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/NCT05990621</url>
    </required_header>
    <id_info>
      <org_study_id>Anti-CD70 CAR-T Cell Injection</org_study_id>
      <nct_id>NCT05990621</nct_id>
    </id_info>
    <brief_title>Anti-CD70 CAR-T Cell Injection in Patients With CD70-positive Advanced Urologic Neoplasms</brief_title>
    <official_title>A Single-arm, Open-label, Dose-escalation/Expansion, Early-phase Clinical Study of Anti-CD70 CAR-T Cell Injection in Patients With CD70-positive Advanced Urological Neoplasms</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Changhai Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>UTC Therapeutics Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Changhai Hospital</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-arm, open-label, exploratory clinical study to evaluate the safety,&#xD;
        tolerability and preliminary efficacy of Anti-CD70 CAR-T cell injection in patients with&#xD;
        CD70-positive Advanced Urologic Neoplasms.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study will include two parts, dose escalation phase (accelerated titration and 3+3&#xD;
        design) followed by a dose expansion phase. All eligible participants will receive a&#xD;
        conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by CAR-T cell&#xD;
        injection.&#xD;
  &#xD;
        The dose escalation phase will determine the maximum tolerated dose (MTD) of Anti-CD70 CAR-T&#xD;
        cell injection. Additional patients will be enrolled in the dose expansion phase to further&#xD;
        characterize the safety profile and evaluate the efficacy of Anti-CD70 CAR-T cell injection,&#xD;
        and establish recommended phase 2 dose (RP2D).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 31, 2023</start_date>
    <completion_date type="Anticipated">March 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">January 31, 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>
      <intervention_model_description>Accelerated titration and 3+3 design dose escalation phase followed by dose expansion phase</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Adverse Events (AEs)</measure>
      <time_frame>2 years</time_frame>
      <description>Incidence and severity of adverse events.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serious Adverse Events (SAEs)</measure>
      <time_frame>2 years</time_frame>
      <description>Incidence and severity of serious adverse events.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Adverse Events of Special Interest (AESI)</measure>
      <time_frame>2 years</time_frame>
      <description>Incidence and severity of adverse event of special interest.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Identification of Maximum Tolerated Dose (MTD)</measure>
      <time_frame>4 weeks after the CAR-T cells infusion</time_frame>
      <description>Incidence and severity of dose-limiting toxicities (DLTs) following infusion of UCL70802 cell injection, at each dose level tested in dose escalation phase.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>2 years</time_frame>
      <description>The Objective Response Rate (ORR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Overall Response (DOR)</measure>
      <time_frame>2 years</time_frame>
      <description>Time from documentation of disease response to disease progression.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival (PFS)</measure>
      <time_frame>2 years</time_frame>
      <description>PFS is defined as the time from CAR-T infusion to the date of the disease progression or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>2 years</time_frame>
      <description>OS is defined as the time from CAR-T infusion to the date of death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Bio-distribution of Anti-CD70 CAR-T cells</measure>
      <time_frame>2 years</time_frame>
      <description>CAR copies will be measured by qPCR to evaluate the expansion and persistence of CAR-T cells in vivo.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cytokine Level in Peripheral Blood</measure>
      <time_frame>2 years</time_frame>
      <description>Level of cytokines (IFN-γ, IL-6, IL-2, etc.) in serum.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with anti-drug antibodies.</measure>
      <time_frame>2 years</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>CD70-positive Advanced Urologic Neoplasms</condition>
    <arm_group>
      <arm_group_label>Anti-CD70 CAR-T cells</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Anti-CD70 CAR-T cells are autologous genetically modified T cells.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Anti-CD70 CAR-T cells</intervention_name>
      <description>0.6×106/Kg ～ 5.0×106/Kg; cells will be infused intravenously.</description>
      <arm_group_label>Anti-CD70 CAR-T cells</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1. Subject is≥18 years old (including cut-off value), gender is not limited. 2.&#xD;
               Histopathologically confirmed tumors of the urinary system (including renal cancers&#xD;
               and urothelial cancers). Renal cancers should have failed after targeted therapy&#xD;
               and/or immunotherapy. Urothelial cancers should have failed after chemotherapy and/or&#xD;
               immunotherapy. Or subjects are unable to tolerate or lack effective therapies.&#xD;
  &#xD;
               3. At least one measurable lesion according to RECIST v1.1. 4. CD70 should be positive&#xD;
               confirmed by Immunohistochemistry/Immunocytochemistry/ Flow Cytometry (IHC/ICC/FCM) in&#xD;
               tumor tissue samples.&#xD;
  &#xD;
               5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Life&#xD;
               expectancy ≥ 3 months. 7. Adequate function defined as: Hematological functions:&#xD;
               Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (Patients should not receive G-CSF&#xD;
               support within 7 days before laboratory examination); Absolute Lymphocyte Count (ALC)&#xD;
               ≥ 0.5 × 109/L; Hemoglobin (HGB) ≥ 80 g/L (Patients should not be transfused red cells&#xD;
               within 7 days before the laboratory examination); Platelet count (PLT) ≥ 75 × 109/L&#xD;
               (Patients should not receive transfusion support within 7 days before the laboratory&#xD;
               examination).&#xD;
  &#xD;
          Hepatic functions: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤&#xD;
          3.0 × upper limit of normal (ULN); AST and ALT of patients with liver metastasis ≤ 5 × ULN;&#xD;
          Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with liver metastasis must ≤ 3.0 ×&#xD;
          ULN; TBIL of patients with Gilbert's Syndrome ≤ 3.0 × ULN and Direct bilirubin (DBIL) ≤ 1.5&#xD;
          × ULN.&#xD;
  &#xD;
          Coagulation functions: International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial&#xD;
          thromboplastin time (APTT) ≤ 1.5 × ULN (Except for patients who are receiving therapeutic&#xD;
          anticoagulants.).&#xD;
  &#xD;
          Renal functions: Serum creatinine (Cr) ≤ 1.5 × ULN; or Estimated glomerular filtration rate&#xD;
          (eGFR) ≥30ml/(min·1.73 m2)(Calculated by CKD⁃EPI).&#xD;
  &#xD;
          Cardiac functions: Left ventricular ejection fraction (LVEF) &gt; 50%; Pulmonary function:&#xD;
          Oxygen saturation (SpO2) &gt; 92%. 8. Female participants of childbearing potential must&#xD;
          undergo a pregnancy test and the results must be negative. Female participants of&#xD;
          childbearing potential or male participants whose sex partner has childbearing potential&#xD;
          must be willing to use effective methods of contraception from screening period to at least&#xD;
          1 year after infusion.&#xD;
  &#xD;
          9. Participants must be able to understand the protocol and be willing to enroll the study,&#xD;
          sign the informed consent, and be able to comply with the study and follow-up procedures.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1. Patients have received systemic therapy with cytotoxic chemicals, monoclonal&#xD;
               antibodies, or immunotherapy within 4 weeks or 5 half-lives (which is shorter) prior&#xD;
               to signing informed consent; Patients have received systemic glucocorticoids&#xD;
               (prednisone at a dose of ≥10 mg per day or equivalent) or other immune-suppressive&#xD;
               therapy within 2 weeks prior to signing informed consent; Patients have received&#xD;
               systemic antitumor therapy with a biologic agent or other approved targeted&#xD;
               small-molecule inhibitor within 1 week or five half-lives (which is shorter) prior to&#xD;
               signing informed consent; Patients have received Chinese herbal medicine or Chinese&#xD;
               patent medicine with anti-tumor indication within 1 week prior to signing informed&#xD;
               consent.&#xD;
  &#xD;
               2. Pregnant or lactating women. 3. Patients with hepatitis B surface antigen (HBsAg)&#xD;
               positive. Patients who is hepatitis B core antibody (HBcAb) positive and the&#xD;
               quantification of HBV DNA in peripheral blood is higher than the lower limit of&#xD;
               detection. Patients who is hepatitis C virus (HCV) antibody positive and&#xD;
               quantification of HCV DNA in peripheral blood is higher than the lower limit of&#xD;
               detection. Patients with human immunodeficiency virus (HIV) antibody positive.&#xD;
               Patients with syphilis antibody positive and tolulized red unheated serum test (TRUST)&#xD;
