<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/NCT02247609</url>
  </required_header>
  <id_info>
    <org_study_id>19273-4SCAR</org_study_id>
    <nct_id>NCT02247609</nct_id>
  </id_info>
  <brief_title>Evaluation of 4th Generation Safety-designed CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas</brief_title>
  <acronym>4SCAR19273</acronym>
  <official_title>Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently, a majority of B cell lymphomas cannot be cured by standard chemo-radiotherapy.&#xD;
      Most B cell lymphomas express cluster of differentiation antigen 19 (CD19), which represents&#xD;
      a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. This&#xD;
      study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal&#xD;
      mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CD19 single chain antibody-based chimeric antigen receptor (CAR)-engineered T cells have&#xD;
      demonstrated great clinical potential in treating chronic and acute B cell leukemias. B cell&#xD;
      lymphomas, similar to B cell leukemias, express CD19 surface molecules, and the majority of&#xD;
      the B cell lymphoma patients cannot be cured by standard chemo-radiotherapy. CD19 CAR-based&#xD;
      adoptive T cell therapy is associated with an unwanted adverse effect, the loss of CD19 B&#xD;
      cells, which results in humoral immune deficiency. This study will evaluate a novel 4th&#xD;
      generation CD19 CAR engineered with a self-withdrawal genetic mechanism (19273-4SCAR) for&#xD;
      both efficacy and safety in lymphoma patients. The 4th generation design of the CAR&#xD;
      incorporates the intracellular signaling domain of cluster of differentiation antigen 27&#xD;
      (CD27), known to be associated with T cell activation, survival and longevity. The inducible&#xD;
      caspase 9 self-withdrawal design allows for rapid elimination of the infused CAR T cells upon&#xD;
      complete eradication of the tumor cells, which will be followed by the recovery of humoral&#xD;
      immunity. Patients receiving the 19273-4SCAR T cells will be closely monitored for infusion&#xD;
      response, tumor eradication effect, longevity of the CAR T cells, and the recovery of B cell&#xD;
      functions after withdrawal of the CAR T cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2014</start_date>
  <completion_date type="Anticipated">October 2017</completion_date>
  <primary_completion_date type="Anticipated">October 2016</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>Number of patients with adverse events.</measure>
    <time_frame>2 years.</time_frame>
    <description>Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival time of Anti-CD19 CAR T cells in vivo.</measure>
    <time_frame>2 years.</time_frame>
    <description>Measure the survival of 4th generation CAR T cells transduced with the anti-CD19 lentiviral vector.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rates to the 4th generation CAR T cells.</measure>
    <time_frame>2 years.</time_frame>
    <description>Describe the response rates of patients treated with 4th generation CAR T cells, including partial remission (PR), complete remission (CR), stable disease (SD) and progressive disease (PD).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival time of the patients.</measure>
    <time_frame>2 years.</time_frame>
    <description>Evaluate the survival time of the patients treated with the 4th generation CAR T cells, including progression free survival (PFS) and overall survival (OS).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>B-cell Lymphomas</condition>
  <arm_group>
    <arm_group_label>CAR T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous 4th generation anti-CD19-CAR T cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Anti-CD19 CAR T cells</intervention_name>
    <description>Autologous 4th generation withdrawable lentiviral-transduced anti-CD19-CAR T cells</description>
    <arm_group_label>CAR T cells</arm_group_label>
    <other_name>19273-4SCAR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Relapsed or refractory CD19(+) B cell lymphoma patients proved by&#xD;
             immuno-histochemistry (IHC) or Flow-cytometry.&#xD;
&#xD;
          -  Not eligible for autologous stem-cell transplantation (ASCT) or relapsed after ASCT.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.&#xD;
&#xD;
          -  Age≥18.&#xD;
&#xD;
          -  Pulse oximetry of &gt; 90% on room air.&#xD;
&#xD;
          -  Adequate hepatic function, defined as alanine transaminase (ALT) &lt;3 x upper limit of&#xD;
             normal (ULN), aspartate aminotransferase (AST) &lt;3 x ULN; serum bilirubin and alkaline&#xD;
             phosphatase &lt;2 x ULN.&#xD;
&#xD;
          -  Adequate renal function, defined as serum creatinine &lt;2.0mg/dl.&#xD;
&#xD;
          -  Adequate heart function with LVEF≥50%&#xD;
&#xD;
          -  Hb≥80g/L&#xD;
&#xD;
          -  Measurable disease can be identified.&#xD;
&#xD;
          -  Life expectancy ≥3 months.&#xD;
&#xD;
          -  Sexually active patients must be willing to utilize one of the more effective birth&#xD;
             control methods during the study and for 1 year after the study is concluded. The male&#xD;
             partner should use a condom.&#xD;
&#xD;
          -  Patients must sign an informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled active infection.&#xD;
&#xD;
          -  Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV).&#xD;
&#xD;
          -  HIV positive&#xD;
&#xD;
          -  Pregnant or lactating.&#xD;
&#xD;
          -  Currently enrolled in another clinical trial.&#xD;
&#xD;
          -  Concurrent use of systemic steroids.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jun Zhu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jun Zhu, MD</last_name>
    <phone>+86-10-88196596</phone>
    <email>zj@bjcancer.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Peking University Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jun Zhu, MD</last_name>
      <phone>+86-10-88196596</phone>
      <email>zj@bjcancer.org</email>
    </contact>
    <investigator>
      <last_name>Jun Zhu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>October 16, 2014</last_update_submitted>
  <last_update_submitted_qc>October 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 20, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University</investigator_affiliation>
    <investigator_full_name>Jun Zhu</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>B cell lymphoma</keyword>
  <keyword>non-Hodgkin's lymphoma</keyword>
  <keyword>Burkitt lymphoma</keyword>
  <keyword>diffused large B cell lymphoma</keyword>
  <keyword>B cell malignancy</keyword>
  <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>
  <!-- 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/NCT02247609
org study id: 19273-4SCAR
nct id: NCT02247609
lead sponsor: 
collaborator: 
has dmc: Yes
Currently, a majority of B cell lymphomas cannot be cured by standard chemo-radiotherapy.
      Most B cell lymphomas express cluster of differentiation antigen 19 (CD19), which represents
      a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. This
      study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal
      mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients.
CD19 single chain antibody-based chimeric antigen receptor (CAR)-engineered T cells have
      demonstrated great clinical potential in treating chronic and acute B cell leukemias. B cell
      lymphomas, similar to B cell leukemias, express CD19 surface molecules, and the majority of
      the B cell lymphoma patients cannot be cured by standard chemo-radiotherapy. CD19 CAR-based
      adoptive T cell therapy is associated with an unwanted adverse effect, the loss of CD19 B
      cells, which results in humoral immune deficiency. This study will evaluate a novel 4th
      generation CD19 CAR engineered with a self-withdrawal genetic mechanism (19273-4SCAR) for
      both efficacy and safety in lymphoma patients. The 4th generation design of the CAR
      incorporates the intracellular signaling domain of cluster of differentiation antigen 27
      (CD27), known to be associated with T cell activation, survival and longevity. The inducible
      caspase 9 self-withdrawal design allows for rapid elimination of the infused CAR T cells upon
      complete eradication of the tumor cells, which will be followed by the recovery of humoral
      immunity. Patients receiving the 19273-4SCAR T cells will be closely monitored for infusion
      response, tumor eradication effect, longevity of the CAR T cells, and the recovery of B cell
      functions after withdrawal of the CAR T cells.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with adverse events.
time frame: 2 years.
description: Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
measure: Survival time of Anti-CD19 CAR T cells in vivo.
time frame: 2 years.
description: Measure the survival of 4th generation CAR T cells transduced with the anti-CD19 lentiviral vector.
measure: Response rates to the 4th generation CAR T cells.
time frame: 2 years.
description: Describe the response rates of patients treated with 4th generation CAR T cells, including partial remission (PR), complete remission (CR), stable disease (SD) and progressive disease (PD).
measure: Survival time of the patients.
time frame: 2 years.
description: Evaluate the survival time of the patients treated with the 4th generation CAR T cells, including progression free survival (PFS) and overall survival (OS).
arm group label: CAR T cells
arm group type: Experimental
description: Autologous 4th generation anti-CD19-CAR T cells
intervention type: Genetic
intervention name: Anti-CD19 CAR T cells
description: Autologous 4th generation withdrawable lentiviral-transduced anti-CD19-CAR T cells
arm group label: CAR T cells
other name: 19273-4SCAR
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jun Zhu, MD
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
last name: Jun Zhu, MD
phone: +86-10-88196596
email: zj@bjcancer.org
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University
investigator full name: Jun Zhu
investigator title: Director
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell