<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/NCT03030976</url>
  </required_header>
  <id_info>
    <org_study_id>CD19-CART for SLE</org_study_id>
    <nct_id>NCT03030976</nct_id>
  </id_info>
  <brief_title>A Study of CD19 Redirected Autologous T Cells for CD19 Positive Systemic Lupus Erythematosus (SLE)</brief_title>
  <official_title>An Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With CD19+ B Cell Systemic Lupus Erythematosus (SLE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai GeneChem Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>RenJi Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai GeneChem Co., Ltd.</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>
      CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has&#xD;
      been hailed for its promising remission rates after early stage clinical trials for acute&#xD;
      lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases.&#xD;
      Researchers only use it for the treatment of multiple sclerosis (MS, an autoimmune disease of&#xD;
      the central nervous system). SLE is a kind of autoimmune diseases which involving multiple&#xD;
      systems, organs and with the present of a variety of autoantibodies. In the conventional&#xD;
      treatment options, SLE could be treated with chemotherapy drugs or hormone drugs. But&#xD;
      chemotherapy and hormone drugs could barely cured SLE. And now, chimeric antigen receptor&#xD;
      modified T cell infusion maybe an effective treatment to solve these problems. The&#xD;
      investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat&#xD;
      patients with SLE. The purpose of this study is to assess the safety and efficacy of this 2nd&#xD;
      CAR-T cells in the treatment of SLE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating&#xD;
      patients with systemic lupus erythematosus（SLE）.The investigators constructed a 2nd CAR,&#xD;
      using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by&#xD;
      a suitable hinge and transmembrane domain sequences. The infusion dose is (1-10)E6 CAR&#xD;
      positive T cells/kg, and the specific cells numbers depends on the situation of individual&#xD;
      CAR-T cells preparation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">March 2017</start_date>
  <completion_date type="Anticipated">March 2018</completion_date>
  <primary_completion_date type="Anticipated">January 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</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 of CAR-T cell（i.v.）by number of patients with adverse event</measure>
    <time_frame>6 weeks</time_frame>
    <description>adverse event is evaluated with CTCAE, version 4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with tumor response</measure>
    <time_frame>8 weeks</time_frame>
    <description>summarize tumor response by overall response rates</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3. Detection of transferred T cells in the circulation using quantitative -PCR</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">5</enrollment>
  <condition>Systemic Lupus Erythematosus (SLE)</condition>
  <arm_group>
    <arm_group_label>Reduce B cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive cyclophosphamide to reduce B cells before CD19-CART infusion. It will also reduce the side effects of cell damage due to antitumor activity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment of SLE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive anti-CD19-CAR-T cells to treatment of SLE. The purpose of this study is to assess the safety and efficacy of CD19 CAR-T cells in the treatment of SLE.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cyclophosphamide</intervention_name>
    <description>Patients receive cyclophosphamide (Cy) on day -2 and day -1 to reduce B cells. The dose is 0.5g/m2/d.</description>
    <arm_group_label>Reduce B cells</arm_group_label>
    <other_name>Cy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>anti-CD19-CAR-T cells</intervention_name>
    <description>A 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge &amp; transmembrane domain sequences. Patients infused with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity to treatment of SLE. The dose is 1E6~1E7 CD19-CAR positive T cells. The cells infusion process may last for 30 min.</description>
    <arm_group_label>Treatment of SLE</arm_group_label>
    <other_name>2nd CAR-T</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of systemic lupus erythematosus (SLE) patients&#xD;
&#xD;
          -  Patients with CD19+ B-cell SLE as confirmed by Flow Cytometry&#xD;
&#xD;
          -  Age: 18-69 years old&#xD;
&#xD;
          -  Creatinine &lt; 1.5 mg/dl&#xD;
&#xD;
          -  cardiac ejection fraction&gt;55%&#xD;
&#xD;
          -  hemoglobin&gt;9g/dL&#xD;
&#xD;
          -  Bilirubin &lt;2.0 mg/dl&#xD;
&#xD;
          -  Successful test expansion of T-cells&#xD;
&#xD;
          -  Adequate venous access for apheresis, and no other contraindications for leukapheresis&#xD;
&#xD;
          -  Voluntary informed consent is given&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Uncontrolled active infection&#xD;
&#xD;
          -  Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not&#xD;