               titer ≥ 1:4.&#xD;
  &#xD;
               4. The toxicities caused by the prior therapy (surgery, chemotherapy, radiotherapy,&#xD;
               targeted therapy, immunotherapy, etc.) have not recovered to grade 1 according to&#xD;
               CTCAE, except for hair loss and peripheral sensory nerve disorders.&#xD;
  &#xD;
               5. Have received any allogeneic tissue/organ transplantation (including bone marrow&#xD;
               transplantation, stem cell transplantation, liver transplantation, kidney&#xD;
               transplantation), except for the transplantation that does not require&#xD;
               immunosuppressive therapy (such as: corneal transplantation, hair transplantation.) 6.&#xD;
               Patients have received anti-CD70 CAR-T cell therapy. 7. Patients who have history of&#xD;
               major surgery and unrecovered severe trauma within 4 weeks prior to signing informed&#xD;
               consent; or plan to have major surgery within 12 weeks of cell therapy.&#xD;
  &#xD;
               8. Presence of known central nervous system metastases, but the following patients&#xD;
               will be allowed: a) Asymptomatic brain metastases; b) Clinically stable (no&#xD;
               radiographic progression within 4 weeks before apheresis and return of any neurologic&#xD;
               symptoms to baseline), and with no need for corticosteroids or other treatment for&#xD;
               brain metastases for ≥ 4 weeks.&#xD;
  &#xD;
               9. Patients with clinically significant systemic disease (such as: severe active&#xD;
               infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ&#xD;
               dysfunction) that evaluated by the investigator would impair the patients' ability to&#xD;
               tolerate the treatments used in this study or significantly increase the risk of&#xD;
               complications.&#xD;
  &#xD;
                 -  Uncontrolled severe active infection (sepsis, bacteremia, viremia, etc.);&#xD;
  &#xD;
                 -  Congestive heart failure with New York Heart Association (NYHA) functional class&#xD;
                    &gt; 1;&#xD;
  &#xD;
                 -  Clinically significant severe aortic stenosis and symptomatic mitral stenosis;&#xD;
  &#xD;
                 -  Electrocardiogram QTc &gt; 450 msec or QTc &gt; 480 msec in patients with bundle-branch&#xD;
                    block;&#xD;
  &#xD;
                 -  Uncontrolled clinically significant arrhythmia within 6 months prior to signing&#xD;
                    informed consent;&#xD;
  &#xD;
                 -  Acute coronary syndrome (such as: unstable angina, myocardial infarction) within&#xD;
                    6 months prior to signing informed consent;&#xD;
  &#xD;
                 -  Drug-uncontrolled hypertension (systolic pressure ≥ 160 mmHg and/or diastolic&#xD;
                    pressure ≥ 100 mmHg) or pulmonary hypertension;&#xD;
  &#xD;
                 -  Cerebrovascular accident occurred within 6 months prior to signing informed&#xD;
                    consent, including transient ischemic attack (TIA), cerebral infarction, cerebral&#xD;
                    hemorrhage, subarachnoid hemorrhage;&#xD;
  &#xD;
                 -  A history of active, chronic, or recurrent (within 1 year prior to signing&#xD;
                    informed consent) severe autoimmune disease or immune-mediated disease requiring&#xD;
                    steroids or other immunosuppressive therapy, including but not limited to&#xD;
                    systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel&#xD;
                    disease, Hashimoto's thyroiditis, autoimmune thyroid disease, multiple sclerosis.&#xD;
                    Exceptions: hypothyroidism that can be controlled only by hormone replacement&#xD;
                    therapy, skin diseases (such as: vitiligo, psoriasis) that do not require&#xD;
                    systemic treatment, coeliac disease that has been controlled; 10. Any form of&#xD;
                    primary or secondary immunodeficiency, such as severe combined immunodeficiency&#xD;
                    (SCID); 11. History of severe systemic hypersensitivity reaction to the&#xD;
                    drugs/ingredients [fludarabine, cyclophosphamide, dimethyl sulfoxide (DMSO), low&#xD;
                    molecular dextran, human serum albumin (HSA), etc.] used in this study.&#xD;
  &#xD;
                    12. Patients have received attenuated vaccine within 4 weeks prior to signing&#xD;
                    informed consent.&#xD;
  &#xD;
                    13. Patients have received other clinical trials within 4 weeks prior to signing&#xD;
                    informed consent.&#xD;
  &#xD;
                    14. History of another malignancy tumor within the previous five years, except&#xD;
                    for adequately treated non-melanoma skin cancer, carcinoma in situ of bladder,&#xD;
                    stomach, colon, cervix/dysplasia, melanoma, or breast.&#xD;
  &#xD;
                    15. History of neuropsychiatric diseases diagnosed by the ICD-11 criteria or&#xD;
                    evaluated by investigator, including but not limited to epilepsy, schizophrenia,&#xD;
                    dementia, drug and alcohol addictions.&#xD;
  &#xD;
                    16. For any other reasons, the patients are believed not suitable for&#xD;
                    participation in this study by investigators.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Linhui Wang</last_name>
      <role>Principal Investigator</role>
      <affiliation>Changhai Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yewei Bao</last_name>
      <phone>13612400566</phone>
      <email>16ywbao@alumni.stu.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Changhai Hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yewei Bao</last_name>
        <phone>13612400566</phone>
        <email>16ywbao@alumni.stu.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Anti-CD70 CAR-T</keyword>
    <keyword>Urologic Neoplasms</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Urologic Neoplasms</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/NCT05990621
  org study id: Anti-CD70 CAR-T Cell Injection
  nct id: NCT05990621
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-arm, open-label, exploratory clinical study to evaluate the safety,
        tolerability and preliminary efficacy of Anti-CD70 CAR-T cell injection in patients with
        CD70-positive Advanced Urologic Neoplasms.
  This study will include two parts, dose escalation phase (accelerated titration and 3+3
        design) followed by a dose expansion phase. All eligible participants will receive a
        conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by CAR-T cell
        injection.
  
        The dose escalation phase will determine the maximum tolerated dose (MTD) of Anti-CD70 CAR-T
        cell injection. Additional patients will be enrolled in the dose expansion phase to further
        characterize the safety profile and evaluate the efficacy of Anti-CD70 CAR-T cell injection,
        and establish recommended phase 2 dose (RP2D).
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Accelerated titration and 3+3 design dose escalation phase followed by dose expansion phase
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Adverse Events (AEs)
  time frame: 2 years
  description: Incidence and severity of adverse events.
  measure: Serious Adverse Events (SAEs)
  time frame: 2 years
  description: Incidence and severity of serious adverse events.
  measure: Adverse Events of Special Interest (AESI)
  time frame: 2 years
  description: Incidence and severity of adverse event of special interest.
  measure: Identification of Maximum Tolerated Dose (MTD)
  time frame: 4 weeks after the CAR-T cells infusion
  description: Incidence and severity of dose-limiting toxicities (DLTs) following infusion of UCL70802 cell injection, at each dose level tested in dose escalation phase.
  measure: Objective Response Rate (ORR)
  time frame: 2 years
  description: The Objective Response Rate (ORR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.
  measure: Duration of Overall Response (DOR)
  time frame: 2 years
  description: Time from documentation of disease response to disease progression.
  measure: Progression-Free Survival (PFS)
  time frame: 2 years
  description: PFS is defined as the time from CAR-T infusion to the date of the disease progression or death from any cause.
  measure: Overall Survival (OS)
  time frame: 2 years
  description: OS is defined as the time from CAR-T infusion to the date of death due to any cause.
  measure: Bio-distribution of Anti-CD70 CAR-T cells
  time frame: 2 years
  description: CAR copies will be measured by qPCR to evaluate the expansion and persistence of CAR-T cells in vivo.
  measure: Cytokine Level in Peripheral Blood
  time frame: 2 years
  description: Level of cytokines (IFN-γ, IL-6, IL-2, etc.) in serum.
  measure: Number of participants with anti-drug antibodies.
  time frame: 2 years
  arm group label: Anti-CD70 CAR-T cells
  arm group type: Experimental
  description: Anti-CD70 CAR-T cells are autologous genetically modified T cells.
  intervention type: Biological
  intervention name: Anti-CD70 CAR-T cells
  description: 0.6×106/Kg ～ 5.0×106/Kg; cells will be infused intravenously.
  arm group label: Anti-CD70 CAR-T cells
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Linhui Wang
  role: Principal Investigator
  affiliation: Changhai Hospital
  last name: Yewei Bao
  phone: 13612400566
  email: 16ywbao@alumni.stu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Urologic Neoplasms