<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/NCT03251352</url>
  </required_header>
  <id_info>
    <org_study_id>201733572018022</org_study_id>
    <nct_id>NCT03251352</nct_id>
  </id_info>
  <brief_title>TKI Discontinuation in CML Patients of China</brief_title>
  <acronym>TFR_china</acronym>
  <official_title>Tyrosine Kinase Inhibitor Discontinuation in Adults Patients With Chronic Myeloid Leukemia in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shenzhen Second People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shenzhen Second People's Hospital</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>
      The primary objective of this study is to describe the maintenance of the molecular remission&#xD;
      after tyrosine kinase inhibitor (TKI) disconnection in chronic myeloid leukaemia (CML)&#xD;
      patients in China in the real-world clinical practice setting. This is a post-marketing,&#xD;
      non-interventional, single-arm, prospective registry study in adult patients with chronic&#xD;
      phase (CP) and accelerated phase (AP) in China. Patients will be recruited consecutively from&#xD;
      the study sites during the enrollment period. The enrolled patients will be undertaking TKI&#xD;
      discontinuation under the conditions of informed consent and frequent monitoring according to&#xD;
      the clinical guideline.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tyrosine kinase inhibitors (TKIs) are the standard of care for patients with chronic myeloid&#xD;
      leukaemia (CML) in chronic phase. Imatinib, the first ATP competitive TKI, received approval&#xD;
      for use based on a dramatic and durable survival benefit. Other TKIs, the second generation&#xD;
      compounds dasatinib, nilotinib and bosutinib and the third generation drug ponatinib, were&#xD;
      designed and tested for a greater target-specific potency. With the development of these&#xD;
      effective TKI treatments, CML disease burden can be reduced to minimal levels, and CML&#xD;
      patients can have a life expectancy similar to that of the general population. Although TKI&#xD;
      treatment may result in a deep, stable molecular remission, CML treatment guidelines&#xD;
      recommend that patients continue TKI treatment indefinitely. However, Chronic TKI therapy can&#xD;
      cause drug-related adverse reactions and constitute financial difficulties, which can result&#xD;
      in decreased adherence to therapy. Therefore, the concept of a lifelong therapy with TKIs has&#xD;
      thus been challenged and treatment-free remission (TFR) strategies will soon integrate&#xD;
      clinical practice.TFR can be defined as the ability to maintain molecular remission without&#xD;
      taking any TKI therapy. Studies have demonstrated the feasibility of successful TFR. In the&#xD;
      STIM and TWISTER trials, imatinib discontinuation was proposed providing that patients had&#xD;
      achieved deep molecular response for a certain period. The 2-year probability to maintain&#xD;
      such deep molecular response levels without any TKI therapy was 38% in STIM and 47% in&#xD;
      TWISTER. Subsequently, several studies were conducted and confirmed that imatinib-free&#xD;
      remission was possible. Discontinuation of new generation TKIs was also investigated and&#xD;
      indicated that dasatinib or nilotinib may promote access to TFR strategies as compared to&#xD;
      imatinib. TFR is on the way to become an important goal in clinical practice, implicating an&#xD;
      alternation in CML management guidelines in the near future.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Anticipated">October 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Molecular Remission Rate</measure>
    <time_frame>at 12 months</time_frame>
    <description>The molecular remission rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Incidence of Treatment-free related Adverse Events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>CML molecular recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QoL</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>EROTC-QLQ-C30 and EROTC-QLQ-CML-24</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">98</enrollment>
  <condition>Leukemia</condition>
  <condition>Myelogenous</condition>
  <condition>Chronic</condition>
  <condition>BCR-ABL (Breakpoint Cluster Region-abelson Murine Leukemia)</condition>
  <condition>Positive</condition>
  <arm_group>
    <arm_group_label>TKI Discontinuation Group</arm_group_label>
    <description>The enrolled patients will be undertaking TKI discontinuation under the conditions of informed consent and frequent monitoring according to the clinical guideline.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The targeted population is CML patients under TKI treatment in China.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults with CML-CP/AP and willingness of TKI discontinuation;&#xD;
&#xD;
          -  With ≥ 5 years frontline imatinib, reached MMR (major molecular response) in 2 years,&#xD;
             with ≥ 2 years MR (molecular response) 4.5;&#xD;
&#xD;
          -  Reached MMR with frontline imatinib, with ≥ 2 years nilotinib, with ≥ 1 year MR4.5;&#xD;
&#xD;
          -  Failure with frontline imatinib, reached MMR in 1 year with nilotinib, with ≥ 2 years&#xD;
             MR4.5;&#xD;
&#xD;
          -  With ≥ 3 years frontline imatinib, reached MMR in 1 year, with ≥ 2 years MR4.5.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with CML-BP before TKI treatment;&#xD;
&#xD;
          -  With a TKI discontinuation of over 30 days in the first year;&#xD;
&#xD;
          -  With a TKI discontinuation of over 30days on average annually;&#xD;
&#xD;
          -  Reduced the dosage of TKI treatment without instructions;&#xD;
&#xD;
          -  Transferred to the second-generation TKIs after resistance to imatinib.&#xD;
&#xD;
          -  Under the treatment of stem cells transplantation&#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>Shenzhen Second People's Hospital</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <zip>518035</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xin Du, MD</last_name>
      <phone>075583366388</phone>
      <phone_ext>8196</phone_ext>
      <email>duxingz@medmail.com.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>May 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>March 15, 2022</last_update_submitted>
  <last_update_submitted_qc>March 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TKI, CML, discontinuation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</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/NCT03251352
org study id: 201733572018022
nct id: NCT03251352
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to describe the maintenance of the molecular remission
      after tyrosine kinase inhibitor (TKI) disconnection in chronic myeloid leukaemia (CML)
      patients in China in the real-world clinical practice setting. This is a post-marketing,
      non-interventional, single-arm, prospective registry study in adult patients with chronic
      phase (CP) and accelerated phase (AP) in China. Patients will be recruited consecutively from
      the study sites during the enrollment period. The enrolled patients will be undertaking TKI
      discontinuation under the conditions of informed consent and frequent monitoring according to
      the clinical guideline.
Tyrosine kinase inhibitors (TKIs) are the standard of care for patients with chronic myeloid
      leukaemia (CML) in chronic phase. Imatinib, the first ATP competitive TKI, received approval
      for use based on a dramatic and durable survival benefit. Other TKIs, the second generation
      compounds dasatinib, nilotinib and bosutinib and the third generation drug ponatinib, were
      designed and tested for a greater target-specific potency. With the development of these
      effective TKI treatments, CML disease burden can be reduced to minimal levels, and CML
      patients can have a life expectancy similar to that of the general population. Although TKI
      treatment may result in a deep, stable molecular remission, CML treatment guidelines
      recommend that patients continue TKI treatment indefinitely. However, Chronic TKI therapy can
      cause drug-related adverse reactions and constitute financial difficulties, which can result
      in decreased adherence to therapy. Therefore, the concept of a lifelong therapy with TKIs has
      thus been challenged and treatment-free remission (TFR) strategies will soon integrate
      clinical practice.TFR can be defined as the ability to maintain molecular remission without
      taking any TKI therapy. Studies have demonstrated the feasibility of successful TFR. In the
      STIM and TWISTER trials, imatinib discontinuation was proposed providing that patients had
      achieved deep molecular response for a certain period. The 2-year probability to maintain
      such deep molecular response levels without any TKI therapy was 38% in STIM and 47% in
      TWISTER. Subsequently, several studies were conducted and confirmed that imatinib-free
      remission was possible. Discontinuation of new generation TKIs was also investigated and
      indicated that dasatinib or nilotinib may promote access to TFR strategies as compared to
      imatinib. TFR is on the way to become an important goal in clinical practice, implicating an
      alternation in CML management guidelines in the near future.
observational model: Cohort
time perspective: Prospective
measure: Molecular Remission Rate
time frame: at 12 months
description: The molecular remission rate
measure: Adverse Events
time frame: through study completion, an average of 1 year
description: Incidence of Treatment-free related Adverse Events
measure: Recurrence
time frame: through study completion, an average of 1 year
description: CML molecular recurrence
measure: QoL
time frame: through study completion, an average of 1 year
description: EROTC-QLQ-C30 and EROTC-QLQ-CML-24
arm group label: TKI Discontinuation Group
description: The enrolled patients will be undertaking TKI discontinuation under the conditions of informed consent and frequent monitoring according to the clinical guideline.
whole blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
sharing ipd: No