<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/NCT03796390</url>
  </required_header>
  <id_info>
    <org_study_id>Daopei CD123CAR-T</org_study_id>
    <nct_id>NCT03796390</nct_id>
  </id_info>
  <brief_title>Study Evaluating Safety and Efficacy of CAR-T Cells Targeting CD123 in Patients With Acute Myelocytic Leukemia</brief_title>
  <official_title>Study Evaluating Safety and Efficacy of CAR-T Cells Targeting CD123 in Patients With Acute Myelocytic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hebei Senlang Biotechnology Inc., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hebei Yanda Ludaopei Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hebei Senlang Biotechnology Inc., Ltd.</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 an open, single-arm, phase I clinical study to evaluate efficacy and safety of&#xD;
      chimeric antigen receptor T cell immunotherapy (CAR-T) targeting CD123 in the treatment of&#xD;
      Acute Myelocytic Leukemia. A total of 15 patients are planned to be enrolled following up one&#xD;
      year.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated&#xD;
      unprecedented successes in treating patients with hematopoietic and lymphoid malignancies.&#xD;
      Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may be potential in&#xD;
      developing the corresponding CAR-T cells to treat patients whose tumors expressing those&#xD;
      markers. In this study, investigators will evaluate the safety and efficacy of CAR-T&#xD;
      targeting CD123 in patients with Acute Myelocytic Leukemia. The primary goal is safety&#xD;
      assessment including cytokine storm response and any other adverse effects. In addition,&#xD;
      disease status after treatment will also be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 26, 2018</start_date>
  <completion_date type="Anticipated">June 6, 2021</completion_date>
  <primary_completion_date type="Anticipated">November 6, 2020</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>Tumor load</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CAR-T cell persistence</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>CAR-T cell persistence will be quantified with flow cytometry and qPCR； Percentage of CART cells in BM and copies of car per ug DNA</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Acute Myelocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>CD123 CAR-T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be be treated with CD123 CAR-T cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD123 CAR-T cells</intervention_name>
    <description>Patients will be drawn 50-100 ml blood to obtain enough peripheral blood mononuclear cells (PBMC) for CAR-T manufacturing. The T cells will be purified from the PBMC, transduced with CAR lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy will then be given. Following tumor burden reassessment, CD123 CAR-T cells will be infused.</description>
    <arm_group_label>CD123 CAR-T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with acute myeloid leukemia who voluntarily signed informed consent and met&#xD;
             the following criteria:&#xD;
&#xD;
               1. Diagnosed as recurrent or refractory acute myeloid leukemia&#xD;
&#xD;
               2. Tumor cells confirmed CD123 positive by Flow cytometry (FCM) or&#xD;
                  immunohistochemical detection, and CD123 positive rate &gt;80%&#xD;
&#xD;
               3. Age ≥ 2 years old, and &lt;65 years old&#xD;
&#xD;
               4. Estimated survival time is longer than 3 months from the date of signing the&#xD;
                  informed consent form&#xD;
&#xD;
               5. KPS ≥ 80 points&#xD;
&#xD;
               6. Important organs function need to meet the following conditions:&#xD;
&#xD;
             1) EF&gt;50%, and there is no obvious abnormality in ECG; 2) SpO2≥90%; 3)Cr≤2.5ULN; 4)ALT&#xD;
             and AST≤4ULN, TBil≤50μmol/L 7. Subjects with a pregnancy plan must agree to take&#xD;
             contraception before the enrollment study and after the study lasts for six months; if&#xD;
             the subject is pregnant or suspects of pregnancy, the investigator should be notified&#xD;
             immediately 8. Need to stop chemotherapy for at least 2 weeks before collecting the&#xD;
             blood to manufacture CAR-T cells.&#xD;
&#xD;
             9. For allogeneic hematopoietic stem cell transplantation subjects, it is necessary to&#xD;
             stop the immunosuppressant against GVHD for at least 2 weeks before collecting&#xD;
             autologous blood preparation, and if the donor is preparing blood, it is of no&#xD;
             influence; 10. If the subject has a history of central nervous system (CNS) leukemia,&#xD;
             the tumor cells in the cerebrospinal fluid need to be cleared and the white blood cell&#xD;
             count &lt;5 * 10^6 / L ,then can proceed lymphodepletion 11. Subjects who participate in&#xD;
             other studies must withdraw other studies for 2 weeks before they can be enrolled.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Combine other diseases not effectively controlled, including but not limited to&#xD;
             persistent or poorly controlled infections, symptomatic congestive heart failure,&#xD;
             unstable angina, arrhythmia, poorly controlled lung disease or mental illness&#xD;
&#xD;
          2. There are other active malignant tumors&#xD;
&#xD;
          3. Combined serious infection and can not be effectively controlled&#xD;
&#xD;
          4. Active hepatitis (HBV DNA or hepatitis C virus ribonucleic acid [HCVRNA] detection&#xD;
             positive)&#xD;
&#xD;
          5. Human immunodeficiency virus (HIV) infection or syphilis infection&#xD;
&#xD;
          6. Have a history of severe allergies in biological products (including antibiotics)&#xD;
&#xD;
          7. One month after discontinuation of immunosuppressants, allogeneic hematopoietic stem&#xD;
             cell transplantation patients still have acute graft versus host response (GvHD)&#xD;
&#xD;
          8. Female subjects are pregnant or lactating&#xD;
&#xD;
          9. Systemic administration of glucocorticoids within one week prior to CAR-T treatment&#xD;
&#xD;
         10. In the past, there was a prolonged QT interval or severe heart disease.&#xD;
&#xD;
         11. Active autoimmune diseases requiring systemic immunosuppressive therapy&#xD;
&#xD;
         12. The investigator believes that it may increase the risk of the subject or interfere&#xD;
             with the study results.&#xD;
&#xD;
        Exit criteria：&#xD;
&#xD;
          1. The subjects request to withdraw from the study before CAR-T infusion&#xD;
&#xD;
          2. The subjects seriously violate the protocol&#xD;
&#xD;
          3. Before CAR-T infusion, the following indicators are still abnormal after treatment:&#xD;
&#xD;
        1) EF&gt;50%, and there is no obvious abnormality in ECG 2) SpO2≥90% 3)Cr≤2.5ULN(the upper&#xD;
        limit of normal ) 4) ALT and AST ≤ 4ULN, TBil ≤ 50μmol / L 4.Not enough T cells for&#xD;
        manufacture standard CAR-T cells 5. Other serious adverse events occurred&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peihua Lu, PhD&amp;MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hebei Yanda Ludaopei Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peihua Lu, PhD&amp;MD</last_name>
    <phone>008618611636172</phone>
    <email>peihua_lu@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jianqiang Li, PhD&amp;MD</last_name>
    <phone>008615511369555</phone>
    <email>limmune@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hebei Yanda Ludaopei Hospital</name>
      <address>
        <city>Langfang</city>
        <state>Hebei</state>
        <zip>065000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peihua Lu, PhD&amp;MD</last_name>
      <phone>008618611636172</phone>
      <email>peihua_lu@126.com</email>
    </contact>
    <investigator>
      <last_name>Peihua Lu, PhD&amp;MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jianqiang Li, PhD&amp;MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>January 9, 2019</last_update_submitted>
  <last_update_submitted_qc>January 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AML，CD123</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</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>


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/NCT03796390
org study id: Daopei CD123CAR-T
nct id: NCT03796390
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is an open, single-arm, phase I clinical study to evaluate efficacy and safety of
      chimeric antigen receptor T cell immunotherapy (CAR-T) targeting CD123 in the treatment of
      Acute Myelocytic Leukemia. A total of 15 patients are planned to be enrolled following up one
      year.
Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated
      unprecedented successes in treating patients with hematopoietic and lymphoid malignancies.
      Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may be potential in
      developing the corresponding CAR-T cells to treat patients whose tumors expressing those
      markers. In this study, investigators will evaluate the safety and efficacy of CAR-T
      targeting CD123 in patients with Acute Myelocytic Leukemia. The primary goal is safety
      assessment including cytokine storm response and any other adverse effects. In addition,
      disease status after treatment will also be evaluated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Tumor load
time frame: Up to 12 months
description: Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.
measure: CAR-T cell persistence
time frame: Up to 12 months
description: CAR-T cell persistence will be quantified with flow cytometry and qPCR； Percentage of CART cells in BM and copies of car per ug DNA
arm group label: CD123 CAR-T cells
arm group type: Experimental
description: Patients will be be treated with CD123 CAR-T cells
intervention type: Biological
intervention name: CD123 CAR-T cells
description: Patients will be drawn 50-100 ml blood to obtain enough peripheral blood mononuclear cells (PBMC) for CAR-T manufacturing. The T cells will be purified from the PBMC, transduced with CAR lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy will then be given. Following tumor burden reassessment, CD123 CAR-T cells will be infused.
arm group label: CD123 CAR-T cells
criteria: 
gender: All
minimum age: 2 Years
maximum age: 65 Years
healthy volunteers: No
last name: Peihua Lu, PhD&MD
role: Study Chair
affiliation: Hebei Yanda Ludaopei Hospital
last name: Peihua Lu, PhD&MD
phone: 008618611636172
email: peihua_lu@126.com
last name: Jianqiang Li, PhD&MD
phone: 008615511369555
email: limmune@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute