<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/NCT02975687</url>
  </required_header>
  <id_info>
    <org_study_id>XH-CD19CART-001</org_study_id>
    <secondary_id>HY001001</secondary_id>
    <nct_id>NCT02975687</nct_id>
  </id_info>
  <brief_title>CD19 CAR T Cells in Patients With Resistant or Refractory CD19+ Acute Lymphoblastic Leukemia</brief_title>
  <official_title>CD19 CAR T Cells in Patients With Resistant or Refractory CD19+ Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Hematology &amp; Blood Diseases Hospital, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Union Stem cell &amp; gene engineering Co.LTD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Juventas Cell Therapy Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Hematology &amp; Blood Diseases Hospital, China</source>
  <brief_summary>
    <textblock>
      In this single-center, open-label, no control, prospective clinical trial, a total of 20&#xD;
      resistant or refractory CD19+ B cell acute lymphoblastic leukemia (ALL) patients will be&#xD;
      enrolled. CD19 CAR T cells will be administered by i.v. injection as a using a &quot;split dose&quot;&#xD;
      (total dose of 5x10^6/kg-5x10^7/kg) approach to dosing:10% on day 0, 30% on day 1 and 60% on&#xD;
      day 2. The purpose of current study is to determine the clinical efficacy and safety of CD19&#xD;
      CAR T cells in patients with chemotherapy resistant or refractory CD19+ ALL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this single-center, open-label, nonrandomized, no control, prospective clinical trial, a&#xD;
      total of 20 resistant or refractory CD19+ B cell acute lymphoblastic leukemia (ALL) patients&#xD;
      will be enrolled. Patients will be diagnosed according to morphologic, immunologic,&#xD;
      cytogenetic and molecular(MICM) criteria, including bone marrow morphology, immunophenotype,&#xD;
      cytogenetic and molecular examination. CD19 CAR T cells transduced with a lentiviral vector&#xD;
      to express anti-CD19 scFv TCRζ:4-1BB,administered by i.v. injection as a using a &quot;split dose&quot;&#xD;
      (total dose of 5x10^6/kg-5x10^7/kg) approach to dosing:10% on day 0, 30% on day 1 and 60% on&#xD;
      day 2. This protocol will be given to subjects with unmet medical needs for which there are&#xD;
      no effective therapies known at this time. Side effects of CD19 CAR T cells therapy will be&#xD;
      monitored. The purpose of current study is to determine the clinical efficacy and safety of&#xD;
      CD19 CAR T cells therapy in patients with chemotherapy resistant or refractory CD19+ ALL.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 2018</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>The complete remission (CR) rate</measure>
    <time_frame>Participants will be followed for the duration of the treatment, an expected average of 12 months.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival (DFS)</measure>
    <time_frame>From the date of complete remission(CR) until the date of documented relapse,assessed up to 60 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse event of CD19 CAR T cells treatment</measure>
    <time_frame>Participants will be followed for the duration of the treatment, an expected average of 24 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grade of adverse event of CD19 CAR T cells treatment</measure>
    <time_frame>Participants will be followed for the duration of the treatment, an expected average of 24 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of in vivo survival of CD19 CAR T cells.</measure>
    <time_frame>Participants will be followed for the duration of the treatment, an expected average of 24 months.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Acute Lymphoblastic Leukemia, Adult B-Cell</condition>
  <condition>Acute Lymphoblastic Leukaemia Recurrent</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CD19 CAR T cells will be administered by i.v. injection as a using a &quot;split dose&quot; (total dose of 5x10^6/kg-5x10^7/kg) approach to dosing:10% on day 0, 30% on day 1 and 60% on day 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD19 CAR T cells</intervention_name>
    <description>CD19 CAR T cells was transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB.</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 18 to 70 years with relapsed or refractory CD19 positive ALL(ie, ≥20%&#xD;
             blasts CD19-positive) due to receive either salvage 1 or salvage 2 therapy. Ph+ ALL&#xD;
             patients must have failed treatment with at least 1 second generation tyrosine kinase&#xD;
             inhibitor.&#xD;
&#xD;
          -  Bone marrow involvement with≥20% lymphoblasts.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.&#xD;
&#xD;
          -  Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of&#xD;
             normal（ULN）; serum glutamic-oxaloacetic transaminase(SGOT) and serum glutamic pyruvic&#xD;
             transaminase(SGPT) ≤ 2.5 x ULN; Creatinine ≤ 1.5 x ULN or any serum creatinine level&#xD;
             associated with a measured or calculated creatinine clearance of ≥ 40ml/min.&#xD;
&#xD;
          -  Patients should sign informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Isolated extramedullary relapse.&#xD;
&#xD;
          -  Active central nervous system leukemia.&#xD;
&#xD;
          -  Prior chemotherapy within ≤2 weeks before enrollment with the following exceptions:&#xD;
             steroids, hydroxyurea, oral mercaptopurine, methotrexate, vincristine, thioguanine,&#xD;
             and tyrosine kinase inhibitors are permitted within 2 weeks of enrollment as&#xD;
             maintenance or to reduce the peripheral blood blast count. Patients must have&#xD;
             recovered from acute toxicity of all previous therapy prior to enrollment.&#xD;
&#xD;
          -  Prior allogeneic hematopoietic stem cell transplant (HSCT) ≤ 4 months before&#xD;
             enrollment. Patients must have completed immunosuppression therapy prior to&#xD;
             enrollment. At enrollment, patients must not have &gt; grade 2 acute GVHD, or either&#xD;
             moderate or severe limited chronic GVHD, or extensive GVHD of any severity.&#xD;
&#xD;
          -  Peripheral lymphoblasts &gt; 10,000/μl (treatment with hydroxyurea and/or steroids is&#xD;
             permitted within 2 weeks of enrollment to reduce the WBC count).&#xD;
&#xD;
          -  Known systemic vasculitides, primary or secondary immunodeficiency(such as HIV&#xD;
             infection or severe inflammatory disease).&#xD;
&#xD;
          -  Major surgery within ≤ 4 weeks before enrollment.&#xD;
&#xD;
          -  Impaired cardiac function:Ejection fraction &lt; 45 % on MUGA scan. QTc interval &gt; 450&#xD;
             msec on baseline ECG (using the QTcB formula). If QTcB interval&gt;450 msec and&#xD;
             electrolytes are not within normal ranges, electrolytes should be corrected and then&#xD;
             the patient re-screened for QTc. Myocardial infarction within 6 months prior to&#xD;
             starting study; other clinically significant heart disease (e.g. unstable angina,&#xD;
             congestive heart failure or uncontrolled hypertension, uncontrolled arrhythmias).&#xD;
&#xD;
          -  Administration of live vaccine ≤ 4 weeks before enrollment.&#xD;
&#xD;
          -  Other concurrent severe and/or uncontrolled medical conditions:&#xD;
&#xD;
        Patients with another primary malignant disease, except those that do not currently require&#xD;
        treatment; acute or chronic liver, pancreatic or severe renal disease; another severe&#xD;
        and/or life-threatening medical disease.&#xD;
&#xD;
          -  Evidence of uncontrolled current serious active infection.&#xD;
&#xD;
          -  Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential&#xD;
             without a negative pregnancy test prior to baseline and (d) male or female of&#xD;
             childbearing potential unwilling to use contraceptive precautions throughout the trial&#xD;
             (post-menopausal women must be amenorrheic for at least 12 months to be considered of&#xD;
             non-childbearing potential).&#xD;
&#xD;
          -  Who is known human deficiency virus (HIV) positive.&#xD;
&#xD;
          -  Use of any other investigational agent in the last 30 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianxiang Wang, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of Hematology &amp; Blood Diseases Hospital</name>
      <address>
        <city>Tianjin</city>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>July 7, 2019</last_update_submitted>
  <last_update_submitted_qc>July 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</investigator_affiliation>
    <investigator_full_name>wang, jianxiang</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <keyword>Acute</keyword>
  <keyword>Leukemia</keyword>
  <keyword>Lymphoid</keyword>
  <keyword>CD19</keyword>
  <keyword>Refractory</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/NCT02975687
org study id: XH-CD19CART-001
secondary id: HY001001
nct id: NCT02975687
lead sponsor: 
collaborator: 
collaborator: 
In this single-center, open-label, no control, prospective clinical trial, a total of 20
      resistant or refractory CD19+ B cell acute lymphoblastic leukemia (ALL) patients will be
      enrolled. CD19 CAR T cells will be administered by i.v. injection as a using a "split dose"
      (total dose of 5x10^6/kg-5x10^7/kg) approach to dosing:10% on day 0, 30% on day 1 and 60% on
      day 2. The purpose of current study is to determine the clinical efficacy and safety of CD19
      CAR T cells in patients with chemotherapy resistant or refractory CD19+ ALL.
In this single-center, open-label, nonrandomized, no control, prospective clinical trial, a
      total of 20 resistant or refractory CD19+ B cell acute lymphoblastic leukemia (ALL) patients
      will be enrolled. Patients will be diagnosed according to morphologic, immunologic,
      cytogenetic and molecular(MICM) criteria, including bone marrow morphology, immunophenotype,
      cytogenetic and molecular examination. CD19 CAR T cells transduced with a lentiviral vector
      to express anti-CD19 scFv TCRζ:4-1BB,administered by i.v. injection as a using a "split dose"
      (total dose of 5x10^6/kg-5x10^7/kg) approach to dosing:10% on day 0, 30% on day 1 and 60% on
      day 2. This protocol will be given to subjects with unmet medical needs for which there are
      no effective therapies known at this time. Side effects of CD19 CAR T cells therapy will be
      monitored. The purpose of current study is to determine the clinical efficacy and safety of
      CD19 CAR T cells therapy in patients with chemotherapy resistant or refractory CD19+ ALL.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The complete remission (CR) rate
time frame: Participants will be followed for the duration of the treatment, an expected average of 12 months.
measure: Disease-free survival (DFS)
time frame: From the date of complete remission(CR) until the date of documented relapse,assessed up to 60 months.
measure: Number of adverse event of CD19 CAR T cells treatment
time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
measure: Grade of adverse event of CD19 CAR T cells treatment
time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
measure: Duration of in vivo survival of CD19 CAR T cells.
time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
arm group label: Arm A
arm group type: Experimental
description: CD19 CAR T cells will be administered by i.v. injection as a using a "split dose" (total dose of 5x10^6/kg-5x10^7/kg) approach to dosing:10% on day 0, 30% on day 1 and 60% on day 2.
intervention type: Biological
intervention name: CD19 CAR T cells
description: CD19 CAR T cells was transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB.
arm group label: Arm A
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jianxiang Wang, Dr.
role: Principal Investigator
affiliation: Institute of Hematology & Blood Diseases Hospital, China
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Institute of Hematology & Blood Diseases Hospital, China
investigator full name: wang, jianxiang
investigator title: Dr.
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid