<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/NCT03263208</url>
  </required_header>
  <id_info>
    <org_study_id>HenanCH152</org_study_id>
    <nct_id>NCT03263208</nct_id>
  </id_info>
  <brief_title>CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-ALL.</brief_title>
  <official_title>A Study of CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-cell Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Henan Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Pregene (ShenZhen) Biotechnology Company, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Henan Cancer Hospital</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>
      The purpose of this study is to infusion CD19 CAR-T cells to the patients with relapsed and&#xD;
      refractory CD19+ B cell leukemia, to assess the safety and feasibility of this strategy. The&#xD;
      CAR enables the T cell to recognize and kill the leukemic cell through the recognition of&#xD;
      CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+&#xD;
      leukemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Upon meeting the eligibility requirements and enrolling on study, Subjects will be collected&#xD;
      large numbers of peripheral blood mononuclear cells (PBMC) for the generation of the CD19&#xD;
      CAR-T cells. The T cells are isolated from the PBMC, transduced with a lentivirus to express&#xD;
      the CD19 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) and&#xD;
      expanded in vitro and then administered to subjects.&#xD;
&#xD;
      Subjects will have blood tests to assess safety and efficacy, and persistence of the CD19&#xD;
      CAR-T cells on week 4 after their last infusion. Following the 6 months of intensive&#xD;
      follow-up, subjects will be evaluated every 10 weeks for 1 year with a physical examination,&#xD;
      blood tests, bone marrow aspirate, MRD and persistence of CD19 CAR-T.&#xD;
&#xD;
      Some subjects will receive cetuximab for ablation of the genetically modified T cells.&#xD;
      Criteria to receive cetuximab include acute toxicities that are life threatening.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 16, 2017</start_date>
  <completion_date type="Anticipated">July 2019</completion_date>
  <primary_completion_date type="Anticipated">January 2019</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>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>safety as assessed by the occurence of study related adverse events</measure>
    <time_frame>30 days</time_frame>
    <description>number of participants with adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>anti-tumor responses of CD19 CAR-T cells</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Persistence of the CD19 CAR+ T cells</measure>
    <time_frame>1 year</time_frame>
    <description>determine duration of in vivo survival of CD19 CAR-T cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who have T cells ablated with cetuximab</measure>
    <time_frame>1 year</time_frame>
    <description>The efficacy of cetuximab to ablate the T cells will be measured by loss of detection of T cells and any associated toxicities as well as facilitating B cell recovery.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>B-cell Acute Lymphocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>CD19 CAR-T</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>patients will receive a standard pre-conditioning regime with cyclophosphamide 0.6-0.8g/m2/day IV for 2 days(Day-5 to day-4).</description>
    <arm_group_label>CD19 CAR-T</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>Fludarabine 25-30mg/m2/day IV for 3 days(Day-5 to day-3).</description>
    <arm_group_label>CD19 CAR-T</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD19 CAR-T</intervention_name>
    <description>CD19 CAR-T cells will be administered after completion of the chemotherapy.</description>
    <arm_group_label>CD19 CAR-T</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. 2 years to 70 years, expected survival &gt; 3 months;&#xD;
&#xD;
          -  2. CD19 positive B-cell acute lymphoblastic leukemia;&#xD;
&#xD;
          -  3. ECOG &lt; 2；&#xD;
&#xD;
          -  4. The tumor load in the bone marrow is less than 60%;&#xD;
&#xD;
          -  5. Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney:&#xD;
             Cr≤1.25ULN; Peripheral Blood: WBC ≥ 2.0×109/L, Hb ≥80 g/L, PLT ≥ 30×109/L）;&#xD;
&#xD;
          -  6. No leukemia cells in the central nervous system;&#xD;
&#xD;
          -  7. No serious allergic constitution;&#xD;
&#xD;
          -  8. No other serous diseases that conflicts with the clinical program;&#xD;
&#xD;
          -  9. No other cancer history;&#xD;
&#xD;
          -  10. No serious mental disorder;&#xD;
&#xD;
          -  11. female participants of reproductive potential must have a negative serum pregnancy&#xD;
             test;&#xD;
&#xD;
          -  12. Informed consent is signed by a subject or his lineal relation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Pregnant or lactating women;&#xD;
&#xD;
          -  2. Uncontrolled active infection, HIV infection, syphilis serology reaction positive;&#xD;
&#xD;
          -  3. Active hepatitis B or hepatitis C infection;&#xD;
&#xD;
          -  4. Recent or current use of glucocorticoid or other immunosuppressor;&#xD;
&#xD;
          -  5. With severe cardiac, liver, renal insufficiency, diabetes and other diseases;&#xD;
&#xD;
          -  6. Participate in other clinical research in the past three months; previously&#xD;
             treatment with any gene therapy products;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Yongping Song</last_name>
    <phone>+86 13521186987</phone>
    <email>ph200811@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Henan University of Science and Technology</name>
      <address>
        <city>Luoyang</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Haiping Yang</last_name>
      <phone>+86 13938820189</phone>
      <email>13938820189@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Henan Cancer Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yongping Song</last_name>
      <phone>+86 13521186987</phone>
      <email>ph200811@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>October 19, 2017</last_update_submitted>
  <last_update_submitted_qc>October 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2017</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>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
  </intervention_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/NCT03263208
org study id: HenanCH152
nct id: NCT03263208
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to infusion CD19 CAR-T cells to the patients with relapsed and
      refractory CD19+ B cell leukemia, to assess the safety and feasibility of this strategy. The
      CAR enables the T cell to recognize and kill the leukemic cell through the recognition of
      CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+
      leukemia.
Upon meeting the eligibility requirements and enrolling on study, Subjects will be collected
      large numbers of peripheral blood mononuclear cells (PBMC) for the generation of the CD19
      CAR-T cells. The T cells are isolated from the PBMC, transduced with a lentivirus to express
      the CD19 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) and
      expanded in vitro and then administered to subjects.

      Subjects will have blood tests to assess safety and efficacy, and persistence of the CD19
      CAR-T cells on week 4 after their last infusion. Following the 6 months of intensive
      follow-up, subjects will be evaluated every 10 weeks for 1 year with a physical examination,
      blood tests, bone marrow aspirate, MRD and persistence of CD19 CAR-T.

      Some subjects will receive cetuximab for ablation of the genetically modified T cells.
      Criteria to receive cetuximab include acute toxicities that are life threatening.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: safety as assessed by the occurence of study related adverse events
time frame: 30 days
description: number of participants with adverse events
measure: anti-tumor responses of CD19 CAR-T cells
time frame: 1 year
measure: Persistence of the CD19 CAR+ T cells
time frame: 1 year
description: determine duration of in vivo survival of CD19 CAR-T cells
measure: Number of participants who have T cells ablated with cetuximab
time frame: 1 year
description: The efficacy of cetuximab to ablate the T cells will be measured by loss of detection of T cells and any associated toxicities as well as facilitating B cell recovery.
arm group label: CD19 CAR-T
arm group type: Experimental
description: A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
intervention type: Drug
intervention name: Cyclophosphamide
description: patients will receive a standard pre-conditioning regime with cyclophosphamide 0.6-0.8g/m2/day IV for 2 days(Day-5 to day-4).
arm group label: CD19 CAR-T
intervention type: Drug
intervention name: Fludarabine
description: Fludarabine 25-30mg/m2/day IV for 3 days(Day-5 to day-3).
arm group label: CD19 CAR-T
intervention type: Biological
intervention name: CD19 CAR-T
description: CD19 CAR-T cells will be administered after completion of the chemotherapy.
arm group label: CD19 CAR-T
criteria: 
gender: All
minimum age: 2 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yongping Song
phone: +86 13521186987
email: ph200811@163.com
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Cyclophosphamide
mesh term: Fludarabine