<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/NCT04425824</url>
  </required_header>
  <id_info>
    <org_study_id>NCC2244</org_study_id>
    <nct_id>NCT04425824</nct_id>
  </id_info>
  <brief_title>Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma</brief_title>
  <official_title>Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma: An Exploratory Small Sample, Phase II, Single-center Clinical Trail</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</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>
      Exploring the efficacy and safety of Toripalimab with Rituximab for treatment of relapsed&#xD;
      refractory CD20 positive diffuse large B-cell lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal&#xD;
      antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1&#xD;
      (PD-L1) and 2 (PD-L2). Rituximab is an antibody to CD20 molecules. One of the mechanisms of&#xD;
      killing tumor cells is through antibody-dependent cell-mediated cytotoxicity (ADCC). These&#xD;
      two drugs may have a synergistic effect on anti-tumor. The purpose of this study is to&#xD;
      determine whether Toripalimab with Rituximab is effective and safe for treatment of relapsed&#xD;
      refractory CD20 positive diffuse large B-cell lymphoma. This is an exploratory small sample,&#xD;
      phase II, single-center clinical trial, which is going to enroll 20 participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 15, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>Objective Response Rate(ORR)</measure>
    <time_frame>up to 24 months</time_frame>
    <description>From the beginning of treatment, adopt Lugano 2014 evaluation standard, imaging examinations are performed every 2 cycles to assess changes in disease until progression or death</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival(PFS)</measure>
    <time_frame>up to 24 months</time_frame>
    <description>From the date into this study to disease progression or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assessment of the safety events</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Number of subjects experiencing different-grade toxicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the correlation between tumor cell PD-L1 expression intensity and efficacy</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Subjects will be according to the Lugano 2014 criteria assessed with computed tomograph(CT) at screening,after completion of treantment therapy and during the post-treatment follow-up period.Baseline biopsies for immunologic analyses will be obtained from patients. Secondary histologic outcome include percent PD-L1 positive tumor cells by immunohistochemistry.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Analysis of the correlation between the ammount of T cells and NK cells around tumor cells</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Baseline and post-treatment biopsies for immunologic analyses will be obtained from patients.Histologic outcomes include percent and density PD-L1 positive tumor cells, percent and density CD56 postive NK cells, percent and density CD3 positive T cells by immunohistochemistry.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in immune microenviroment at the time of initial diagnosis and relapse</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Immune mincroenviroment to be assessed by analyzing changes in the immune infiltrate in biopsy specimens obtained at initial diagnosis and relapse. Histologic outcome include percent and density PD-L1 positive tumor cells and CD3,CD4,CD8,CD56,CD58,PD-1,β2-MG,CIITA,HLA-DR/DP/DQ positive cells.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Diffuse Large B-cell Lymphoma</condition>
  <condition>Rituximab</condition>
  <condition>Toripalimab</condition>
  <arm_group>
    <arm_group_label>Toripalimab combine with Rituximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental: Toripalimab combine with Rituximab&#xD;
Induction period:&#xD;
Toripalimab 240mg administered intravenously (IV) on Day 1 of each 21-day cycle for 6 cycles.&#xD;
Rituximab 375mg/m² administered intravenously (IV) on Day 1 of each 21-day cycle for 6 cycles.&#xD;
Maintenance:&#xD;
Toripalimab 240mg administered intravenously (IV) and Rituximab 375mg/m² on Day 1 of each 56-day cycle for 6 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab combine with Rituximab</intervention_name>
    <description>Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2).&#xD;
Drug: Rituximab Rituximab is an antibody to CD20 molecules. One of the mechanisms of killing tumor cells is through antibody-dependent cell-mediated cytotoxicity (ADCC).</description>
    <arm_group_label>Toripalimab combine with Rituximab</arm_group_label>
    <other_name>JS001 combine with rituxan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 years old;&#xD;
&#xD;
          2. According to the WHO 2016 classification criteria, the CD20 positive diffuse large&#xD;
             B-cell lymphoma (DLBCL) diagnosed by pathology should include the indicators of&#xD;
             immunohistochemistry: CD10, BCL-2, MUM-1, BCL-6 and C-MYC;&#xD;
&#xD;
          3. Relapsed or refractory DLBCL.Patients younger than 65 years should relapse or progress&#xD;
             after receiving at least second-line treatment, and patients 65 years of age and older&#xD;
             could be intolerant to second-line treatment, and they who relapse or progress after&#xD;
             receiving first-line treatment;&#xD;
&#xD;
          4. There is at least one measurable lesion, defined as measurable dual-diameter,&#xD;
             intra-lymph node lesion, short diameter&gt; 1.5cm, extra-lymph node lesion short&#xD;
             diameter&gt; 1.0cm;&#xD;
&#xD;
          5. Recurrence confirmed by pathological biopsy and CD20 positive;&#xD;
&#xD;
          6. ECOG score 0-2 points;&#xD;
&#xD;
          7. No autoimmune diseases;&#xD;
&#xD;
          8. Blood routine examination meets the following criteria:&#xD;
&#xD;
               1. Neutrophil count ≥ 1.5 x 109 / L,;&#xD;
&#xD;
               2. Platelet ≥ 75 x 109 / L,;&#xD;
&#xD;
               3. Hemoglobin ≥ 10.0 g / dL;&#xD;
&#xD;
          9. The main organ function meets the following criteria:&#xD;
&#xD;
               1. Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 times the upper&#xD;
                  limit of normal value;&#xD;
&#xD;
               2. Bilirubin ≤ 2.0 mg / dL;&#xD;
&#xD;
               3. Creatinine clearance rate ≥ 60 mL / min;&#xD;
&#xD;
         10. Patients must agree to take effective contraceptive measures during the study&#xD;
             according to the investigator's request;&#xD;
&#xD;
         11. Understand and voluntarily sign written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosed as transformed diffuse large B-cell lymphoma;&#xD;
&#xD;
          2. Diagnosed as double-hit diffuse large B-cell lymphoma (DHL);&#xD;
&#xD;
          3. Diagnosed as primary or secondary central nervous system lymphoma;&#xD;
&#xD;
          4. HBV DNA positive or HCV RNA positive patients;&#xD;
&#xD;
          5. Left ventricular ejection fraction &lt;50%;&#xD;
&#xD;
          6. Patients with history of autoimmune diseases, including but not limited to systemic&#xD;
             lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, ankylosing spondylitis&#xD;
&#xD;
          7. Patients are using or have been used immunosuppressive drugs&#xD;
&#xD;
          8. Patients with ≥2 grade peripheral neuropathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Yan Qin, doctor</last_name>
    <phone>13601282738</phone>
    <email>qinyan66@vip.sina.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer Institute/Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Yan Qin, doctor</last_name>
      <phone>13601282738</phone>
      <email>qinyan66@vip.sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 12, 2020</last_update_submitted>
  <last_update_submitted_qc>June 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Shi Yuankai</investigator_full_name>
    <investigator_title>chief physician</investigator_title>
  </responsible_party>
  <keyword>DLBCL</keyword>
  <keyword>CD20</keyword>
  <keyword>Toripalimab</keyword>
  <keyword>Rituximab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</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/NCT04425824
org study id: NCC2244
nct id: NCT04425824
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Exploring the efficacy and safety of Toripalimab with Rituximab for treatment of relapsed
      refractory CD20 positive diffuse large B-cell lymphoma.
Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal
      antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1
      (PD-L1) and 2 (PD-L2). Rituximab is an antibody to CD20 molecules. One of the mechanisms of
      killing tumor cells is through antibody-dependent cell-mediated cytotoxicity (ADCC). These
      two drugs may have a synergistic effect on anti-tumor. The purpose of this study is to
      determine whether Toripalimab with Rituximab is effective and safe for treatment of relapsed
      refractory CD20 positive diffuse large B-cell lymphoma. This is an exploratory small sample,
      phase II, single-center clinical trial, which is going to enroll 20 participants.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate(ORR)
time frame: up to 24 months
description: From the beginning of treatment, adopt Lugano 2014 evaluation standard, imaging examinations are performed every 2 cycles to assess changes in disease until progression or death
measure: Progression Free Survival(PFS)
time frame: up to 24 months
description: From the date into this study to disease progression or death
measure: To assessment of the safety events
time frame: up to 24 months
description: Number of subjects experiencing different-grade toxicity
measure: Assessment of the correlation between tumor cell PD-L1 expression intensity and efficacy
time frame: up to 24 months
description: Subjects will be according to the Lugano 2014 criteria assessed with computed tomograph(CT) at screening,after completion of treantment therapy and during the post-treatment follow-up period.Baseline biopsies for immunologic analyses will be obtained from patients. Secondary histologic outcome include percent PD-L1 positive tumor cells by immunohistochemistry.
measure: Analysis of the correlation between the ammount of T cells and NK cells around tumor cells
time frame: up to 24 months
description: Baseline and post-treatment biopsies for immunologic analyses will be obtained from patients.Histologic outcomes include percent and density PD-L1 positive tumor cells, percent and density CD56 postive NK cells, percent and density CD3 positive T cells by immunohistochemistry.
measure: Change in immune microenviroment at the time of initial diagnosis and relapse
time frame: up to 24 months
description: Immune mincroenviroment to be assessed by analyzing changes in the immune infiltrate in biopsy specimens obtained at initial diagnosis and relapse. Histologic outcome include percent and density PD-L1 positive tumor cells and CD3,CD4,CD8,CD56,CD58,PD-1,β2-MG,CIITA,HLA-DR/DP/DQ positive cells.
arm group label: Toripalimab combine with Rituximab
arm group type: Experimental
description: Experimental: Toripalimab combine with Rituximab
Induction period:
Toripalimab 240mg administered intravenously (IV) on Day 1 of each 21-day cycle for 6 cycles.
Rituximab 375mg/m² administered intravenously (IV) on Day 1 of each 21-day cycle for 6 cycles.
Maintenance:
Toripalimab 240mg administered intravenously (IV) and Rituximab 375mg/m² on Day 1 of each 56-day cycle for 6 cycles.
intervention type: Drug
intervention name: Toripalimab combine with Rituximab
description: Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2).
Drug: Rituximab Rituximab is an antibody to CD20 molecules. One of the mechanisms of killing tumor cells is through antibody-dependent cell-mediated cytotoxicity (ADCC).
arm group label: Toripalimab combine with Rituximab
other name: JS001 combine with rituxan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Yan Qin, doctor
phone: 13601282738
email: qinyan66@vip.sina.com
facility: 
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Shi Yuankai
investigator title: chief physician
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Rituximab