<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/NCT03275493</url>
  </required_header>
  <id_info>
    <org_study_id>UnicarTherapy201701</org_study_id>
    <nct_id>NCT03275493</nct_id>
  </id_info>
  <brief_title>Humanized CD19 CAR-T Cells With CRS Suppression Technology for r/r CD19+ Acute Lymphoblastic Leukemia</brief_title>
  <official_title>Humanized Chimeric Antigen Receptor T Cells Against CD19 With Cytokine Release Syndrome (CRS) Suppression Technology for Refractory/Relapsed CD19+ Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First Affiliated Hospital of Soochow University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Unicar-Therapy Bio-medicine Technology Co.,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 a single center,randomized ,two-cohorts, open-label ,phase 1/2 study to evaluate the&#xD;
      efficacy and safety of T cells expressing humanized CD19 chimeric antigen receptors treatment&#xD;
      for relapsed/refractory CD19+ acute lymphoblastic leukemia patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Relapsed/refractory CD19 + acute lymphoblastic leukemia patients were randomly enrolled in&#xD;
      this study to compare the efficacy and safety between two cohorts: 1. Humanized CD19 CAR-T&#xD;
      cells； 2. Humanized CD19 CAR-T cells with CRS suppression technology.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Anticipated">September 18, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 18, 2023</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of severe CRS</measure>
    <time_frame>30 days after infusion of humanized CD19 CAR-T cells</time_frame>
    <description>The safety of the humanized CD19 CAR-T cells treatment will be evaluated and the maximum tolerated dose will be determined</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response of humanized CD19 CAR-T cells treatment who achieve morphology complete remission(CR) and MRD negativity.</measure>
    <time_frame>30 days after infusion of humanized CD19 CAR-T cells</time_frame>
    <description>The efficacy of the humanized CD19 CAR-T cells infusion will be estimated based on the number of participants who have morphology complete remission(CR) and MRD negativity following the humanized CD19 CAR- T cells infusion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>CD19 Positive</condition>
  <condition>Relapse</condition>
  <condition>Refractory</condition>
  <arm_group>
    <arm_group_label>Experimental: Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This cohort will determine the safety and efficacy of humanized CD19 CAR-T cells for CD19+ acute lymphoblastic leukemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental: Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This cohort will determine the safety and efficacy of humanized CD19 CAR-T cells with CRS suppression technology for CD19+ acute lymphoblastic leukemia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Humanized CD19 CAR-T cells</intervention_name>
    <description>Express a Second Generation 4-1BB:humanized CD19 CAR-T cells</description>
    <arm_group_label>Experimental: Cohort 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Humanized CD19 CAR-T cells with CRS suppression technology</intervention_name>
    <description>Express a Second Generation 4-1BB:humanized CD19 CAR-T cells with CRS suppression technology</description>
    <arm_group_label>Experimental: Cohort 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 6 to 65&#xD;
&#xD;
          2. Voluntary informed consent is given&#xD;
&#xD;
          3. Expected survival ≥12 weeks&#xD;
&#xD;
          4. Relapsed or refractory CD19+ acute leukemia, ineligible for allo-HSCT,or relapse after&#xD;
             auto-HSCT&#xD;
&#xD;
          5. Organ function: (1)Left ventricular ejection fractions≥ 0.6 by echocardiography (2)ALT&#xD;
             ≤3 times of ULN, or bilirubin &lt;2.0 mg/dl (3)Creatinine &lt; 2 mg/dl and less than 2.5 ×&#xD;
             normal for age (4)Prothrombin time and activated partial thromboplastin time &lt; 2 times&#xD;
             of ULN (5)Arterial oxygen saturation&gt; 92%&#xD;
&#xD;
          6. Karnofsky score ≥ 60 ;&#xD;
&#xD;
          7. No history of combined chemotherapy in the recent 1 month and no immunotherapy in the&#xD;
             recent 3 months;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Uncontrolled active infections&#xD;
&#xD;
          2. Active hepatitis B or hepatitis C infection&#xD;
&#xD;
          3. HIV infection&#xD;
&#xD;
          4. History of myocardio infarction in the past 6 months, or history of severe arrhythmia&#xD;
&#xD;
          5. Congenital immunodeficiency&#xD;
&#xD;
          6. Pregnant or lactating women&#xD;
&#xD;
          7. History or presence of clinically relevant CNS pathology such as epilepsy, generalized&#xD;
             seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia,&#xD;
             Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis&#xD;
&#xD;
          8. Previous treatment with any gene therapy products&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiaowen Tang, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affiliated Hospital of Soochow University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiaowen Tang, PhD</last_name>
    <phone>8651267781525</phone>
    <email>tangxiaowen@suda.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lei Yu, PhD</last_name>
    <phone>8613818629089</phone>
    <email>ylyh188@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The first affiliated hospital of soochow university</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <zip>200000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shengli Xue, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>May 18, 2022</last_update_submitted>
  <last_update_submitted_qc>May 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CD19+ ,CAR-T, CRS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</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/NCT03275493
org study id: UnicarTherapy201701
nct id: NCT03275493
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a single center,randomized ,two-cohorts, open-label ,phase 1/2 study to evaluate the
      efficacy and safety of T cells expressing humanized CD19 chimeric antigen receptors treatment
      for relapsed/refractory CD19+ acute lymphoblastic leukemia patients.
Relapsed/refractory CD19 + acute lymphoblastic leukemia patients were randomly enrolled in
      this study to compare the efficacy and safety between two cohorts: 1. Humanized CD19 CAR-T
      cells； 2. Humanized CD19 CAR-T cells with CRS suppression technology.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of severe CRS
time frame: 30 days after infusion of humanized CD19 CAR-T cells
description: The safety of the humanized CD19 CAR-T cells treatment will be evaluated and the maximum tolerated dose will be determined
measure: Overall response of humanized CD19 CAR-T cells treatment who achieve morphology complete remission(CR) and MRD negativity.
time frame: 30 days after infusion of humanized CD19 CAR-T cells
description: The efficacy of the humanized CD19 CAR-T cells infusion will be estimated based on the number of participants who have morphology complete remission(CR) and MRD negativity following the humanized CD19 CAR- T cells infusion
arm group label: Experimental: Cohort 1
arm group type: Experimental
description: This cohort will determine the safety and efficacy of humanized CD19 CAR-T cells for CD19+ acute lymphoblastic leukemia
arm group label: Experimental: Cohort 2
arm group type: Experimental
description: This cohort will determine the safety and efficacy of humanized CD19 CAR-T cells with CRS suppression technology for CD19+ acute lymphoblastic leukemia.
intervention type: Biological
intervention name: Humanized CD19 CAR-T cells
description: Express a Second Generation 4-1BB:humanized CD19 CAR-T cells
arm group label: Experimental: Cohort 1
intervention type: Biological
intervention name: Humanized CD19 CAR-T cells with CRS suppression technology
description: Express a Second Generation 4-1BB:humanized CD19 CAR-T cells with CRS suppression technology
arm group label: Experimental: Cohort 2
criteria: 
gender: All
minimum age: 6 Years
maximum age: 65 Years
healthy volunteers: No
last name: Xiaowen Tang, PhD
role: Principal Investigator
affiliation: The First Affiliated Hospital of Soochow University
last name: Xiaowen Tang, PhD
phone: 8651267781525
email: tangxiaowen@suda.edu.cn
last name: Lei Yu, PhD
phone: 8613818629089
email: ylyh188@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid