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/NCT06013111</url>
    </required_header>
    <id_info>
      <org_study_id>CEA-CN-A3</org_study_id>
      <nct_id>NCT06013111</nct_id>
    </id_info>
    <brief_title>An Exploratory Clinical Study Evaluating the Safety and Efficacy of Anti-CEA-CAR-T Cells Injection in Patients With CEA+ Locally Advanced and/or Metastatic Solid Tumors</brief_title>
    <official_title>An Exploratory Clinical Study Evaluating the Safety and Efficacy of Anti-CEA-CAR-T Cells Injection in Patients With CEA+ Locally Advanced and/or Metastatic Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>China Medical University, China</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Shanghai First Song Therapeutics Co., Ltd</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>China Medical University, China</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>
        This is a single-center, open-label clinical study of anti-CEA-CAR-T cells for CEA+ patients&#xD;
        with locally advanced and/or metastatic solid tumors. In this study, a single-dose regimen&#xD;
        was designed, and the investigator had the discretion to decide whether the patient received&#xD;
        more than once CAR T-cell therapy.This study intends to include CEA+ patients with locally&#xD;
        advanced and/or metastatic solid tumors.They will take the anti-CEA-CAR-T cell transfusion&#xD;
        after a screening period, mononuclear cell (PBMC) collection, bridging therapy if necessary,&#xD;
        and lymphocyte clearance pretreatment period.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2026</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Dose-limiting toxicity</measure>
      <time_frame>21 days within anti-CEA-CAR-T cell infusion</time_frame>
      <description>Dose-limiting toxicity</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective response rate</measure>
      <time_frame>4week,8week,3month,6month,9month and12month after the anti-CEA-CAR-T cell infusion</time_frame>
      <description>Objective response rate</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">9</enrollment>
    <condition>Carcinoma</condition>
    <arm_group>
      <arm_group_label>Anti-CEA-CAR-T cell infusion</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Anti-CEA-CAR-T cell is administered as a single intravenous infusion. Follow-up infusions are based on the investigator's decision.The dose group to be infusion was 0.3×10^7 CAR-T cells/kg, 1×10^7 CAR-T cells/kg, and 3×10^7 CAR-T cells/kg based on the 3+3 dose escalation principle. The infusion dose refers to the number of CAR-positive cells.The patients will receive lymphocyte clearance therapy with cyclophosphamide and fludarabine before the infusion.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Intravenous infusion anti-CEA-CAR-T cell</intervention_name>
      <description>Anti-CEA-CAR-T cell is administered as a single intravenous infusion. Follow-up infusions are based on the investigator's decision.The dose group to be infusion was 0.3×10^7 CAR-T cells/kg, 1×10^7 CAR-T cells/kg, and 3×10^7 CAR-T cells/kg based on the 3+3 dose escalation principle. The infusion dose refers to the number of CAR-positive cells.</description>
      <arm_group_label>Anti-CEA-CAR-T cell infusion</arm_group_label>
      <other_name>cyclophosphamide</other_name>
      <other_name>fludarabine</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients should understand and sign informed consent forms and voluntarily participate&#xD;
               in clinical studies;&#xD;
  &#xD;
            2. Age≥ 18, &lt; 70 years old, gender is not limited;&#xD;
  &#xD;
            3. Locally advanced and/or metastatic solid tumors; Cytoplasmic and/or membranous high&#xD;
               CEA expression in tumor tissue is required (expression intensity of 2+ and above on&#xD;
               the area ≥50%) ;&#xD;
  &#xD;
            4. Histology-confirmed solid tumors (gastric cancer, colorectal cancer, esophageal&#xD;
               cancer, small bowel cancer, pancreas adenocarcinoma and other digestive system tumors&#xD;
               are predominant), conventional treatment is ineffective or Intolerability conventional&#xD;
               treatment or lack of effective treatment;&#xD;
  &#xD;
            5. According to RECIST v 1.1, at least one measurable lesion with a maximum lesion&#xD;
               diameter not exceeding 6 cm;&#xD;
  &#xD;
            6. Expected survival≥ 12 weeks;&#xD;
  &#xD;
            7. ECOG score≤ 2 ;&#xD;
  &#xD;
            8. Adequate hematological function ; have no performed blood transfusion or received cell&#xD;
               growth factor within 7 days before screening hematological evaluation:&#xD;
  &#xD;
                 -  Neutrophil ≥ 1.0×10^9/L&#xD;
  &#xD;
                 -  Hemoglobin≥ 80g/L&#xD;
  &#xD;
                 -  Platelet ≥ 75×10^9/L&#xD;
  &#xD;
                 -  Lymphocytes ≥ 0.5×10^9/L&#xD;
  &#xD;
            9. Adequate liver function: serum total bilirubin ≤1.5× ULN (excluding Gilbert's&#xD;
               syndrome); AST and ALT≤2.5×ULN；( AST and ALT ≤5×ULN with liver metastasis)&#xD;
  &#xD;
           10. Adequate renal function: creatinine ≤1.5× ULN or endogenous creatinine clearance ≥50&#xD;
               mL/min;&#xD;
  &#xD;
           11. LVEF ≥ 50%;&#xD;
  &#xD;
           12. There was no evidence that subjects had difficulty breathing at rest or pulse&#xD;
               oximetry&gt;90% when breathing indoor air;&#xD;
  &#xD;
           13. Sufficient intravenous access for apheresis; no other contraindications to blood cell&#xD;
               separation;&#xD;
  &#xD;
           14. The pregnancy test for women of childbearing age must be negative. All subjects must&#xD;
               agree to take effective contraception from the signing of the informed consent to 6&#xD;
               months after the last dose of the study drug infusion.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Previously using any CAR-T cell products or other genetically modified T cell&#xD;
               therapies;&#xD;
  &#xD;
            2. Patients who are waiting for organ transplantation or with a history of allogeneic&#xD;
               stem cell or solid organ transplantation;&#xD;
  &#xD;
            3. Patients with acute or uncontrolled active infection, including but not limited to&#xD;
               active tuberculosis;&#xD;
  &#xD;
            4. Patients with Hepatitis B infection (HBV surface antigen positive and/or hepatitis B&#xD;
               core antibody positive and hepatitis B DNA &gt;10^3 copies /mL) ; hepatitis C&#xD;
               infection(hepatitis C antibodies positive) ; Syphilis infection (antibody positive),&#xD;
               HIV infection (antibody positive);&#xD;
  &#xD;
            5. Patients with hyponatremia and/or hypokalemia, blood sodium &lt;125mmol/L and/or blood&#xD;
               potassium&lt;3.5mmol/L (Sodium and/or potassium supplementation may be given before&#xD;
               participating in the study to restore blood sodium and/or potassium above this level);&#xD;
  &#xD;
            6. Imaging results the proportion of liver replaced by tumor ≥50%;&#xD;
  &#xD;
            7. Patients who taken continuous systemic steroids within 14 days before apheresis or&#xD;
               within 72 hours before cell therapy (prednisone&gt; 5 mg/day or equivalent dose of other&#xD;
               hormones), excepting for those who use inhaled Steroid hormones;&#xD;
  &#xD;
            8. Systemic sexualization is accepted 2 weeks before apheresis or 5 half-lives (whichever&#xD;
               is shorter). Toxicity to previous antineoplastic therapy has not recovered (based on&#xD;
               CTCAE version 5.0 assessment); excepting for alopecia, pigmentation and other&#xD;
               tolerable events judged by the investigator or permitted laboratory abnormalities&#xD;
               according to the protocol;&#xD;
  &#xD;
            9. Antibody therapy within 4 weeks before apheresis and preconditioning;&#xD;
  &#xD;
           10. Anti-PD-1/PD-L1 monoclonal antibody therapy within 4 weeks before apheresis and&#xD;
               preconditioning;&#xD;
  &#xD;
           11. Immunostimulation or immunosuppressive therapy within 28 days prior to apheresis;&#xD;
  &#xD;
           12. Radiotherapy within 28 days prior to apheresis, except limited local palliative&#xD;
               radiotherapy;&#xD;
  &#xD;
           13. Patients with other malignant tumors within the past 5 years or at the present (except&#xD;
               for basal cell carcinoma of the skin, breast/cervix Carcinoma in situ and other&#xD;
               malignant tumors that have not been treated in the past five years have been&#xD;
               effectively controlled);&#xD;
  &#xD;
           14. Patients with active ulcers or active gastrointestinal bleeding that are difficult to&#xD;
               control;&#xD;
  &#xD;
           15. Patients with previous medical history of central nervous system (CNS) primary or&#xD;
               metastatic tumors including meningeal metastases, unless previously treated for brain&#xD;
               metastases, who are currently asymptomatic, and do not need steroid or enzyme-inducing&#xD;
               antiepileptic drug treatment within 14 days before screening;&#xD;
  &#xD;
           16. Patients with other central nervous system diseases that may affect the safety of the&#xD;
               subjects as judged by the researchers (such as epileptic seizures, cerebral&#xD;
               hemorrhage, dementia, etc.);&#xD;
  &#xD;
           17. Patients with uncontrolled hypertension, unstable angina, NYHA III or higher-grade&#xD;
               congestive heart failure with an ejection fraction of the heart below 50%, or an ECG&#xD;
               with significant abnormalities, serious arrhythmias requiring treatment and medical&#xD;
               history of myocardial infarction within 6 months prior to initiation of study&#xD;
               treatment;&#xD;
  &#xD;
           18. Patients with severe respiratory diseases before apheresis, such as interstitial lung&#xD;
               disease, active pulmonary tuberculosis;&#xD;
  &#xD;
           19. Patients with active or past autoimmune diseases that may relapse (such as systemic&#xD;
               lupus erythematosus, rheumatoid arthritis, etc.), except for the following diseases:&#xD;
               type 1 diabetes, hypothyroidism that only needs hormone replacement therapy, skin&#xD;
               diseases that do not require systemic therapy (such as vitiligo, psoriasis or hair&#xD;
               loss);&#xD;
  &#xD;
           20. Any serious or uncontrollable systemic disease, systemic Complications, other serious&#xD;
               concurrent diseases (such as hemophagocytic syndrome, etc.), special cases of tumor&#xD;
               conditions according to the investigator's judgment that may make patients unsuitable&#xD;
               for entry into the study or affect compliance with the protocol, or Significant&#xD;
               interference with the correct assessment of drug safety, toxicity, and effectiveness;&#xD;
  &#xD;
           21. Received any major surgery within 4 weeks before apheresis (except exploratory&#xD;
               laparotomy or laparoscopy exploration) or severe trauma; Any major surgery during the&#xD;
               DLT observation period, or has not yet completely recovered from any previous invasive&#xD;
               procedure;&#xD;
  &#xD;
           22. Patient allergic or intolerant to the preconditioning drugs that may be used in the&#xD;
               research process or the drugs for symptomatic treatment of CRS , including but not&#xD;
               limited to fludarabine and cyclophosphamide or tocilizumab;Known hypersensitivity to&#xD;
               the components of anti-CEA-CAR-T; or have any history of severe allergies, for&#xD;
               example, anaphylactic shock;&#xD;
  &#xD;
           23. Patients who have participated in other interventional clinical trials within 1 month&#xD;
               before administration;&#xD;
  &#xD;
           24. Pregnant or lactating women;&#xD;
  &#xD;
           25. Patients of childbearing age who are unwilling or unable to use reliable contraception&#xD;
               during the study period;&#xD;
  &#xD;
           26. Patients who are unable or unwilling to comply with clinical protocols as judged by&#xD;
               the investigator;&#xD;
  &#xD;
           27. Persons involved in the study plan and execution.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Zhenning Wang, doctor</last_name>
      <role>Principal Investigator</role>
      <affiliation>The First Affiliated Hospital of China Medical Univeristy</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Funan Liu, doctor</last_name>
      <role>Principal Investigator</role>
      <affiliation>The First Affiliated Hospital of China Medical Univeristy</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Shuhui Song, bachelor</last_name>
      <phone>024-83281137</phone>
      <email>593900927@qq.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>First Hospital of China Medical University</investigator_affiliation>
      <investigator_full_name>Funan Liu</investigator_full_name>
      <investigator_title>professor</investigator_title>
    </responsible_party>
    <keyword>CAR-T</keyword>
    <keyword>solid tumor</keyword>
    <keyword>Cell therapy</keyword>
    <keyword>CEA</keyword>
    <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>
  
  
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/NCT06013111
  org study id: CEA-CN-A3
  nct id: NCT06013111
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-center, open-label clinical study of anti-CEA-CAR-T cells for CEA+ patients
        with locally advanced and/or metastatic solid tumors. In this study, a single-dose regimen
        was designed, and the investigator had the discretion to decide whether the patient received
        more than once CAR T-cell therapy.This study intends to include CEA+ patients with locally
        advanced and/or metastatic solid tumors.They will take the anti-CEA-CAR-T cell transfusion
        after a screening period, mononuclear cell (PBMC) collection, bridging therapy if necessary,
        and lymphocyte clearance pretreatment period.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose-limiting toxicity
  time frame: 21 days within anti-CEA-CAR-T cell infusion
  description: Dose-limiting toxicity
  measure: Objective response rate
  time frame: 4week,8week,3month,6month,9month and12month after the anti-CEA-CAR-T cell infusion
  description: Objective response rate
  arm group label: Anti-CEA-CAR-T cell infusion
  arm group type: Experimental
  description: Anti-CEA-CAR-T cell is administered as a single intravenous infusion. Follow-up infusions are based on the investigator's decision.The dose group to be infusion was 0.3×10^7 CAR-T cells/kg, 1×10^7 CAR-T cells/kg, and 3×10^7 CAR-T cells/kg based on the 3+3 dose escalation principle. The infusion dose refers to the number of CAR-positive cells.The patients will receive lymphocyte clearance therapy with cyclophosphamide and fludarabine before the infusion.
  intervention type: Biological
  intervention name: Intravenous infusion anti-CEA-CAR-T cell
  description: Anti-CEA-CAR-T cell is administered as a single intravenous infusion. Follow-up infusions are based on the investigator's decision.The dose group to be infusion was 0.3×10^7 CAR-T cells/kg, 1×10^7 CAR-T cells/kg, and 3×10^7 CAR-T cells/kg based on the 3+3 dose escalation principle. The infusion dose refers to the number of CAR-positive cells.
  arm group label: Anti-CEA-CAR-T cell infusion
  other name: cyclophosphamide
  other name: fludarabine
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Zhenning Wang, doctor
  role: Principal Investigator
  affiliation: The First Affiliated Hospital of China Medical Univeristy
  last name: Funan Liu, doctor
  role: Principal Investigator
  affiliation: The First Affiliated Hospital of China Medical Univeristy
  last name: Shuhui Song, bachelor
  phone: 024-83281137
  email: 593900927@qq.com
  responsible party type: Principal Investigator
  investigator affiliation: First Hospital of China Medical University
  investigator full name: Funan Liu
  investigator title: professor
  mesh term: Cyclophosphamide
  mesh term: Fludarabine
  sharing ipd: No