<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/NCT03030001</url>
  </required_header>
  <id_info>
    <org_study_id>H2017-01-P01</org_study_id>
    <nct_id>NCT03030001</nct_id>
  </id_info>
  <brief_title>PD-1 Antibody Expressing CAR T Cells for Mesothelin Positive Advanced Malignancies</brief_title>
  <official_title>PD-1 Antibody Expressing Chimeric Antigen Receptor T Cells for Mesothelin Positive Advanced Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ningbo Cancer Hospital</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ningbo Cancer 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 single-arm, open-label, one center, dose escalation clinical study, to determine&#xD;
      the safety and efficacy of infusion of autologous T cells engineered to express immune&#xD;
      checkpoint antibody and chimeric antigen receptor targeting mesothelin in adult patients with&#xD;
      mesothelin positive, recurrent or refractory malignant tumors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">February 15, 2017</start_date>
  <completion_date type="Anticipated">February 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2018</primary_completion_date>
  <phase>Phase 1/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>Safety of infusion of autologous mesothelin specific CAR T cells</measure>
    <time_frame>2 years</time_frame>
    <description>Safety of infusion of autologous mesothelin specific CAR T cells with PD-1 antibody expressing in patients with relapsed or refractory advanced solid malignancies using the NCI CTCAE V4.0 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the response evaluation criteria of solid tumor</measure>
    <time_frame>2 years</time_frame>
    <description>Defined as the overall response rate (ORR), the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on the response evaluation criteria in solid tumor version 1.1 (RECIST1.1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>progression free survival</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change of life quality after treatment</measure>
    <time_frame>2 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>proliferation and persistence of mesothelin specific CAR T cells in patients after treatment</measure>
    <time_frame>6 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>expression of PD-1 antibody in patients after treatment</measure>
    <time_frame>6 months</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Solid Tumor, Adult</condition>
  <condition>Advanced Cancer</condition>
  <arm_group>
    <arm_group_label>PD-1 antibody expressing CAR-T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PD-1 antibody expressing mesothelin specific CAR-T cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PD-1 antibody expressing mesothelin specific CAR-T cells</intervention_name>
    <description>Patients will receive an IV infusion of PD-1 antibody expressing mesothelin specific CAR engineered peripheral blood leukocyte. On day 21, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.</description>
    <arm_group_label>PD-1 antibody expressing CAR-T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Relapsed or refractory advanced solid malignancies.&#xD;
&#xD;
          -  2. Progressive disease and no response to current therapy.&#xD;
&#xD;
          -  3. Patients must have previously received at least one standard therapy for their&#xD;
             cancer (if available) and have been either non-responders (progressive disease) or&#xD;
             have recurred. And patients are willing to attend the clinical trial.&#xD;
&#xD;
          -  4. Gender unlimited, age from 18 years to 80 years.&#xD;
&#xD;
          -  5. Life expectancy≥6 months.&#xD;
&#xD;
          -  6. ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.&#xD;
&#xD;
          -  7. Adequate venous access for apheresis, and no other contraindications for&#xD;
             leukapheresis ; Peripheral venous access ；no contraindication of lymphocyte&#xD;
             separation.&#xD;
&#xD;
          -  8. IHC( immuno-histochemistry) result of tumor tissue： mesothelin positive for&#xD;
             ：frequency≥2，intensity≥2 +. The percentage of tumor cell nuclei stained (0, no&#xD;
             staining; 1, ≤10%; 2, 10-50% and 3, &gt;50%) and the staining intensity (ranging from 0&#xD;
             to 3+).&#xD;
&#xD;
          -  9. Adequate hepatic function, renal function and bone marrow&#xD;
             function：WBC≥3.0×109/L,PLT≥60×109/L,HGB≥85g/L,LY≥0.7×109/L; Alanine&#xD;
             aminotransferase/Aspartate transaminase(ALT/AST) 2.5 times the upper limit of the&#xD;
             normal value, total bilirubin(TBiL) 1times the upper limit of the normal value, Serum&#xD;
             creatinine1.5 times the upper limit of the normal value.&#xD;
&#xD;
          -  10. Willing and able to understand and sign the Informed Consent Document.&#xD;
&#xD;
          -  11. Women of child-bearing age must have evidence of negative pregnancy test. Patients&#xD;
             must be willing to practice birth control during and for four months following&#xD;
             treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Life expectancy6 months.&#xD;
&#xD;
