<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/NCT04480125</url>
  </required_header>
  <id_info>
    <org_study_id>RJ-PTCL-2</org_study_id>
    <nct_id>NCT04480125</nct_id>
  </id_info>
  <brief_title>Azacitidine Combined With Chidamide in the Treatment of Newly Diagnosed PTCL Unfit for Conventional Chemotherapy</brief_title>
  <official_title>The Efficacy and Safety of Azacitidine in Combination With Chidamide in the Treatment of Newly Diagnosed Peripheral T-Cell Lymphoma Unfit for Conventional Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ruijin Hospital</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>
      This prospective, open-label, single-arm study will evaluate the efficacy and safety of&#xD;
      azacitidine in combination with chidamide in treatment of newly diagnosed peripheral T-cell&#xD;
      lymphoma unfit for conventional chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Peripheral T-cell lymphoma (PTCL is a distinct and heterogeneous histopathologic subtype of&#xD;
      non-Hodgkin lymphoma (NHL), accounting for ~10%. CHOP regimen has been widely used in PTCL&#xD;
      patients even with unfavourable prognosis, with 5-year overall survival rate of 38.5%.&#xD;
      Elderly patients seldom benefit from conventional CHOP regimen. A study showed that CR rate&#xD;
      was only 18.1% in elderly patients (median age of 80 years old, ranging from 56 to 93 years&#xD;
      old).&#xD;
&#xD;
      Azacitidine combined with romidepsin has been proved efficient in relasped or refractory&#xD;
      PTCL, with CR rate of 55%. This prospective, open-label, single-arm study will evaluate the&#xD;
      efficacy and safety of azacitidine in combination with Chidamide in treatment of newly&#xD;
      diagnosed peripheral T-cell lymphoma unfit for conventional chemotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 20, 2020</start_date>
  <completion_date type="Anticipated">June 20, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 20, 2022</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>Complete response rate</measure>
    <time_frame>At the end of Cycle 6 (each cycle is 21 days)</time_frame>
    <description>Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>At the end of Cycle 6 (each cycle is 21 days)</time_frame>
    <description>Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Baseline up to data cut-off (up to approximately 4 years)</time_frame>
    <description>Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Baseline up to data cut-off (up to approximately 4 years)</time_frame>
    <description>Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Baseline up to data cut-off (up to approximately 4 years)</time_frame>
    <description>Time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with PET-CT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment related mortality</measure>
    <time_frame>Baseline up to data cut-off (up to approximately 4 years)</time_frame>
    <description>Percentage of death related with treatment on the basis of investigator assessments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE</measure>
    <time_frame>Baseline up to data cut-off (up to approximately 4 years)</time_frame>
    <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores</measure>
    <time_frame>: Baseline (pre-dose [Hour 0] on Cycle1 Day1), Cycle3 Day 1, end of treatment (up to Month 6), every 3 months 1st year, every 6 months 2nd year, and 12 months thereafter up to data cut-off, up to approximately 4 years (cycle length = 21 days)</time_frame>
    <description>The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Circulating free Deoxyribonucleic Acid (cfDNA) monitoring</measure>
    <time_frame>Baseline up to data cut-off (up to approximately 4 years)</time_frame>
    <description>CfDNA in peripheral blood assessed by local lab</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory biomarker analysis</measure>
    <time_frame>Baseline up to data cut-off (up to approximately 4 years)</time_frame>
    <description>Exploratory biomarker to predict treatment response and survival</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">28</enrollment>
  <condition>Peripheral T-cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Aza+Chida</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Azacitidine ivgtt D1-7 Chindamide 30mg,PO,twice a week Every 21 days for total 6 courses</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azacitidine</intervention_name>
    <description>100mg D1-7</description>
    <arm_group_label>Aza+Chida</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chidamide</intervention_name>
    <description>30mg BIW PO</description>
    <arm_group_label>Aza+Chida</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed peripheral T-cell lymphoma based on 2016 WHO classification&#xD;
&#xD;
          -  Treatment naive&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Unfit for converntional chemotherapy meeting criteria as following but not limited to:&#xD;
             age ≥75, ECOG &gt;2，ADL&lt;100 or CCI&gt;1.&#xD;
&#xD;
          -  Must has measurable lesion in CT or PET-CT prior to treatment&#xD;
&#xD;
          -  Expected lifetime ≥ 3 months&#xD;
&#xD;
          -  Informed consented&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has accepted localized or systemic anti-lymphoma treatment&#xD;
&#xD;
          -  Has accepted autologous Stem cell transplantation before&#xD;
&#xD;
          -  History of malignancy except for basal cell or squamous cell carcinoma of the skin or&#xD;
             carcinoma in situ of the cervix prior to study treatment&#xD;
&#xD;
          -  Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious&#xD;
             disease&#xD;
&#xD;
          -  Primary CNS lymphoma&#xD;
&#xD;
          -  Left EF≤ 50%&#xD;
&#xD;
          -  Lab at enrollment (Unless caused by lymphoma): Neutrophile&lt;1.5*10^9/ L&#xD;
