<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/NCT02992834</url>
  </required_header>
  <id_info>
    <org_study_id>CAAA</org_study_id>
    <nct_id>NCT02992834</nct_id>
  </id_info>
  <brief_title>Anti-CD19:TCRζ Chimeric Antigen Receptor-T Cells in the Treatment for CD19+ B Cell Lymphoma</brief_title>
  <official_title>Anti-CD19:TCRζ Chimeric Antigen Receptor-T Cells in the Treatment for Chemotherapy-resistant or Refractory CD19+B Cell Lymphoma:a Double-arm, Single Center, Open-label Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>jiangjingting</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The First People's Hospital of Changzhou</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric&#xD;
      Antigen Receptor (CAR) redirected allogeneic T-cells in patients with chemotherapy-resistant&#xD;
      or refractory CD19+ B cell lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-centre, randomised, open label Phase I clinical trial of CD19 Chimeric&#xD;
      Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in patients with chemotherapy-resistant or&#xD;
      refractory CD19+ B cell lymphoma. Following informed consent and registration to the trial,&#xD;
      Patients will receive the allogeneic CD19 CAR T-cells following lymphodepleting chemotherapy.&#xD;
      The study will evaluate the safety, efficacy and duration of response of the CD19 CAR T-cells&#xD;
      in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">January 2022</completion_date>
  <primary_completion_date type="Anticipated">August 2020</primary_completion_date>
  <phase>Phase 4</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>overall survival</measure>
    <time_frame>5 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>progression-free survival</measure>
    <time_frame>56 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>56 day</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Lymphoma, B Cell</condition>
  <arm_group>
    <arm_group_label>IL-2 pre-treated CD19 cells</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Initial therapy: IL-2 (interleukin,IL)stimulated, CD28-ζ-vector (cluster of differentiation 28,CD28)transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IL-7/IL-15 pre-treated CD19 cells</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Initial therapy: IL-7/IL-15 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IL-2 pre-treated CD19 cells</intervention_name>
    <description>IL-2 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion</description>
    <arm_group_label>IL-2 pre-treated CD19 cells</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IL-7/IL-15 pre-treated CD19 cells</intervention_name>
    <description>IL-7/IL-15 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion</description>
    <arm_group_label>IL-7/IL-15 pre-treated CD19 cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Enrollment for enough male or female patients with CD19+ hematological malignancies,&#xD;
        without regimens for cure (autologous or allogeneic stem cell transplantation), and having&#xD;
        a poor prognosis (several months to 2 years) under current optional regimens&#xD;
&#xD;
          1. Age ranges from 18 to 70 years old&#xD;
&#xD;
          2. Expected survival time longer than 12 weeks&#xD;
&#xD;
          3. Performance status score 0-2&#xD;
&#xD;
          4. Pathologically confirmed CD19+ lymphoma (CD19+ follicular lymphoma, Mantle cell&#xD;
             lymphoma, diffuse large B cell lymphoma) and meets at least one of follows:&#xD;
&#xD;
               1. having received at least 2-4 cycles of combined chemotherapy (excluding&#xD;
                  monoclonal antibody monotherapy, such as rituximab) but do not reach a complete&#xD;
                  response; recurrent disease; not applicable for conventional stem cell&#xD;
                  transplantation; being partial responsible or stable but not complete responsible&#xD;
                  after the latest therapy&#xD;
&#xD;
               2. recurrence develops after stem cell transplantation&#xD;
&#xD;
               3. diagnosis confirmed but refusing to receive conventional therapy&#xD;
&#xD;
          5. Creatinine&lt;2.5 mg/dl；&#xD;
&#xD;
          6. alanine aminotransferase/aspartate aminotransferase lower than 3 folds of normal range&#xD;
&#xD;
          7. Bilirubin&lt;2.0 mg/dl；&#xD;
&#xD;
          8. Venous channel available and no contraindications for leukocyte collection&#xD;
&#xD;
          9. Reliable contraception from the beginning to 30 days after discontinuation of therapy&#xD;
&#xD;
         10. Informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Central nerve system invasion with symptoms&#xD;
&#xD;
          2. Other concurrent uncontrolled malignancies&#xD;
&#xD;
          3. Hepatitis B infection or active period of hepatitis C, HIV infection&#xD;
&#xD;
          4. Other uncontrolled diseases hampering the intervention in the study&#xD;
&#xD;
          5. Coronary heart disease, angina, myocardial infarction, arrhythmia, cerebral&#xD;
             thrombosis, cerebral hemorrhage and other serious cardiovascular or cerebrovascular&#xD;
             diseases.&#xD;
&#xD;
          6. Grade 2-3 or uncontrolled hypertension&#xD;
&#xD;
          7. History of uncontrolled mental disease&#xD;
&#xD;
          8. Not suitable for participation judged by researchers&#xD;
&#xD;
          9. Immunosuppressive agents administered due to organ transplantation, not including&#xD;
             recent or current inhaled corticosteroid&#xD;
&#xD;
         10. Medical history of mental diseases or abnormities of lab tests might increase the&#xD;
             risks of participation in study or drug administration, or interfering the results&#xD;
&#xD;
         11. Screening suggesting transfection efficiency of targeting cells lower than 30% or cell&#xD;
             expansion deficiency under CD3/CD28 (cluster of differentiation 3,CD3)stimulation&#xD;
             (less than 5 folds)&#xD;
&#xD;
         12. Unstable pulmonary embolism, deep venous thromboembolism or other major&#xD;
             arterial/venous thromboembolism events develop in 30 days before the randomization. If&#xD;
             anti-coagulation therapy is received, the treatment dose should reach stability before&#xD;
             the randomization.&#xD;
&#xD;
         13. Pregnancy or lactation, or pregnancy planned during the study or in 2 months after the&#xD;
             study&#xD;
&#xD;
         14. Reliable contraception not accepted during the study or in 2 months after the study.&#xD;
             Female subjects are required to provide negative results from serum or urine pregnancy&#xD;
             test 48 hours before therapy&#xD;
&#xD;
         15. Systematic active or uncontrolled infection (excluding infection of urinary tract or&#xD;
             upper respiratory tract infection) in 14 days before the randomization&#xD;
&#xD;
         16. Informed consent not signed or study rules violated&#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>Jingting Jiang, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First People's Hospital of Changzhou</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jingting Jiang, Professor</last_name>
    <email>jjtnew@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>First People's Hospital of Changzhou</name>
      <address>
        <city>Changzhou</city>
        <state>Jiangsu</state>
        <zip>213003</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Qi Zhou, Doctor</last_name>
      <email>dr_qzhou@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Rafiq S, Purdon TJ, Daniyan AF, Koneru M, Dao T, Liu C, Scheinberg DA, Brentjens RJ. Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen. Leukemia. 2017 Aug;31(8):1788-1797. doi: 10.1038/leu.2016.373. Epub 2016 Dec 7.</citation>
    <PMID>27924074</PMID>
  </reference>
  <reference>
    <citation>Minagawa K, Jamil MO, Al-Obaidi M, Pereboeva L, Salzman D, Erba HP, Lamb LS, Bhatia R, Mineishi S, Di Stasi A. In Vitro Pre-Clinical Validation of Suicide Gene Modified Anti-CD33 Redirected Chimeric Antigen Receptor T-Cells for Acute Myeloid Leukemia. PLoS One. 2016 Dec 1;11(12):e0166891. doi: 10.1371/journal.pone.0166891. eCollection 2016. Erratum In: PLoS One. 2017 Feb 15;12 (2):e0172640.</citation>
    <PMID>27907031</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 12, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>December 12, 2016</last_update_submitted>
  <last_update_submitted_qc>December 12, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>The First People's Hospital of Changzhou</investigator_affiliation>
    <investigator_full_name>jiangjingting</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02992834
org study id: CAAA
nct id: NCT02992834
lead sponsor: 
has dmc: Yes
This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric
      Antigen Receptor (CAR) redirected allogeneic T-cells in patients with chemotherapy-resistant
      or refractory CD19+ B cell lymphoma.
This is a single-centre, randomised, open label Phase I clinical trial of CD19 Chimeric
      Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in patients with chemotherapy-resistant or
      refractory CD19+ B cell lymphoma. Following informed consent and registration to the trial,
      Patients will receive the allogeneic CD19 CAR T-cells following lymphodepleting chemotherapy.
      The study will evaluate the safety, efficacy and duration of response of the CD19 CAR T-cells
      in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: overall survival
time frame: 5 year
measure: progression-free survival
time frame: 56 day
measure: Objective Response Rate
time frame: 56 day
arm group label: IL-2 pre-treated CD19 cells
arm group type: Active Comparator
description: Initial therapy: IL-2 (interleukin,IL)stimulated, CD28-ζ-vector (cluster of differentiation 28,CD28)transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion
arm group label: IL-7/IL-15 pre-treated CD19 cells
arm group type: Active Comparator
description: Initial therapy: IL-7/IL-15 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion
intervention type: Biological
intervention name: IL-2 pre-treated CD19 cells
description: IL-2 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion
arm group label: IL-2 pre-treated CD19 cells
intervention type: Biological
intervention name: IL-7/IL-15 pre-treated CD19 cells
description: IL-7/IL-15 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion
arm group label: IL-7/IL-15 pre-treated CD19 cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jingting Jiang, Professor
role: Principal Investigator
affiliation: The First People's Hospital of Changzhou
last name: Jingting Jiang, Professor
email: jjtnew@163.com
facility: 
contact: 
country: China
citation: Rafiq S, Purdon TJ, Daniyan AF, Koneru M, Dao T, Liu C, Scheinberg DA, Brentjens RJ. Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen. Leukemia. 2017 Aug;31(8):1788-1797. doi: 10.1038/leu.2016.373. Epub 2016 Dec 7.
PMID: 27924074
citation: Minagawa K, Jamil MO, Al-Obaidi M, Pereboeva L, Salzman D, Erba HP, Lamb LS, Bhatia R, Mineishi S, Di Stasi A. In Vitro Pre-Clinical Validation of Suicide Gene Modified Anti-CD33 Redirected Chimeric Antigen Receptor T-Cells for Acute Myeloid Leukemia. PLoS One. 2016 Dec 1;11(12):e0166891. doi: 10.1371/journal.pone.0166891. eCollection 2016. Erratum In: PLoS One. 2017 Feb 15;12 (2):e0172640.
PMID: 27907031
responsible party type: Sponsor-Investigator
investigator affiliation: The First People's Hospital of Changzhou
investigator full name: jiangjingting
investigator title: Professor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
sharing ipd: No