<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/NCT04480788</url>
  </required_header>
  <id_info>
    <org_study_id>PG-CART-07-001</org_study_id>
    <nct_id>NCT04480788</nct_id>
  </id_info>
  <brief_title>CD7-CART in the Treatment of r / r CD7 Positive Hemolymph System Malignancies on Increasing Dose and Open Label Study</brief_title>
  <official_title>Early Clinical Study on Increasing Dose and Open Label of T Cell Injection Targeting CD7 Autologous Chimeric Antigen Receptor in the Treatment of Relapsed / Refractory CD7 Positive Hemolymph System Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PersonGen BioTherapeutics (Suzhou) Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First Affiliated Hospital of Zhengzhou University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>PersonGen BioTherapeutics (Suzhou) Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase I was a single arm, open label, dose increasing study to explore the safety, tolerance&#xD;
      and Cytodynamic characteristics of the drug, and to preliminarily observe the efficacy of the&#xD;
      study drug in relapsed / refractory CD7 Positive hematolymph system malignant tumor patients,&#xD;
      so as to explore the clinical applicable dose of phase II. Since the activity and toxicity of&#xD;
      cellular drugs (long-term survival drugs) do not have obvious dose dependence, and the&#xD;
      increase of their dose may be accompanied by the increase of toxicity, rather than necessary&#xD;
      for therapeutic effect, it is not necessarily suitable to recommend the effective dose&#xD;
      according to the maximum tolerable dose (MTD). Therefore, this study will be based on the&#xD;
      safety data, as well as the preliminary efficacy, efficacy and drug The end point of&#xD;
      pharmacokinetics (ORR, the content of CD7 Positive Cells, the expansion and duration of car-t&#xD;
      cells) were comprehensively considered to determine the recommended dose for phase II&#xD;
      clinical trial.Main research purposes Objective to evaluate the safety and tolerability of T&#xD;
      cell injection targeting CD7 autologous chimeric antigen receptor in the treatment of&#xD;
      relapsed / refractory CD7 Positive hematological and lymphoid malignancies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 24, 2020</start_date>
  <completion_date type="Anticipated">August 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2022</primary_completion_date>
  <phase>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>
    <intervention_model_description>CD7-CART</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose-limiting toxicity (DLT)</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety results</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Number of adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The maximum concentration (Cmax）</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>the time to reach the maximum concentration (Tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The area under the curve (auc0-28d ) at 28d respectively after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Absolute value of CD7 Positive Cells in peripheral blood at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The proportion of CD7 Positive Cells in peripheral blood at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The total response rate was 3 months and 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival (OS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Time from initiation of CD7 car-t cell therapy to death (for any reason)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Search Results Featured snippet from the web Duration of response (DOR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The time from the first assessment of Cr or PR to the first assessment of recurrence or progression of the disease or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The time from the beginning of treatment with CD7 car-t cells to the first progression of disease or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The positive rate of human anti car antibody at each time point</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">9</enrollment>
  <condition>T Lymphoblastic Leukemia/Lymphoma</condition>
  <condition>Extramedullary NK-T-cell Lymphoma, Nasal Type</condition>
  <condition>Peripheral T-cell Lymphoma, Nonspecific</condition>
  <condition>Angioimmunoblastic T-cell Lymphoma</condition>
  <condition>Enteropathy-Associated T-Cell Lymphoma</condition>
  <condition>Anaplastic Large Cell Lymphoma, ALK-negative</condition>
  <condition>T-cell Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>T cell injection targeting CD7 chimeric antigen receptor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>T cell injection targeting CD7 chimeric antigen receptor</intervention_name>
    <description>Drug name: T cell injection targeting CD7 autologous chimeric antigen receptor. Package specification: 10-50ml bag, 1-4 bags / person, which is determined according to the body weight of the subject and the effective content of cell preparation</description>
    <arm_group_label>T cell injection targeting CD7 chimeric antigen receptor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The age ranged from 7 to 70 years (including the cut-off value), regardless of gender&#xD;
&#xD;
          -  The expected survival time was more than 6 weeks&#xD;
&#xD;
          -  ECOG score 0-1&#xD;
&#xD;
          -  Malignant lymphoma (including but not limited to acute T-lymphoblastic leukemia /&#xD;
             lymphoma; extramedullary NK / T-cell lymphoma, nasal type; peripheral T-cell lymphoma,&#xD;
             nonspecific; vascular immunoblastic T-cell lymphoma; intestinal disease associated&#xD;
             T-cell lymphomas; anaplastic large cell lymphoma (ALK -); T-cell lymphoblastic&#xD;
             leukemia)&#xD;
&#xD;
          -  When screening, hematological malignancies with CD7 Positive confirmed by bone marrow&#xD;
             examination or tumor pathology with positive rate of CD7 ≥ 30%, meeting one of the&#xD;
             following conditions:&#xD;
&#xD;
               1. At least two chemotherapy regimens failed or did not achieve complete remission&#xD;
                  or relapse;&#xD;
&#xD;
               2. Patients who relapsed after stem cell transplantation were not affected by other&#xD;
                  treatment methods;&#xD;
&#xD;
          -  For peripheral blood involved acute T-lymphoblastic leukemia / lymphoma and NK /&#xD;
             T-cell lymphoma, patients with TCR rearrangement were detected by ngs&#xD;
&#xD;
          -  The liver and kidney function, heart and lung function meet the following&#xD;
             requirements:&#xD;
&#xD;
               1. Creatinine ≤ 1.5 ULN;&#xD;
&#xD;
               2. LVEF ≥ 45%;&#xD;
&#xD;
               3. Blood oxygen saturation &gt; 91%;&#xD;
&#xD;
               4. The total bilirubin ≤ 2 × ULN; ALT and AST ≤ 2.5 × ULN; the abnormal ALT and AST&#xD;
                  caused by diseases (such as liver infiltration or bile duct obstruction) can be&#xD;
                  relaxed to ≤ 5 × ULN;&#xD;
&#xD;
          -  Understand the experiment and have signed the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Those who need immunosuppressant;&#xD;
&#xD;
          -  For intestinal disease-related T-cell lymphoma, patients with intestinal ulcer or&#xD;
             hematochezia were examined by colonoscopy;&#xD;
&#xD;
          -  In addition to cervical carcinoma in situ, basal cell or squamous cell skin cancer,&#xD;
             local prostate cancer after radical operation, and breast ductal carcinoma in situ&#xD;
             after radical operation;&#xD;
&#xD;
          -  The patients with positive HBsAg or HBcAb and HBV DNA titer in peripheral blood were&#xD;
             not within the normal reference value; those with positive anti HCV antibody and&#xD;
             positive HCV RNA in peripheral blood; those with HIV antibody positive and&#xD;
             cytomegalovirus DNA positive Syphilis was positive;&#xD;
&#xD;
          -  Severe heart disease: including but not limited to unstable angina pectoris,&#xD;
             myocardial infarction (within 6 months before screening), congestive heart failure&#xD;
             (NYHA classification ≥ III), severe arrhythmia;&#xD;
&#xD;
          -  Unstable systemic diseases judged by researchers: including but not limited to severe&#xD;
             liver, kidney or metabolic diseases requiring drug treatment;&#xD;
&#xD;
          -  Within 7 days before screening, there were active or uncontrollable infections&#xD;
             requiring systemic treatment (except for mild genitourinary system infection and upper&#xD;
             respiratory tract infection);&#xD;
&#xD;
          -  Pregnant or lactating women, female subjects planning pregnancy within 1 year after&#xD;
             cell reinfusion or male subjects whose partners plan to conceive within 1 year after&#xD;
             cell reinfusion;&#xD;
&#xD;
          -  Patients who had received car-t therapy or other gene modified cell therapy before&#xD;
             screening;&#xD;
&#xD;
          -  Subjects who were receiving systemic steroid therapy or were receiving systemic&#xD;
             steroid therapy for 7 days were excluded;&#xD;
&#xD;
          -  Participated in other clinical studies within 3 months before screening;&#xD;
&#xD;
          -  There was evidence of central nervous system invasion during screening;&#xD;
&#xD;
          -  According to the judgment of the researchers, it does not conform to the condition of&#xD;
             cell preparation;&#xD;
&#xD;
          -  Other researchers think it is not suitable to be included in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Mingzhi Zhang, Doctor</last_name>
    <phone>+8613838565629</phone>
    <email>mingzhi_zhang@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>First Affiliated Hospital of Zhengzhou University</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mingzhi Zhang, doctor</last_name>
      <phone>+8613838565629</phone>
      <email>mingzhi_zhang@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>January 4, 2021</last_update_submitted>
  <last_update_submitted_qc>January 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
    <mesh_term>Lymphoma, Large-Cell, Anaplastic</mesh_term>
    <mesh_term>Enteropathy-Associated T-Cell Lymphoma</mesh_term>
    <mesh_term>Immunoblastic Lymphadenopathy</mesh_term>
  </condition_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/NCT04480788
org study id: PG-CART-07-001
nct id: NCT04480788
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Phase I was a single arm, open label, dose increasing study to explore the safety, tolerance
      and Cytodynamic characteristics of the drug, and to preliminarily observe the efficacy of the
      study drug in relapsed / refractory CD7 Positive hematolymph system malignant tumor patients,
      so as to explore the clinical applicable dose of phase II. Since the activity and toxicity of
      cellular drugs (long-term survival drugs) do not have obvious dose dependence, and the
      increase of their dose may be accompanied by the increase of toxicity, rather than necessary
      for therapeutic effect, it is not necessarily suitable to recommend the effective dose
      according to the maximum tolerable dose (MTD). Therefore, this study will be based on the
      safety data, as well as the preliminary efficacy, efficacy and drug The end point of
      pharmacokinetics (ORR, the content of CD7 Positive Cells, the expansion and duration of car-t
      cells) were comprehensively considered to determine the recommended dose for phase II
      clinical trial.Main research purposes Objective to evaluate the safety and tolerability of T
      cell injection targeting CD7 autologous chimeric antigen receptor in the treatment of
      relapsed / refractory CD7 Positive hematological and lymphoid malignancies.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: CD7-CART
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicity (DLT)
time frame: Up to 2 years
measure: Safety results
time frame: Up to 2 years
description: Number of adverse events
measure: PK
time frame: Up to 2 years
description: The maximum concentration (Cmax）
measure: PK
time frame: Up to 2 years
description: the time to reach the maximum concentration (Tmax)
measure: PK
time frame: Up to 2 years
description: The area under the curve (auc0-28d ) at 28d respectively after administration
measure: PD
time frame: Up to 2 years
description: Absolute value of CD7 Positive Cells in peripheral blood at each time point
measure: PD
time frame: Up to 2 years
description: The proportion of CD7 Positive Cells in peripheral blood at each time point
measure: ORR
time frame: Up to 2 years
description: The total response rate was 3 months and 6 months
measure: overall survival (OS)
time frame: Up to 2 years
description: Time from initiation of CD7 car-t cell therapy to death (for any reason)
measure: Search Results Featured snippet from the web Duration of response (DOR)
time frame: Up to 2 years
description: The time from the first assessment of Cr or PR to the first assessment of recurrence or progression of the disease or death from any cause
measure: Progression-free survival (PFS)
time frame: Up to 2 years
description: The time from the beginning of treatment with CD7 car-t cells to the first progression of disease or death from any cause
measure: Immunogenicity
time frame: Up to 2 years
description: The positive rate of human anti car antibody at each time point
arm group label: T cell injection targeting CD7 chimeric antigen receptor
arm group type: Experimental
intervention type: Biological
intervention name: T cell injection targeting CD7 chimeric antigen receptor
description: Drug name: T cell injection targeting CD7 autologous chimeric antigen receptor. Package specification: 10-50ml bag, 1-4 bags / person, which is determined according to the body weight of the subject and the effective content of cell preparation
arm group label: T cell injection targeting CD7 chimeric antigen receptor
criteria: 
gender: All
minimum age: 7 Years
maximum age: 70 Years
healthy volunteers: No
last name: Mingzhi Zhang, Doctor
phone: +8613838565629
email: mingzhi_zhang@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Lymphoma, Large-Cell, Anaplastic
mesh term: Enteropathy-Associated T-Cell Lymphoma
mesh term: Immunoblastic Lymphadenopathy