             ;Platelet&lt;75*10^9/L; ALT or AST &gt;2*ULN; Creatinine&gt;1.5*ULN&#xD;
&#xD;
          -  Other uncontrollable medical condition that may that may interfere the participation&#xD;
             of the study&#xD;
&#xD;
          -  Not able to comply to the protocol for mental or other unknown reasons&#xD;
&#xD;
          -  Patients with mentally disorders or other reasons unable to fully comply with the&#xD;
             study protocol&#xD;
&#xD;
          -  Pregnant or lactation&#xD;
&#xD;
          -  HIV infection&#xD;
&#xD;
          -  HBV-DNA and HCV-RNA undectable.&#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>Weili Zhao</last_name>
    <role>Study Chair</role>
    <affiliation>Ruijin Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Weili Zhao, PhD，MD</last_name>
    <phone>+862164370045</phone>
    <email>zwl_trial@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pengpeng Xu, PhD，MD</last_name>
    <phone>+862164370045</phone>
    <email>pengpeng_xu@126.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai Ruijin Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Weili Zhao, M.D. and Ph.D</last_name>
      <phone>021-64370045</phone>
      <email>zwl_trial@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 19, 2020</study_first_submitted>
  <study_first_submitted_qc>July 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>April 19, 2022</last_update_submitted>
  <last_update_submitted_qc>April 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ruijin Hospital</investigator_affiliation>
    <investigator_full_name>Zhao Weili</investigator_full_name>
    <investigator_title>First Deputy Director，Hematology Department</investigator_title>
  </responsible_party>
  <keyword>Peripheral T-cell lymphoma</keyword>
  <keyword>Targeted therapy</keyword>
  <keyword>Chemo-free therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azacitidine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04480125
org study id: RJ-PTCL-2
nct id: NCT04480125
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This prospective, open-label, single-arm study will evaluate the efficacy and safety of
      azacitidine in combination with chidamide in treatment of newly diagnosed peripheral T-cell
      lymphoma unfit for conventional chemotherapy.
Peripheral T-cell lymphoma (PTCL is a distinct and heterogeneous histopathologic subtype of
      non-Hodgkin lymphoma (NHL), accounting for ~10%. CHOP regimen has been widely used in PTCL
      patients even with unfavourable prognosis, with 5-year overall survival rate of 38.5%.
      Elderly patients seldom benefit from conventional CHOP regimen. A study showed that CR rate
      was only 18.1% in elderly patients (median age of 80 years old, ranging from 56 to 93 years
      old).

      Azacitidine combined with romidepsin has been proved efficient in relasped or refractory
      PTCL, with CR rate of 55%. This prospective, open-label, single-arm study will evaluate the
      efficacy and safety of azacitidine in combination with Chidamide in treatment of newly
      diagnosed peripheral T-cell lymphoma unfit for conventional chemotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete response rate
time frame: At the end of Cycle 6 (each cycle is 21 days)
description: Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria
measure: Overall response rate
time frame: At the end of Cycle 6 (each cycle is 21 days)
description: Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria
measure: Progression free survival
time frame: Baseline up to data cut-off (up to approximately 4 years)
description: Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.
measure: Overall survival
time frame: Baseline up to data cut-off (up to approximately 4 years)
description: Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.
measure: Duration of response
time frame: Baseline up to data cut-off (up to approximately 4 years)
description: Time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with PET-CT.
measure: Treatment related mortality
time frame: Baseline up to data cut-off (up to approximately 4 years)
description: Percentage of death related with treatment on the basis of investigator assessments
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE
time frame: Baseline up to data cut-off (up to approximately 4 years)
description: An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores
time frame: : Baseline (pre-dose [Hour 0] on Cycle1 Day1), Cycle3 Day 1, end of treatment (up to Month 6), every 3 months 1st year, every 6 months 2nd year, and 12 months thereafter up to data cut-off, up to approximately 4 years (cycle length = 21 days)
description: The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.
measure: Circulating free Deoxyribonucleic Acid (cfDNA) monitoring
time frame: Baseline up to data cut-off (up to approximately 4 years)
description: CfDNA in peripheral blood assessed by local lab
measure: Exploratory biomarker analysis
time frame: Baseline up to data cut-off (up to approximately 4 years)
description: Exploratory biomarker to predict treatment response and survival
arm group label: Aza+Chida
arm group type: Experimental
description: Azacitidine ivgtt D1-7 Chindamide 30mg,PO,twice a week Every 21 days for total 6 courses
intervention type: Drug
intervention name: Azacitidine
description: 100mg D1-7
arm group label: Aza+Chida
intervention type: Drug
intervention name: Chidamide
description: 30mg BIW PO
arm group label: Aza+Chida
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Weili Zhao
role: Study Chair
affiliation: Ruijin Hospital
last name: Weili Zhao, PhD，MD
phone: +862164370045
email: zwl_trial@163.com
last name: Pengpeng Xu, PhD，MD
phone: +862164370045
email: pengpeng_xu@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Ruijin Hospital
investigator full name: Zhao Weili
investigator title: First Deputy Director，Hematology Department
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Azacitidine