
      6 months beyond. Date of progression, hematological data at progression (molecular,
      cytogenetic, and hematological), and treatment proposed for molecular progression and
      response to it (molecular, cytogenetic, hematological) will be collected. Follow-up for
      overall survival (OS) and progression-free survival (PFS) will last 2 years since the date of
      switch of TKI.

      In case of loss of complete hematological response (CHR) or any sign of accelerated or
      blastic phase of CML, the patient will be immediately considered as in disease progression
      and TKI should be started immediately.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: molecular progression-free survival
time frame: 6 months
description: Molecular progression-free survival after switch to imatinib at 6 months
measure: molecular progression-free survival
time frame: 12 months
description: Molecular progression-free survival after switch to imatinib at 12 months
measure: molecular progression-free survival
time frame: 24 months
description: Molecular progression-free survival after switch to imatinib at 24 months
measure: Molecular responses
time frame: 12 months
description: Molecular responses after switch to imatinib at 12 months
measure: Molecular responses
time frame: 24 months
description: Molecular responses after switch to imatinib at 24 months
measure: Rate of molecular progression on Imatinib
time frame: 24 months
description: Number of patients who have molecular progression on Imatinib
measure: Rate of regain MMR after resumption of original TKI and time to recovery of MMR
time frame: 24 months
description: Number of patients who regain MMR on resumption of their original TKI, and time to recovery of MMR
arm group label: Imatinib Mesylate
arm group type: Experimental
description: imatinib 400mg daily
intervention type: Drug
intervention name: Imatinib Mesylate
description: a first-generation tyrosine kinase inhibitors
arm group label: Imatinib Mesylate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carol Cheung, MBBS
role: Principal Investigator
affiliation: Queen Mary Hospital, Hong Kong
last name: Carol Cheung, MBBS
phone: 852 22553111
phone ext: 3456
email: drcarolcheung@gmail.com
last name: Crosby Lu, MMedSc
phone: 852 22553111
phone ext: 1654
email: khlu@hku.hk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Professor Yok-lam Kwong
investigator title: Chair Professor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Philadelphia Chromosome
mesh term: Imatinib Mesylate
sharing ipd: Undecided