<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/NCT03250962</url>
  </required_header>
  <id_info>
    <org_study_id>CHN-PLAGH-BT-023</org_study_id>
    <nct_id>NCT03250962</nct_id>
  </id_info>
  <brief_title>SHR-1210 Alone or in Combination With Decitabine in Relapsed or Refractory Hodgkin Lymphoma</brief_title>
  <official_title>Anti-PD-1 Antibody SHR-1210 Alone or in Combination With Decitabine in Relapsed or Refractory Hodgkin Lymphoma:an Open-label Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese PLA General 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 is a two-stage, Phase II clinical trial for patients with relapsed or refractory Hodgkin&#xD;
      Lymphoma. The purpose of stage I is to evaluate whether treatment with the study drug&#xD;
      decitabine in combination with SHR-1210 is safe and more effective than treatment with&#xD;
      SHR-1210 alone; and reverse the resistance of anti-PD-1 antibody in patients with HL who had&#xD;
      previously treated with anti-PD-1 monotherapy. If it is deemed that the combination therapy&#xD;
      is more efficacious than SHR-1210 monotherapy (The CR rate of the combination group is at&#xD;
      least 30% higher compared to monotherapy group with a minimal follow-up of 6 months in&#xD;
      predicting 60 subjects naïve to anti-PD-1 antibody who are randomly assigned (2:1) to the&#xD;
      above two groups), the stage II study will be revised to a multicohort,&#xD;
      decitabine-plus-SHR1210 single-arm clinical trial. The primary objective of stage II study is&#xD;
      to evaluate the long-term response duration with decitabine-plus-SHR-1210 in relapsed or&#xD;
      refractory Hodgkin Lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 11, 2017</start_date>
  <completion_date type="Anticipated">March 21, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 21, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>stage I: Number of Subjects with treatment-related adverse events (AEs)</measure>
    <time_frame>2 years</time_frame>
    <description>Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>stage I: CRR assess by investigators per the 2014 Lugano classification</measure>
    <time_frame>3 years</time_frame>
    <description>rate of subjects achieved complete response in all evaluable subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>stage II: duration of CR</measure>
    <time_frame>5 years</time_frame>
    <description>Time measured from the day of first documented CR to the date of first documented progression, or death from any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>stage II: duration of response</measure>
    <time_frame>5 years</time_frame>
    <description>Time measured from the day of first documented PR or CR to the date of first documented progression, or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>stage II: Progression free survival</measure>
    <time_frame>5 years</time_frame>
    <description>Time measured from the day of treatment to the date of first documented progression, or death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">280</enrollment>
  <condition>Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>SHR-1210-plus-Decitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Decitabine 10 mg/day, days 1-5; SHR-1210 200 mg, day 8, every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR-1210</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHR-1210 200 mg, day 1, every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR-1210</intervention_name>
    <description>SHR-1210 is a humanized anti-PD-1 monoclonal antibody.</description>
    <arm_group_label>SHR-1210</arm_group_label>
    <arm_group_label>SHR-1210-plus-Decitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Decitabine</intervention_name>
    <description>Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.</description>
    <arm_group_label>SHR-1210-plus-Decitabine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1 Subjects must have histological confirmation of relapsed or refractory Hodgkin&#xD;
             lymphoma (HL).&#xD;
&#xD;
             2 12 to 75 years of age. 3 ECOG performance of less than 2. 4 Life expectancy of at&#xD;
             least 3 months. 5 Subjects with lymphoma must have at least one measureable lesion &gt;1&#xD;
             cm as defined by lymphoma response criteria.&#xD;
&#xD;
             6 Subjects must have received at least four prior chemotherapy regimen, and must be&#xD;
             off therapy for at least 4 weeks prior to Day 1. Subjects with autologous&#xD;
             hematopoietic stem-cell transplantation are eligible which must be more than 3&#xD;
             months.Subjects with Anti-PD-1 antibody are eligible which must be resistance.&#xD;
&#xD;
             7 Subjects must have adequate marrow, live, renal and heart functions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1 Subjects with any autoimmune disease or history of syndrome that requires&#xD;
             corticosteroids or immunosuppressive medications.&#xD;
&#xD;
             2 Serious uncontrolled medical disorders or active infections, pulmonary infection&#xD;
             especially.&#xD;
&#xD;
             3 Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1&#xD;
             month .&#xD;
&#xD;
