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/NCT06006403</url>
    </required_header>
    <id_info>
      <org_study_id>PBC050</org_study_id>
      <nct_id>NCT06006403</nct_id>
    </id_info>
    <brief_title>Safety and Efficacy of CD123-targeted CAR-NK for Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm</brief_title>
    <official_title>Clinical Study of Targeting CD123 Chimeric Antigen Receptor Natural Killer Cells (CAR-NK) in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chongqing Precision Biotech Co., Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Shanxi Bethune Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Chongqing Precision Biotech 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>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study is a single-arm, open-label, dose-escalating + dose-expansion clinical study,&#xD;
        aiming to evaluate the safety and efficacy of targeting CD123 CAR-NK cell preparations in&#xD;
        Relapsed/refractory acute myeloid leukemia (AML) or blastocytic plasmacytoid dendritic cell&#xD;
        neoplasm (BPDCN). The pharmacokinetic characteristics of CAR-NK cell preparations for the&#xD;
        treatment of patients with Relapsed/refractory acute myeloid leukemia or blastocytic&#xD;
        plasmacytoid dendritic cell neoplasm were obtained and the recommended dose.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        According to the different disease type, it is divided into two subgroups: AML and BPDCN.&#xD;
        Each subgroup includes a dose exploration stage (Part A) and a dose expansion stage (Part B).&#xD;
        3 patients were explored, starting from the low-dose group, and in the dose expansion phase,&#xD;
        the safety and efficacy were further verified according to the safe recommended dose obtained&#xD;
        in the dose exploration phase.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">August 31, 2023</start_date>
    <completion_date type="Anticipated">August 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>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To evaluate the safety of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Safety and Tolerability]</measure>
      <time_frame>1 month</time_frame>
      <description>The incidence of adverse events after CD123 CAR-NK cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>To evaluate the efficacy of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]</measure>
      <time_frame>1month,3months</time_frame>
      <description>Objective response rate at 4W±7D and 3M±7D after CAR-NK infusion (Objective response rate includes CR, CRi)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>AUCS of CD123 CAR-NK cells [Cell dynamics]</measure>
      <time_frame>3 months</time_frame>
      <description>AUCS is defined as the area under the curve in 90 days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CMAX of CD123 CAR-NK cells [Cell dynamics]</measure>
      <time_frame>3 months</time_frame>
      <description>CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TMAX of CD123 CAR-NK cells[Cell dynamics]</measure>
      <time_frame>3 months</time_frame>
      <description>TMAX is defined as the time to reach the highest concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacodynamics of CD123 CAR-NK cells[Cell dynamics]</measure>
      <time_frame>3 months</time_frame>
      <description>The degree of clearance of malignant cells in peripheral blood was detected by blood smear at each time point，and the concentration level of serum cytoplasmic factors such as CRP and IL-6 were detected by ELISA at each time point</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Duration of Response (DOR) of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]</measure>
      <time_frame>2 years</time_frame>
      <description>DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause</description>
    </other_outcome>
    <other_outcome>
      <measure>Progress-free survival(PFS) of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]</measure>
      <time_frame>2 years</time_frame>
      <description>PFS will be assessed from the first CD123 CAR-NK cell infusion to death from any cause or the first assessment of progression</description>
    </other_outcome>
    <other_outcome>
      <measure>Overall survival(OS)of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]</measure>
      <time_frame>2 years</time_frame>
      <description>OS will be assessed from the first CD123 CAR-NK cell infusion to death from any cause</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)</condition>
    <condition>Relapse Leukemia</condition>
    <condition>Refractory Leukemia</condition>
    <arm_group>