             exclusionary&#xD;
&#xD;
          -  Previously treatment with any gene therapy products&#xD;
&#xD;
          -  Feasibility assessment during screening demonstrates&lt;5% transduction of target&#xD;
             lymphocytes, or insufficient expansion (&lt;5-fold) in response to CD3/CD28 costimulation&#xD;
&#xD;
          -  Any serious, uncontrolled diseases (including, but not limit to, unstable angina&#xD;
             pectoris, congestive heart failure, serious arrhythmia)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qiang Guo, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>RenJi Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Qiang Guo, Doctor</last_name>
    <phone>86-21-63835620</phone>
    <email>bluedescent@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xuejun Yu, Master</last_name>
    <phone>86-21-51320189</phone>
    <phone_ext>8306</phone_ext>
    <email>yuxuejun@genechem.com.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai Jiaotong University School of Medicine, Renji Hospital</name>
      <address>
        <city>Shanghai</city>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Qiang Guo, Doctor</last_name>
      <phone>86-21-63835620</phone>
      <email>bluedescent@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 22, 2017</study_first_submitted>
  <study_first_submitted_qc>January 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>February 4, 2017</last_update_submitted>
  <last_update_submitted_qc>February 4, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CD19</keyword>
  <keyword>CAR-T</keyword>
  <keyword>SLE</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lupus Erythematosus, Systemic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03030976
org study id: CD19-CART for SLE
nct id: NCT03030976
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has
      been hailed for its promising remission rates after early stage clinical trials for acute
      lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases.
      Researchers only use it for the treatment of multiple sclerosis (MS, an autoimmune disease of
      the central nervous system). SLE is a kind of autoimmune diseases which involving multiple
      systems, organs and with the present of a variety of autoantibodies. In the conventional
      treatment options, SLE could be treated with chemotherapy drugs or hormone drugs. But
      chemotherapy and hormone drugs could barely cured SLE. And now, chimeric antigen receptor
      modified T cell infusion maybe an effective treatment to solve these problems. The
      investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat
      patients with SLE. The purpose of this study is to assess the safety and efficacy of this 2nd
      CAR-T cells in the treatment of SLE.
This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating
      patients with systemic lupus erythematosus（SLE）.The investigators constructed a 2nd CAR,
      using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by
      a suitable hinge and transmembrane domain sequences. The infusion dose is (1-10)E6 CAR
      positive T cells/kg, and the specific cells numbers depends on the situation of individual
      CAR-T cells preparation.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of CAR-T cell（i.v.）by number of patients with adverse event
time frame: 6 weeks
description: adverse event is evaluated with CTCAE, version 4.0
measure: Number of patients with tumor response
time frame: 8 weeks
description: summarize tumor response by overall response rates
measure: 3. Detection of transferred T cells in the circulation using quantitative -PCR
time frame: 6 weeks
arm group label: Reduce B cells
arm group type: Experimental
description: Patients receive cyclophosphamide to reduce B cells before CD19-CART infusion. It will also reduce the side effects of cell damage due to antitumor activity.
arm group label: Treatment of SLE
arm group type: Experimental
description: Patients receive anti-CD19-CAR-T cells to treatment of SLE. The purpose of this study is to assess the safety and efficacy of CD19 CAR-T cells in the treatment of SLE.
intervention type: Drug
intervention name: cyclophosphamide
description: Patients receive cyclophosphamide (Cy) on day -2 and day -1 to reduce B cells. The dose is 0.5g/m2/d.
arm group label: Reduce B cells
other name: Cy
intervention type: Drug
intervention name: anti-CD19-CAR-T cells
description: A 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge & transmembrane domain sequences. Patients infused with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity to treatment of SLE. The dose is 1E6~1E7 CD19-CAR positive T cells. The cells infusion process may last for 30 min.
arm group label: Treatment of SLE
other name: 2nd CAR-T
criteria: 
gender: All
minimum age: 18 Years
maximum age: 69 Years
healthy volunteers: No
last name: Qiang Guo, Doctor
role: Principal Investigator
affiliation: RenJi Hospital
last name: Qiang Guo, Doctor
phone: 86-21-63835620
email: bluedescent@126.com
last name: Xuejun Yu, Master
phone: 86-21-51320189
phone ext: 8306
email: yuxuejun@genechem.com.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic
mesh term: Cyclophosphamide
sharing ipd: Undecided