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/NCT06027853</url>
    </required_header>
    <id_info>
      <org_study_id>QH-CLL1-01</org_study_id>
      <nct_id>NCT06027853</nct_id>
    </id_info>
    <brief_title>Natural Killer(NK) Cell Therapy Targeting CLL1 in Acute Myeloid Leukemia</brief_title>
    <official_title>Clinical Study to Evaluate the Safety and Efficacy of iPSC NK Cells Targeting CLL1 in Patients With Relapsed/Refractory AML</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhejiang University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Hangzhou Qihangene Biotech Co.,Ltd.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Zhejiang University</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 phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the&#xD;
        safety, tolerability and preliminary efficacy of CLL1 target CAR iPSC NK cells in patients&#xD;
        with relapsed/refractory AML&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Acute myelogenous leukemia (AML) is a potentially cur-able disease; 70% of newly diagnosed&#xD;
        patients achievecomplete remission with first-line therapy, but prognosisworsens for relapsed&#xD;
        disease in both pediatric and adultpatients. CLL-1 has attracted the researchers' attention&#xD;
        due to its high expression in AML while being absent in normal hematopoietic stem cell.&#xD;
        Accumulating evidence have demonstrated CLL-1 is an ideal target for AML.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 10, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of Treatment-Emergent Adverse Events</measure>
      <time_frame>28 Days from first dose of iPSC NK cell infusion</time_frame>
      <description>Safety and Tolerability</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of subjects with Dose Limiting Toxicities within each dose level cohort</measure>
      <time_frame>28 Days from first dose of iPSC NK cell infusion</time_frame>
      <description>Tolerability</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Determination of the pharmacokinetics (PK) of iPSC NK cells in peripheral blood</measure>
      <time_frame>Up to approximately 2 years after last dose of iPSC NK cell infusion</time_frame>
      <description>The PK of iPSC NK in peripheral blood will be reported as the relative percentage of product DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">24</enrollment>
    <condition>AML, Adult</condition>
    <arm_group>
      <arm_group_label>CAR-NK cell therapy in Adult subjects with r/r AML</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>CAR-NK cell therapy in Adult subjects with r/r AML</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>CLL1 CAR-NK cell injection</intervention_name>
      <description>Drug: CLL1 NK cell therapy Drug: Cyclophosphamid Lympho-conditioning Agent Drug: Fludarabine Lympho-conditioning Agent&#xD;
  Drug: VP-16 Lympho-conditioning Agent</description>
      <arm_group_label>CAR-NK cell therapy in Adult subjects with r/r AML</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. ≥18 years old.&#xD;
  &#xD;
            2. Confirmed diagnosis of r/r AML&#xD;
  &#xD;
            3. CLL1 expression is positive in AML blasts.&#xD;
  &#xD;
            4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy&#xD;
               greater than 12 weeks.&#xD;
  &#xD;
            5. Adequate organ and marrow function, as defined below:&#xD;
  &#xD;
                 1. Blood creatinine (Cr) ≤ 2 x ULN or calculated creatinine clearance (Cockcroft-&#xD;
                    Gault formula) ≥ 50 mL/min;&#xD;
  &#xD;
                 2. Total bilirubin (TBIL) ≤ 2 x the ULN;&#xD;
  &#xD;
                 3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;&#xD;
  &#xD;
                 4. International normalized ratio (INR) and activated partial thromboplastin time&#xD;
                    (aPTT) ≤ 1.5 x ULN&#xD;
  &#xD;
            6. Females of childbearing potential must have a negative serum pregnancy test.&#xD;
  &#xD;
            7. Donor specific antibody (DSA) is negative: MFI &lt;= 2000.&#xD;
  &#xD;
            8. Provision of signed and dated informed consent form (ICF).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Allergic to drug used in this study.&#xD;
  &#xD;
            2. Subjects received any antitumor therapy as follows, prior to first NK infusion:&#xD;
  &#xD;
                 1. Systemic steroid therapy within 3 days (except physiological replacement&#xD;
                    therapy);&#xD;
  &#xD;
                 2. Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is&#xD;
                    less;&#xD;
  &#xD;
                 3. Radiotherapy within 4 weeks;&#xD;
  &#xD;
                 4. Donor lymphocyte infusion within 6 weeks;&#xD;
  &#xD;
                 5. Intrathecal treatment within 1 week;&#xD;
  &#xD;
                 6. CAR-T therapy, CAR-NK therapy, or any other genetically modified cell therapy&#xD;
                    product within 6 months;&#xD;
  &#xD;
            3. History of allogeneic stem cell transplantation.&#xD;
  &#xD;
            4. Received the vaccine within 4 weeks prior to the first infusion and/or expected to&#xD;
               require vaccination from the study period to 12 weeks after the last infusion.&#xD;
  &#xD;
            5. Active central nervous system Leukemia.&#xD;
  &#xD;
            6. Acute Promyelocytic Leukemia (APL).&#xD;
  &#xD;
            7. History of other malignant tumors, except for those who have achieved complete&#xD;
