<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/NCT03814447</url>
  </required_header>
  <id_info>
    <org_study_id>MESO-CART</org_study_id>
    <nct_id>NCT03814447</nct_id>
  </id_info>
  <brief_title>The Fourth Generation CART-cell Therapy for Refractory-Relapsed Ovarian Cancer</brief_title>
  <official_title>The Clinical Research of Fourth Generation CART-cell Therapy in Refractory-Relapsed Ovarian Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai 6th People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hrain Biotechnology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai 6th People's 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>
      The goal of this clinical trial is to study the safety and feasibility of anti- Mesothelin&#xD;
      Chimeric Antigen Receptor T-Cell (MESO CAR-T cells) therapy for Refractory-Relapsed Ovarian&#xD;
      Cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
      1. To determine the safety and feasibility of anti- MESO CAR-T cells therapy for&#xD;
      Refractory-Relapsed Ovarian Cancer&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        1. To access the efficacy of anti- MESO CAR-T cells in patients with ovarian cancer.&#xD;
&#xD;
        2. To determine in vivo dynamics and persistency of anti- MESO CAR-T cells&#xD;
&#xD;
        3. To assess the quality of life in patients with ovarian cancer after treatment with anti-&#xD;
           MESO CAR-T cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 16, 2019</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">January 2023</primary_completion_date>
  <phase>Early Phase 1</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>Adverse events (AEs) and Serious adverse event (SAEs)</measure>
    <time_frame>1 year post infusion</time_frame>
    <description>Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.03</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>30 days post infusion</time_frame>
    <description>the highest concentration (Cmax) of anti-human MESO T cells in the peripheral blood after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>30 days post infusion</time_frame>
    <description>the time to reach the highest concentration (Tmax) of anti-human MESO T cells in the peripheral blood after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-30d)</measure>
    <time_frame>30 days post infusion</time_frame>
    <description>the area under the curve of 30 days of anti-human MESO T cells in the peripheral blood after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Mesothelin-positive T cells in circulation</measure>
    <time_frame>90 days post infusion</time_frame>
    <description>Duration of Mesothelin-positive T cells in circulation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>3 months post infusion</time_frame>
    <description>Overall response rate after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>1 year post infusion</time_frame>
    <description>Progress Free Survival after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC Quality-of-Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL) of patients after administration</measure>
    <time_frame>1 year post infusion</time_frame>
    <description>This QLQ-C15-PAL score consists of 15 questions; two multi-item functional scales (physical and emotional functioning), two multi-item symptom scales (fatigue and pain) together with five single-item symptom scales (nausea/vomiting, dyspnea, insomnia, appetite loss, constipation) and one final question referring to overall QOL. The physical functioning scale is based on three questions regarding walking, activities of daily living and time spent in bed or in a chair. The emotional functioning scale is based on two questions that ask about feeling tense or depressed. Patients rated each question on a Likert scale from 1 (not at all) to 4 (very much), with the exception of overall QOL, which was rated from 1 (very poor) to 7 (excellent)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>anti- MESO CAR-T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects in this arm will receive Cyclophosphamide 300mg/m2/d and Fludarabine 30mg/m2/d d-4~-2. Then anti- MESO CAR-T cells will be injected by a dose of 5×106/kg once at d1(rang from d1-3).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>anti- MESO CAR-T cells</intervention_name>
    <description>Autologous genetically modified anti- MESO CAR transduced T cells</description>
    <arm_group_label>anti- MESO CAR-T cells</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>Dose: 30mg/m2/d</description>
    <arm_group_label>anti- MESO CAR-T cells</arm_group_label>
    <other_name>FA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Dose: 300mg/m2/d</description>
    <arm_group_label>anti- MESO CAR-T cells</arm_group_label>
    <other_name>CTX</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histopathologically confirmed ovarian cancer;&#xD;
&#xD;
          2. 18-75 Years Old, female;&#xD;
&#xD;
          3. Expected survival &gt; 12 weeks;&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) score 0-2;&#xD;
&#xD;
          5. Patients who have previously been treated with second- line or above standard&#xD;
             treatment are failed (progress in treatment or recurrence within 6 months after&#xD;
             discontinuation of treatment);&#xD;
&#xD;
          6. According to the Immune-Modified Response Evaluation Criteria In Solid Tumors&#xD;
             (imRECIST) , there should be at least one measurable tumor foci；&#xD;
&#xD;
          7. Positive expression of Mesothelin in tumor tissue；&#xD;
&#xD;
          8. Creatinine ≤ 1.5×ULN or creatinine clearance ≥ 60ml / min;&#xD;
&#xD;
          9. alanine aminotransferase and aspartate aminotransferase ≤ 2.5×ULN , such as with liver&#xD;
             metastasis, ≤ 5×ULN;&#xD;
&#xD;
         10. Total bilirubin ≤ 2×ULN;&#xD;
&#xD;
         11. Hemoglobin≥90g/L(No blood transfusion within 14 days);&#xD;
&#xD;
         12. Absolute value of neutrophils ≥1.5×10^9/L;&#xD;
&#xD;
         13. Absolute counting of lymphocytes &gt;0.7×10^9/L;&#xD;
&#xD;
         14. Counting of Platelet≥80×10^9/L；&#xD;
&#xD;
         15. The venous access required for collection can be established without contraindications&#xD;
             for leukocyte collection;&#xD;
&#xD;
         16. Able to understand and sign the Informed Consent Document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Accompanied by other uncontrolled malignant tumors;&#xD;
&#xD;
          2. Active hepatitis B, hepatitis C, syphilis, HIV infection;&#xD;
&#xD;
          3. Insufficient function of important organs (heart, lung);&#xD;
&#xD;
          4. Any other uncontrolled active disease that impedes participation in the trial;&#xD;
&#xD;
          5. Any affairs could affect the safety of the subjects or purpose this trial;&#xD;
&#xD;
          6. Pregnant or lactating women, or patients who plan to be pregnancy during or after&#xD;
             treatment;&#xD;
&#xD;
          7. There are active or uncontrollable infections (except simple urinary tract infections&#xD;
             or upper respiratory tract infections) that require systemic therapy within 14 days or&#xD;
             14 days prior to enrollment；&#xD;
&#xD;
          8. The investigator believes that it is not appropriate to participate in the trial;&#xD;
&#xD;
          9. Received CAR-T treatment or other gene therapies before enrollment; Subjects suffering&#xD;
             disease affect the understanding of informed consent or unable to comply with study;&#xD;
             Unwilling or unable to comply with study requirements.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hui Zhao, doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai 6th People's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hui Zhao, doctor</last_name>
    <phone>021-64369181</phone>
    <email>ivy25502@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yincheng Teng, doctor</last_name>
    <phone>021-64369181</phone>
    <email>teng_yc@126.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai 6th People's Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hui Zhao</last_name>
      <phone>021-64369181</phone>
      <email>ivy25502@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>August 9, 2021</last_update_submitted>
  <last_update_submitted_qc>August 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai 6th People's Hospital</investigator_affiliation>
    <investigator_full_name>Zhao Hui</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <keyword>MESO</keyword>
  <keyword>CAR-T</keyword>
  <keyword>Ovarian cancer</keyword>
  <keyword>Refractory-Relapsed</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
  </intervention_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/NCT03814447
org study id: MESO-CART
nct id: NCT03814447
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The goal of this clinical trial is to study the safety and feasibility of anti- Mesothelin
      Chimeric Antigen Receptor T-Cell (MESO CAR-T cells) therapy for Refractory-Relapsed Ovarian
      Cancer
Primary Objectives:

      1. To determine the safety and feasibility of anti- MESO CAR-T cells therapy for
      Refractory-Relapsed Ovarian Cancer

      Secondary Objectives:

        1. To access the efficacy of anti- MESO CAR-T cells in patients with ovarian cancer.

        2. To determine in vivo dynamics and persistency of anti- MESO CAR-T cells

        3. To assess the quality of life in patients with ovarian cancer after treatment with anti-
           MESO CAR-T cells.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events (AEs) and Serious adverse event (SAEs)
time frame: 1 year post infusion
description: Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.03
measure: Cmax
time frame: 30 days post infusion
description: the highest concentration (Cmax) of anti-human MESO T cells in the peripheral blood after administration
measure: Tmax
time frame: 30 days post infusion
description: the time to reach the highest concentration (Tmax) of anti-human MESO T cells in the peripheral blood after administration
measure: AUC(0-30d)
time frame: 30 days post infusion
description: the area under the curve of 30 days of anti-human MESO T cells in the peripheral blood after administration
measure: Duration of Mesothelin-positive T cells in circulation
time frame: 90 days post infusion
description: Duration of Mesothelin-positive T cells in circulation
measure: ORR
time frame: 3 months post infusion
description: Overall response rate after administration
measure: PFS
time frame: 1 year post infusion
description: Progress Free Survival after administration
measure: EORTC Quality-of-Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL) of patients after administration
time frame: 1 year post infusion
description: This QLQ-C15-PAL score consists of 15 questions; two multi-item functional scales (physical and emotional functioning), two multi-item symptom scales (fatigue and pain) together with five single-item symptom scales (nausea/vomiting, dyspnea, insomnia, appetite loss, constipation) and one final question referring to overall QOL. The physical functioning scale is based on three questions regarding walking, activities of daily living and time spent in bed or in a chair. The emotional functioning scale is based on two questions that ask about feeling tense or depressed. Patients rated each question on a Likert scale from 1 (not at all) to 4 (very much), with the exception of overall QOL, which was rated from 1 (very poor) to 7 (excellent)
arm group label: anti- MESO CAR-T cells
arm group type: Experimental
description: The subjects in this arm will receive Cyclophosphamide 300mg/m2/d and Fludarabine 30mg/m2/d d-4~-2. Then anti- MESO CAR-T cells will be injected by a dose of 5×106/kg once at d1(rang from d1-3).
intervention type: Drug
intervention name: anti- MESO CAR-T cells
description: Autologous genetically modified anti- MESO CAR transduced T cells
arm group label: anti- MESO CAR-T cells
intervention type: Drug
intervention name: Fludarabine
description: Dose: 30mg/m2/d
arm group label: anti- MESO CAR-T cells
other name: FA
intervention type: Drug
intervention name: Cyclophosphamide
description: Dose: 300mg/m2/d
arm group label: anti- MESO CAR-T cells
other name: CTX
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hui Zhao, doctor
role: Principal Investigator
affiliation: Shanghai 6th People's Hospital
last name: Hui Zhao, doctor
phone: 021-64369181
email: ivy25502@hotmail.com
last name: Yincheng Teng, doctor
phone: 021-64369181
email: teng_yc@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai 6th People's Hospital
investigator full name: Zhao Hui
investigator title: professor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Cyclophosphamide
mesh term: Fludarabine
sharing ipd: No