             4 Prior organ allograft. 5 Women who are pregnant or breastfeeding. 6 Women with a&#xD;
             positive pregnancy test on enrollment or prior to investigational product&#xD;
             administration.&#xD;
&#xD;
             7 Subjects who are compulsorily detained for treatment of either a psychiatric or&#xD;
             physical (eg, infectious disease) illness.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Biotherapeutic Department of Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100853</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Weidong Han, M.D</last_name>
      <phone>+86-10-66937463</phone>
      <email>hanwdrsw@sina.com</email>
    </contact>
    <contact_backup>
      <last_name>Qingming Yang, M.D</last_name>
      <phone>+86-10-55499341</phone>
      <email>yangqm@medmail.com.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Weidong Han, M.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jing Nie, Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Qingming Yang, M.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yang Liu, M.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Chunmeng Wang, M.S</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wenjing Ku, M.S</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yan Zhang, M.S</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Meixia Chen, M.S</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Qian Mei, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Xiang Li, B.S</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jiejie Liu, B.S</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Liang Dong, B.S</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jie Bai, M.S</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 10, 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 28, 2019</last_update_submitted>
  <last_update_submitted_qc>March 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese PLA General Hospital</investigator_affiliation>
    <investigator_full_name>Han weidong</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Relapsed/Refractory; Hodgkin Lymphoma；Decitabine; SHR-1210</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Decitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Study Protocol</ipd_description>
  </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/NCT03250962
org study id: CHN-PLAGH-BT-023
nct id: NCT03250962
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a two-stage, Phase II clinical trial for patients with relapsed or refractory Hodgkin
      Lymphoma. The purpose of stage I is to evaluate whether treatment with the study drug
      decitabine in combination with SHR-1210 is safe and more effective than treatment with
      SHR-1210 alone; and reverse the resistance of anti-PD-1 antibody in patients with HL who had
      previously treated with anti-PD-1 monotherapy. If it is deemed that the combination therapy
      is more efficacious than SHR-1210 monotherapy (The CR rate of the combination group is at
      least 30% higher compared to monotherapy group with a minimal follow-up of 6 months in
      predicting 60 subjects naïve to anti-PD-1 antibody who are randomly assigned (2:1) to the
      above two groups), the stage II study will be revised to a multicohort,
      decitabine-plus-SHR1210 single-arm clinical trial. The primary objective of stage II study is
      to evaluate the long-term response duration with decitabine-plus-SHR-1210 in relapsed or
      refractory Hodgkin Lymphoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: stage I: Number of Subjects with treatment-related adverse events (AEs)
time frame: 2 years
description: Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.
measure: stage I: CRR assess by investigators per the 2014 Lugano classification
time frame: 3 years
description: rate of subjects achieved complete response in all evaluable subjects
measure: stage II: duration of CR
time frame: 5 years
description: Time measured from the day of first documented CR to the date of first documented progression, or death from any cause.
measure: stage II: duration of response
time frame: 5 years
description: Time measured from the day of first documented PR or CR to the date of first documented progression, or death from any cause.
measure: stage II: Progression free survival
time frame: 5 years
description: Time measured from the day of treatment to the date of first documented progression, or death from any cause.
arm group label: SHR-1210-plus-Decitabine
arm group type: Experimental
description: Decitabine 10 mg/day, days 1-5; SHR-1210 200 mg, day 8, every 3 weeks.
arm group label: SHR-1210
arm group type: Experimental
description: SHR-1210 200 mg, day 1, every 3 weeks.
intervention type: Drug
intervention name: SHR-1210
description: SHR-1210 is a humanized anti-PD-1 monoclonal antibody.
arm group label: SHR-1210
arm group label: SHR-1210-plus-Decitabine
intervention type: Drug
intervention name: Decitabine
description: Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.
arm group label: SHR-1210-plus-Decitabine
criteria: 
gender: All
minimum age: 12 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese PLA General Hospital
investigator full name: Han weidong
investigator title: Principal Investigator
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Decitabine
sharing ipd: No
ipd description: Study Protocol