               remission more than 5 years after radical treatment without any signs of recurrence.&#xD;
  &#xD;
            8. Active autoimmune diseases.&#xD;
  &#xD;
            9. History of central nervous system disease or meningeal involvement such as epilepsy,&#xD;
               paralysis, aphasia, stroke, etc.&#xD;
  &#xD;
           10. Serious cardiovascular and cerebrovascular diseases:&#xD;
  &#xD;
                 1. Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)≥480&#xD;
                    ms;&#xD;
  &#xD;
                 2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or&#xD;
                    other grade 3 or higher cardiovascular and cerebrovascular events within 6 months&#xD;
                    prior to first infusion;&#xD;
  &#xD;
                 3. New York Heart Association (NYHA) class II or above congestive heart failure or&#xD;
                    left ventricular ejection fraction (LVEF) &lt;50% in color Doppler echocardiography;&#xD;
  &#xD;
                 4. Hypertension that cannot be controlled by drug.&#xD;
  &#xD;
           11. Active pulmonary infection; SpO2 ≤90%; Pulmonary embolism, chronic obstructive&#xD;
               pulmonary disease, or interstitial lung disease.&#xD;
  &#xD;
           12. Uncontrolled bacterial, fungal, or viral infection. Known HIV infection, active&#xD;
               Hepatitis B (HBV) or Hepatitis C (HCV) infection.&#xD;
  &#xD;
           13. History of substance abuse.&#xD;
  &#xD;
           14. Toxicity induced by previous therapy not recovered to ≤ grade 2(NCI-CTCAE v5.0).&#xD;
  &#xD;
           15. Large surgical treatment within 4 weeks prior to first infusion, not including&#xD;
               diagnostic biopsy.&#xD;
  &#xD;
           16. Pregnant/breastfeeding women.&#xD;
  &#xD;
           17. Investigator-assessed presence of any medical or social issues that are likely to&#xD;
               interfere with study conduct or may cause increased risk to subject.&#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>He Huang, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>First Affiliated Hospital of Zhejiang University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>He Huang, MD</last_name>
      <phone>+8613605714822</phone>
      <email>hehuangyu@126.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Yongxian Hu, MD</last_name>
      <phone>+8615957162012</phone>
      <email>huyongxian2000@aliyun.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Clinical research ethics committee of the first affiliated hospital, college of medicine, zhejiang University</name>
        <address>
          <city>Hangzhou</city>
          <state>Zhejiang</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>He Huang</last_name>
        <phone>0571-87233772</phone>
        <email>hehuang@zju.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Zhejiang University</investigator_affiliation>
      <investigator_full_name>He Huang</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <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/NCT06027853
  org study id: QH-CLL1-01
  nct id: NCT06027853
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the
        safety, tolerability and preliminary efficacy of CLL1 target CAR iPSC NK cells in patients
        with relapsed/refractory AML
  Acute myelogenous leukemia (AML) is a potentially cur-able disease; 70% of newly diagnosed
        patients achievecomplete remission with first-line therapy, but prognosisworsens for relapsed
        disease in both pediatric and adultpatients. CLL-1 has attracted the researchers' attention
        due to its high expression in AML while being absent in normal hematopoietic stem cell.
        Accumulating evidence have demonstrated CLL-1 is an ideal target for AML.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Treatment-Emergent Adverse Events
  time frame: 28 Days from first dose of iPSC NK cell infusion
  description: Safety and Tolerability
  measure: Incidence of subjects with Dose Limiting Toxicities within each dose level cohort
  time frame: 28 Days from first dose of iPSC NK cell infusion
  description: Tolerability
  measure: Determination of the pharmacokinetics (PK) of iPSC NK cells in peripheral blood
  time frame: Up to approximately 2 years after last dose of iPSC NK cell infusion
  description: The PK of iPSC NK in peripheral blood will be reported as the relative percentage of product DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points
  arm group label: CAR-NK cell therapy in Adult subjects with r/r AML
  arm group type: Experimental
  description: CAR-NK cell therapy in Adult subjects with r/r AML
  intervention type: Drug
  intervention name: CLL1 CAR-NK cell injection
  description: Drug: CLL1 NK cell therapy Drug: Cyclophosphamid Lympho-conditioning Agent Drug: Fludarabine Lympho-conditioning Agent
  Drug: VP-16 Lympho-conditioning Agent
  arm group label: CAR-NK cell therapy in Adult subjects with r/r AML
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: He Huang, MD
  role: Principal Investigator
  affiliation: First Affiliated Hospital of Zhejiang University
  last name: He Huang, MD
  phone: +8613605714822
  email: hehuangyu@126.com
  last name: Yongxian Hu, MD
  phone: +8615957162012
  email: huyongxian2000@aliyun.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Zhejiang University
  investigator full name: He Huang
  investigator title: Professor
  sharing ipd: No