      <arm_group_label>Acute Myeloid Leukemia</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Infusion of CD123-targeted CAR-NK cells by dose of 1-10x10^6 cells/kg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Blastic Plasmacytoid Dendritic Cell Neoplasm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Infusion of CD123-targeted CAR-NK cells by dose of 1-10x10^6 cells/kg</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>CD123 targeted CAR-NK cells</intervention_name>
      <description>Administration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.</description>
      <arm_group_label>Acute Myeloid Leukemia</arm_group_label>
      <arm_group_label>Blastic Plasmacytoid Dendritic Cell Neoplasm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Gender is not limited, age 18-75 years old (including the threshold value);&#xD;
  &#xD;
            2. The expression of CD123 in tumor cells was detected by flow cytometry.&#xD;
  &#xD;
            3. Patients with relapsed/refractory AML or BPDCN diagnosed with CD123 positive: 1) AML:&#xD;
               a. Recurrent: After complete response (CR), the recurrence of leukemia cells in&#xD;
               peripheral blood or bone marrow original cells ≥5% (except for other reasons such as&#xD;
               bone marrow regeneration after consolidation chemotherapy) or the occurrence of&#xD;
               extramedullary leukemia cell infiltration; b. Refractory: refers to those who have&#xD;
               failed to receive 2 courses of treatment with standard protocols; Patients recurrence&#xD;
               within 12 months after CR with consolidation and intensive treatment; Recurrence after&#xD;
               12 months but failed to respond to conventional chemotherapy; 2 or more relapses;&#xD;
               Extramedullary leukemia persists;&#xD;
  &#xD;
          2) BPDCN: has failed to receive guidelines-recommended salvage therapy or is unable to&#xD;
          tolerate current therapy, and has persistent or recurrent disease in any of the peripheral&#xD;
          blood, bone marrow, lymph nodes, spleen, skin lesions, or other site lesions.&#xD;
  &#xD;
          4. Expected survival time is more than 12 weeks;&#xD;
  &#xD;
          5. ECOG 0-2 points (Appendix 2);&#xD;
  &#xD;
          6. No serious mental disorders; The functions of important organs are basically normal:&#xD;
  &#xD;
            1. Cardiac function: echocardiography indicated cardiac ejection fraction ≥50%, and no&#xD;
               obvious abnormality was found in electrocardiogram;&#xD;
  &#xD;
            2. Renal function: serum creatinine ≤2.0×ULN;&#xD;
  &#xD;
            3. Liver function: ALT and AST ≤ 3.0×ULN;&#xD;
  &#xD;
            4. Total bilirubin and alkaline phosphatase ≤ 2.0×ULN (Gilbert syndrome ≤ 3.0×ULN);&#xD;
  &#xD;
            5. Blood oxygen saturation &amp;gt; 92%.&#xD;
  &#xD;
               7. The patient or his/her guardian agrees to participate in the clinical trial and&#xD;
               signs the ICF, indicating that he/she understands the purpose and procedure of the&#xD;
               clinical trial and is willing to participate in the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Prior to screening, the following anti-tumor therapies were received: chemotherapy,&#xD;
               targeted therapy, or other investigational drug treatment within 14 days or at least 5&#xD;
               half-lives (whichever is shorter), except in cases where disease progression has been&#xD;
               confirmed after treatment;&#xD;
  &#xD;
            2. had a cerebrovascular accident or seizure within 6 months before signing the ICF;&#xD;
  &#xD;
            3. There is an active or uncontrolled infection that requires systemic treatment within 1&#xD;
               week prior to screening;&#xD;
  &#xD;
            4. suffering from any of the following heart diseases:&#xD;
  &#xD;
                 1. New York Heart Association (NYHA) Stage III or IV congestive heart failure;&#xD;
  &#xD;
                 2. Had myocardial infarction or coronary artery bypass grafting (CABG) within ≤6&#xD;
                    months before enrollment;&#xD;
  &#xD;
                 3. A history of clinically significant ventricular arrhythmia, or unexplained&#xD;
                    syncope (other than those caused by vasovagal or dehydration);&#xD;
  &#xD;
                 4. History of severe non-ischemic cardiomyopathy;&#xD;
  &#xD;
            5. combined with active hepatitis B;&#xD;
  &#xD;
            6. Combined with active autoimmune diseases, long-term immunosuppressive therapy is&#xD;
               required;&#xD;
  &#xD;
            7. have other malignancies, except for adequately treated cervical carcinoma in situ,&#xD;
               basal cell or squamous cell skin cancer, local prostate cancer after radical surgery,&#xD;
               and ductal carcinoma in situ after radical surgery;&#xD;
  &#xD;
            8. Had received live attenuated vaccine within 4 weeks prior to screening;&#xD;
  &#xD;
            9. Women who are pregnant or breastfeeding, and male or female subjects who plan to have&#xD;
               a family within 1 year after receiving CAR T cell transfusion;&#xD;
  &#xD;
           10. Circumstances deemed unsuitable for participation in the study by other researchers.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jia Wei, M.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shanxi Bethune Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jia Wei, M.D</last_name>
      <phone>13986102084</phone>
      <email>jiawei@tjh.tjmu.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shanxi Bethune Hospital</name>
        <address>
          <city>Taiyuan</city>
          <state>Shanxi</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jia Wei, MD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 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>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Leukemia, Myeloid</mesh_term>
      <mesh_term>Leukemia, Myeloid, Acute</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/NCT06006403
  org study id: PBC050
  nct id: NCT06006403
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study is a single-arm, open-label, dose-escalating + dose-expansion clinical study,
        aiming to evaluate the safety and efficacy of targeting CD123 CAR-NK cell preparations in
        Relapsed/refractory acute myeloid leukemia (AML) or blastocytic plasmacytoid dendritic cell
        neoplasm (BPDCN). The pharmacokinetic characteristics of CAR-NK cell preparations for the
        treatment of patients with Relapsed/refractory acute myeloid leukemia or blastocytic
        plasmacytoid dendritic cell neoplasm were obtained and the recommended dose.
  According to the different disease type, it is divided into two subgroups: AML and BPDCN.
        Each subgroup includes a dose exploration stage (Part A) and a dose expansion stage (Part B).
        3 patients were explored, starting from the low-dose group, and in the dose expansion phase,
        the safety and efficacy were further verified according to the safe recommended dose obtained
        in the dose exploration phase.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To evaluate the safety of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Safety and Tolerability]
  time frame: 1 month
  description: The incidence of adverse events after CD123 CAR-NK cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)
  measure: To evaluate the efficacy of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
  time frame: 1month,3months
  description: Objective response rate at 4W±7D and 3M±7D after CAR-NK infusion (Objective response rate includes CR, CRi)
  measure: AUCS of CD123 CAR-NK cells [Cell dynamics]
  time frame: 3 months
  description: AUCS is defined as the area under the curve in 90 days
  measure: CMAX of CD123 CAR-NK cells [Cell dynamics]
  time frame: 3 months
  description: CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood
  measure: TMAX of CD123 CAR-NK cells[Cell dynamics]
  time frame: 3 months
  description: TMAX is defined as the time to reach the highest concentration
  measure: Pharmacodynamics of CD123 CAR-NK cells[Cell dynamics]
  time frame: 3 months
  description: The degree of clearance of malignant cells in peripheral blood was detected by blood smear at each time point，and the concentration level of serum cytoplasmic factors such as CRP and IL-6 were detected by ELISA at each time point
  measure: Duration of Response (DOR) of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
  time frame: 2 years
  description: DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause
  measure: Progress-free survival(PFS) of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
  time frame: 2 years
  description: PFS will be assessed from the first CD123 CAR-NK cell infusion to death from any cause or the first assessment of progression
  measure: Overall survival(OS)of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
  time frame: 2 years
  description: OS will be assessed from the first CD123 CAR-NK cell infusion to death from any cause
  arm group label: Acute Myeloid Leukemia
  arm group type: Experimental
  description: Infusion of CD123-targeted CAR-NK cells by dose of 1-10x10^6 cells/kg
  arm group label: Blastic Plasmacytoid Dendritic Cell Neoplasm
  arm group type: Experimental
  description: Infusion of CD123-targeted CAR-NK cells by dose of 1-10x10^6 cells/kg
  intervention type: Biological
  intervention name: CD123 targeted CAR-NK cells
  description: Administration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
  arm group label: Acute Myeloid Leukemia
  arm group label: Blastic Plasmacytoid Dendritic Cell Neoplasm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jia Wei, M.D
  role: Principal Investigator
  affiliation: Shanxi Bethune Hospital
  last name: Jia Wei, M.D
  phone: 13986102084
  email: jiawei@tjh.tjmu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Neoplasms
  mesh term: Leukemia, Myeloid
  mesh term: Leukemia, Myeloid, Acute