          -  2. Patients with uncontrolled active infection will be excluded.&#xD;
&#xD;
          -  3. Patients with severe heart and lung dysfunction; uncontrolled hypertension,&#xD;
             unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina,&#xD;
             decompensated congestive heart failure (&gt; New York Heart Association Class II), or&#xD;
             myocardial infarction within 6 months of study will be excluded; aberrant pulmonary&#xD;
             function testing: with a forced expiratory volume (FEV) of &lt;30%(predicted), diffusion&#xD;
             capacity of the lung for carbon monoxide (DLCO) (corrected) &lt;30% and oxyhemoglobin&#xD;
             saturation90% will be excluded.&#xD;
&#xD;
          -  4. Patients with severe liver and kidney dysfunction or chronic diseases of important&#xD;
             organs will be excluded.&#xD;
&#xD;
          -  5. Patients with active autoimmune disease requiring immunosuppressive therapy will be&#xD;
             excluded.&#xD;
&#xD;
          -  6. Patients requiring corticosteroids (other than inhaled) will be excluded.&#xD;
&#xD;
          -  7. Patients with other severe diseases or situations improper for the research will be&#xD;
             excluded, including neurologic disease, mental disease, immune disease, metabolic&#xD;
             disease, and contagious disease.&#xD;
&#xD;
          -  8. Pregnant and/or lactating women will be excluded.&#xD;
&#xD;
          -  9. Patients who have had other bio-therapy in the past 4 weeks.&#xD;
&#xD;
          -  10. Patients who are participating or participated any other clinical trials in latest&#xD;
             30 days will be excluded.&#xD;
&#xD;
          -  11. Patients with the subject suffering disease affects the understanding of informed&#xD;
             consent or complying with study protocol will be excluded.&#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_official>
    <last_name>Qijun Qian, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Shanghai Cell Therapy Engineering Research Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Huajun Jin, PhD</last_name>
    <phone>86-13162257545</phone>
    <email>hj_jin@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ningbo No.5 Hospital (Ningbo Cancer Hospital)</name>
      <address>
        <city>Ningbo</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bi Wan</last_name>
      <phone>86-13310088259</phone>
      <email>biwang0218@126.com</email>
    </contact>
    <contact_backup>
      <last_name>Jiangtao Wang</last_name>
      <phone>86-15888102792</phone>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>January 20, 2017</last_update_submitted>
  <last_update_submitted_qc>January 20, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>mesothelin</keyword>
  <keyword>PD-1</keyword>
  <keyword>CAR T</keyword>
  <keyword>solid tumor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</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/NCT03030001
org study id: H2017-01-P01
nct id: NCT03030001
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a single-arm, open-label, one center, dose escalation clinical study, to determine
      the safety and efficacy of infusion of autologous T cells engineered to express immune
      checkpoint antibody and chimeric antigen receptor targeting mesothelin in adult patients with
      mesothelin positive, recurrent or refractory malignant tumors.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of infusion of autologous mesothelin specific CAR T cells
time frame: 2 years
description: Safety of infusion of autologous mesothelin specific CAR T cells with PD-1 antibody expressing in patients with relapsed or refractory advanced solid malignancies using the NCI CTCAE V4.0 criteria
measure: the response evaluation criteria of solid tumor
time frame: 2 years
description: Defined as the overall response rate (ORR), the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on the response evaluation criteria in solid tumor version 1.1 (RECIST1.1).
measure: progression free survival
time frame: 1 year
measure: overall survival
time frame: 2 years
measure: Change of life quality after treatment
time frame: 2 years
measure: proliferation and persistence of mesothelin specific CAR T cells in patients after treatment
time frame: 6 months
measure: expression of PD-1 antibody in patients after treatment
time frame: 6 months
arm group label: PD-1 antibody expressing CAR-T cells
arm group type: Experimental
description: PD-1 antibody expressing mesothelin specific CAR-T cells
intervention type: Biological
intervention name: PD-1 antibody expressing mesothelin specific CAR-T cells
description: Patients will receive an IV infusion of PD-1 antibody expressing mesothelin specific CAR engineered peripheral blood leukocyte. On day 21, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
arm group label: PD-1 antibody expressing CAR-T cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Qijun Qian, PhD
role: Study Chair
affiliation: Shanghai Cell Therapy Engineering Research Institute
last name: Huajun Jin, PhD
phone: 86-13162257545
email: hj_jin@126.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Antibodies
sharing ipd: Undecided