xml: <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/NCT06018363</url>
    </required_header>
    <id_info>
      <org_study_id>QH10401-GC-01（0）</org_study_id>
      <nct_id>NCT06018363</nct_id>
    </id_info>
    <brief_title>Clinical Study on the Treatment of Malignant Brain Glioma by QH104 Cell Injection</brief_title>
    <official_title>Allogenic B7H3-targeting CAR-γδT Cell Therapy in r/r GBM</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Dushu Lake Hospital Affiliated to Soochow University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Dushu Lake Hospital Affiliated to Soochow University</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a study on the clinical application of chimeric antigen receptor modified γδ T cells&#xD;
        (CAR-γδ T cells) in relapsed and refractory B7H3 Positive malignant brain glioma.The main&#xD;
        purpose of this study was to evaluate the safety and feasibility of CAR-γδ T cell infusion in&#xD;
        patients with relapsed and refractory B7H3 Positive malignant brain glioma.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        γδT cells are known as &quot;a great candidate for car-t cells&quot;. Although they only account for 2%&#xD;
        - 5% of all T cells in our body, they are a natural killer.&#xD;
  &#xD;
        Treatment on this study includes six B7H3 CAR-γδ Tcell infusions over an 12 week period. B7H3&#xD;
        CAR-γδ T cells will be locoregionally administered via a CNS reservoir catheter without&#xD;
        lymphodepleting chemotherapy. The study will evaluate the safety, feasibility and maximum&#xD;
        tolerated dose (MTD) of B7H3 CAR-γδ T cell using a 3+3 study design and an 4 week evaluation&#xD;
        period. The total study duration will be 2 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</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>Phase 1: Incidence of Adverse Events (AEs)</measure>
      <time_frame>12 months</time_frame>
      <description>AE is defined as any adverse medical event from the date of the cell infusion to 12 months after B7H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1:Incidence of Dose-Limiting Toxicities (DLTs)</measure>
      <time_frame>First infusion date of B7H3 CAR-γδT cells up to 28 days</time_frame>
      <description>DLT was defined as B7H3 CAR-γδT cells-related events with onset within first 28 days following infusion:&#xD;
  The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting &gt; 2 weeks; Any B7H3 CAR-γδT cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1:Maximum tolerated dose (MTD)</measure>
      <time_frame>First infusion date of B7H3 CAR-γδT cells up to 28 days</time_frame>
      <description>MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1: Recommended phase 2 dose (RP2D)</measure>
      <time_frame>First infusion date of B7H3 CAR-γδT cells up to 28 days</time_frame>
      <description>The recommended dose for phase 2 was determined through phase 1 study.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 2: Best objective Response Rate</measure>
      <time_frame>12 months</time_frame>
      <description>The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the RANO assessment criterion.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Overall Survival (OS)</measure>
      <time_frame>12 months</time_frame>
      <description>OS is defined as the time from B7H3 CAR-γδT cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Progression Free Survival (PFS)</measure>
      <time_frame>12 months</time_frame>
      <description>PFS is defined as the time from the B7H3 CAR-γδT cells infusion date to the date of disease progression assessed by investigators and based on the RANO assessment criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics: Number and copy number of B7H3 CAR-γδT cells (phase 1 and phase 2)</measure>
      <time_frame>First infusion date of B7H3 CAR-γδT cells up to 28 days</time_frame>
      <description>Number and copy number of B7H3 CAR-γδT cells were assessed by number in cerebrospinal fluid(CSF). CSF samples were collected before and after cell infusion to detect the number and copy number of B7H3 CAR-γδT cells, and to evaluate the pharmacokinetics of B7H3 CAR-γδT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacodynamics: Peak level of cytokines in CSF (phase 1 and phase 2)</measure>
      <time_frame>First infusion date of B7H3 CAR-γδT cells up to 28 days</time_frame>
      <description>The cytokines mainly include interleukin-1 (IL-1 ), IL-6, IL-8, IL-10, interferon-γ (IFN-γ). Peak was defined as the maximum post-baseline level of the cytokine.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Brain Gliomas</condition>
    <arm_group>
      <arm_group_label>ARM</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with refractory or relapsed B7H3 positive GBM</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Allogenic B7H3 CAR-γδT cell</intervention_name>
      <description>Phase 1 dose escalation (3+3) : dose 1 (1 × 10^7 cells) , dose 2 (3 × 10^7 cells), dose 3 (1× 10^8 cells); Phase 2 : dose of RP2D.</description>
      <arm_group_label>ARM</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1)Age 18-70 years old (both ends included), both male and female;&#xD;
  &#xD;
            -  2)At least one evaluable lesion with previous biopsy or pathohistologic confirmation&#xD;
               of high-grade glioma (WHO grade IV), with imaging suggestive of continued progression&#xD;
               or recurrence after comprehensive treatment;&#xD;
  &#xD;
            -  3) Surgically resected pathological tissue capable of being used for&#xD;
               immunohistochemical detection of target proteins and positive for B7H3 expression;&#xD;
  &#xD;
            -  4) KPS ≥ 60 points;&#xD;
  &#xD;
            -  5)Expected survival &gt; 3 months;&#xD;
  &#xD;
            -  6)Substantially normal bone marrow reserve function and normal liver and renal&#xD;
               function (laboratory tests need to be fulfilled before receiving QH104 Cell Injection&#xD;
               for the first time):White blood cell count (WBC) ≥ 3 x 109/L;Lymphocyte count (LY) ≥&#xD;
               0.8 x 109/L;Hemoglobin (Hb) ≥ 90g/L;Platelet (PLT) ≥80×109/L;Albumin transaminase&#xD;
               (ALT) &amp; albumin transaminase (AST) &lt;1.5×ULN;Serum creatinine (Cr) &lt;1.5 x ULN;Total&#xD;
               bilirubin &lt; 1.5 x ULN;PT &amp; PTT ≤ 1.25 x ULN.&#xD;
  &#xD;
            -  7)No obvious hereditary diseases;&#xD;
  &#xD;
            -  8)Normal cardiac function with cardiac ejection index &gt;55%;&#xD;
  &#xD;
            -  9)No bleeding and coagulation disorders;&#xD;
  &#xD;
            -  10)Women of childbearing age (15-49 years old) must have had a pregnancy test with a&#xD;
               negative result within 7 days prior to the start of treatment, and subjects are&#xD;
               willing to use contraception during the clinical trial and for 3 months after the last&#xD;
               cell infusion;&#xD;
  &#xD;
            -  11) Sign the informed consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1)Pregnant and lactating women;&#xD;
  &#xD;
            -  2)Those with organ failure:Heart: Class III and IV;Liver: up to grade C of the&#xD;
               Child-Turcotte Liver -Function Classification;Kidney: chronic kidney disease stage 4&#xD;
               or above; renal insufficiency stage III or above;Lungs: symptoms of severe respiratory&#xD;
               failure with involvement of other organs;Brain: central nervous system abnormalities&#xD;
               or impaired consciousness;&#xD;
  &#xD;
            -  3)patients with combined second tumors;&#xD;
  &#xD;
            -  4)patients with active hepatitis B or C virus, HIV infection, or other untreated&#xD;
               active infection;&#xD;
  &#xD;
            -  5)any severe, uncontrolled systemic autoimmune disease or any unstable systemic&#xD;
               disease, including but not limited to systemic lupus erythematosus, rheumatoid&#xD;
               arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis;&#xD;
  &#xD;
            -  6)Current systemic use of steroid cell (except for recent or current use of inhaled&#xD;
               steroids) substances;&#xD;
  &#xD;
            -  7) have a chronic disease requiring immunologic or hormonal therapy;&#xD;
  &#xD;
            -  8) have an allergy to immunotherapy and related cells;&#xD;
  &#xD;
            -  9) 10)Patients with a history of organ transplantation or who are awaiting organ&#xD;
               transplantation;&#xD;
  &#xD;
            -  10)Participation in other clinical trials within the previous 30 days;&#xD;
  &#xD;
            -  11)Those who are not suitable for clinical trials for other reasons in the opinion of&#xD;
               the investigator.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Dushu Lake Hospital Affiliated to Soochow University</name>
        <address>
          <city>Suzhou</city>
          <state>Jiangsu</state>
          <zip>215125</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yulun Huang</last_name>
        <phone>+86 130 1388 9432</phone>
        <email>huangyulun@suda.edu.cn</email>
      </contact>
      <contact_backup>
        <last_name>Xuetao Li</last_name>
        <phone>+86 151 9563 7789</phone>
        <email>lixuetao0405@126.com</email>
      </contact_backup>
      <investigator>
        <last_name>Yulun Huang</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Xuetao Li</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>B7H3</keyword>
    <keyword>CAR-γδT</keyword>
    <keyword>GBM</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Glioma</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06018363
  org study id: QH10401-GC-01（0）
  nct id: NCT06018363
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a study on the clinical application of chimeric antigen receptor modified γδ T cells
        (CAR-γδ T cells) in relapsed and refractory B7H3 Positive malignant brain glioma.The main
        purpose of this study was to evaluate the safety and feasibility of CAR-γδ T cell infusion in
        patients with relapsed and refractory B7H3 Positive malignant brain glioma.
  γδT cells are known as "a great candidate for car-t cells". Although they only account for 2%
        - 5% of all T cells in our body, they are a natural killer.
  
        Treatment on this study includes six B7H3 CAR-γδ Tcell infusions over an 12 week period. B7H3
        CAR-γδ T cells will be locoregionally administered via a CNS reservoir catheter without
        lymphodepleting chemotherapy. The study will evaluate the safety, feasibility and maximum
        tolerated dose (MTD) of B7H3 CAR-γδ T cell using a 3+3 study design and an 4 week evaluation
        period. The total study duration will be 2 years.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Phase 1: Incidence of Adverse Events (AEs)
  time frame: 12 months
  description: AE is defined as any adverse medical event from the date of the cell infusion to 12 months after B7H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
  measure: Phase 1:Incidence of Dose-Limiting Toxicities (DLTs)
  time frame: First infusion date of B7H3 CAR-γδT cells up to 28 days
  description: DLT was defined as B7H3 CAR-γδT cells-related events with onset within first 28 days following infusion:
  The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting > 2 weeks; Any B7H3 CAR-γδT cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.
  measure: Phase 1:Maximum tolerated dose (MTD)
  time frame: First infusion date of B7H3 CAR-γδT cells up to 28 days
  description: MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
  measure: Phase 1: Recommended phase 2 dose (RP2D)
  time frame: First infusion date of B7H3 CAR-γδT cells up to 28 days
  description: The recommended dose for phase 2 was determined through phase 1 study.
  measure: Phase 2: Best objective Response Rate
  time frame: 12 months
  description: The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the RANO assessment criterion.
  measure: Phase 2: Overall Survival (OS)
  time frame: 12 months
  description: OS is defined as the time from B7H3 CAR-γδT cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
  measure: Phase 2: Progression Free Survival (PFS)
  time frame: 12 months
  description: PFS is defined as the time from the B7H3 CAR-γδT cells infusion date to the date of disease progression assessed by investigators and based on the RANO assessment criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
  measure: Pharmacokinetics: Number and copy number of B7H3 CAR-γδT cells (phase 1 and phase 2)
  time frame: First infusion date of B7H3 CAR-γδT cells up to 28 days
  description: Number and copy number of B7H3 CAR-γδT cells were assessed by number in cerebrospinal fluid(CSF). CSF samples were collected before and after cell infusion to detect the number and copy number of B7H3 CAR-γδT cells, and to evaluate the pharmacokinetics of B7H3 CAR-γδT.
  measure: Pharmacodynamics: Peak level of cytokines in CSF (phase 1 and phase 2)
  time frame: First infusion date of B7H3 CAR-γδT cells up to 28 days
  description: The cytokines mainly include interleukin-1 (IL-1 ), IL-6, IL-8, IL-10, interferon-γ (IFN-γ). Peak was defined as the maximum post-baseline level of the cytokine.
  arm group label: ARM
  arm group type: Experimental
  description: Patients with refractory or relapsed B7H3 positive GBM
  intervention type: Biological
  intervention name: Allogenic B7H3 CAR-γδT cell
  description: Phase 1 dose escalation (3+3) : dose 1 (1 × 10^7 cells) , dose 2 (3 × 10^7 cells), dose 3 (1× 10^8 cells); Phase 2 : dose of RP2D.
  arm group label: ARM
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Glioma