<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/NCT04419909</url>
  </required_header>
  <id_info>
    <org_study_id>UPCC 40419</org_study_id>
    <secondary_id>834286</secondary_id>
    <nct_id>NCT04419909</nct_id>
  </id_info>
  <brief_title>Retreatment With CTL019/CTL119</brief_title>
  <official_title>Retreatment With CTL019/CTL119 in Patients With Late Relapse of B-Cell Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is designed to evaluate the effects of retreatment with CTL019/CTL119 in&#xD;
      patients with late relapse of B-cell lymphomas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single arm open label trial that will assess the safety and efficacy of retreatment&#xD;
      with CTL019/CTL119 chimeric antigen receptor (CAR) modified T cells in patients who have late&#xD;
      relapse of diffuse large B-cell or follicular lymphoma after achieving complete remission&#xD;
      from prior CTL019/CTL119 treatment. Patients eligible for this protocol will have been&#xD;
      treated initially with CTL019/CTL119 under UPCC13413/NCT02030834, have experienced a durable&#xD;
      complete response (defined as ≥ 6 months duration), and have a residual manufactured&#xD;
      CTL019/CTL119 product available. This protocol will serve subjects with no available&#xD;
      potentially curative treatment options (such as autologous or allogeneic stem cell&#xD;
      transplantation) who have a limited prognosis (months to &lt; 2 year expected survival) with&#xD;
      available therapies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">May 2024</start_date>
  <completion_date type="Anticipated">July 2027</completion_date>
  <primary_completion_date type="Anticipated">July 2027</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>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>At time of consent through 1 year after the subject received CTL019/CTL119</time_frame>
    <description>Safety of retreatment with CTL019/CTL119 as measured by treatment-related events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate using Cheson 2007 criteria</measure>
    <time_frame>Month 3 post-infusion</time_frame>
    <description>Efficacy of retreatment with CTL019/CTL119 as measured by ORR by Cheson 2007 definitions at 3 months</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Lymphoma, B-Cell</condition>
  <arm_group>
    <arm_group_label>Retreatment with CTL019/CTL119</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will receive retreatment with CTL019/CTL119 and be followed per the schedule of procedures.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CD19 redirected autologous T cells (CTL019 or CTL119 cells)</intervention_name>
    <description>Retreatment with CD19-directed Chimeric Antigen Receptor-modified T Cells (CART19 cells) or huCD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19 cells) in subjects with late relapse of B-cell lymphomas.</description>
    <arm_group_label>Retreatment with CTL019/CTL119</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diffuse Large B-Cell Lymphoma or Follicular lymphoma, previously identified as CD19+&#xD;
&#xD;
          2. Previously treated on UPCC13413/ NCT02030834 with CTL019/CTL119, with historical&#xD;
             manufactured product available at Penn for reinfusion&#xD;
&#xD;
          3. Previous complete response to CAR T-cells with a duration ≥ 6 months (defined as 168&#xD;
             days)&#xD;
&#xD;
          4. No available curative treatment options (such as autologous or allogeneic HSCT) with&#xD;
             limited prognosis (several months to &lt; 2 year survival) with currently available&#xD;
             therapies.&#xD;
&#xD;
          5. Age ≥18 years&#xD;
&#xD;
          6. Creatinine &lt; 1.6 mg/dL&#xD;
&#xD;
          7. ALT/AST &lt; 3x upper limit of normal&#xD;
&#xD;
          8. Bilirubin &lt; 2.0 mg/dL, unless subject has Gilbert's Syndrome (≤3.0 mg/dL)&#xD;
&#xD;
          9. Measurable or assessable disease according to the &quot;Revised Response Criteria for&#xD;
             Malignant Lymphoma&quot; (Cheson et al., J. Clin. Onc., 2007)88. Patients in complete&#xD;
             remission with no evidence of disease are not eligible.&#xD;
&#xD;
         10. Performance status (ECOG) 0 or 1.&#xD;
&#xD;
         11. Left Ventricle Ejection Fraction (LVEF) &gt; 40% confirmed by ECHO/MUGA&#xD;
&#xD;
         12. Agree to contraceptive requirements outlined in Section 4.3.&#xD;
&#xD;
         13. Provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Uncontrolled active infection.&#xD;
&#xD;
          2. Active hepatitis B or hepatitis C infection.&#xD;
&#xD;
          3. Any uncontrolled active medical disorder that would preclude participation as&#xD;
             outlined.&#xD;
&#xD;
          4. Class III/IV cardiovascular disability according to the New York Heart Association&#xD;
             Classification (see Appendix 1).&#xD;
&#xD;
          5. HIV infection.&#xD;
&#xD;
          6. Patients with active CNS involvement by malignancy. Patients with prior CNS disease&#xD;
             that has been effectively treated will be eligible providing treatment was &gt;4 weeks&#xD;
             before enrollment&#xD;
&#xD;
          7. Patients with a known history or prior diagnosis of optic neuritis or other&#xD;
             immunologic or inflammatory disease affecting the central nervous system.&#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>Stephen J Schuster</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Stephen J Schuster, MD</last_name>
    <phone>215.614.1846</phone>
    <email>schustes@pennmedicine.upenn.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emerging Medicine</last_name>
    <phone>855-216-0098</phone>
    <email>PennCancerTrials@careboxhealth.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Stephen J Schuster, MD</last_name>
      <phone>855-216-0098</phone>
      <email>PennCancerTrials@careboxhealth.com</email>
    </contact>
    <contact_backup>
      <last_name>Emerging Medicine</last_name>
      <phone>855-216-0098</phone>
      <email>PennCancerTrials@careboxhealth.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CTL019</keyword>
  <keyword>CTL119</keyword>
  <keyword>CAR T-cell</keyword>
  <keyword>CART</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tisagenlecleucel</mesh_term>
  </intervention_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/NCT04419909
org study id: UPCC 40419
secondary id: 834286
nct id: NCT04419909
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study is designed to evaluate the effects of retreatment with CTL019/CTL119 in
      patients with late relapse of B-cell lymphomas.
This is a single arm open label trial that will assess the safety and efficacy of retreatment
      with CTL019/CTL119 chimeric antigen receptor (CAR) modified T cells in patients who have late
      relapse of diffuse large B-cell or follicular lymphoma after achieving complete remission
      from prior CTL019/CTL119 treatment. Patients eligible for this protocol will have been
      treated initially with CTL019/CTL119 under UPCC13413/NCT02030834, have experienced a durable
      complete response (defined as ≥ 6 months duration), and have a residual manufactured
      CTL019/CTL119 product available. This protocol will serve subjects with no available
      potentially curative treatment options (such as autologous or allogeneic stem cell
      transplantation) who have a limited prognosis (months to < 2 year expected survival) with
      available therapies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
time frame: At time of consent through 1 year after the subject received CTL019/CTL119
description: Safety of retreatment with CTL019/CTL119 as measured by treatment-related events
measure: Overall response rate using Cheson 2007 criteria
time frame: Month 3 post-infusion
description: Efficacy of retreatment with CTL019/CTL119 as measured by ORR by Cheson 2007 definitions at 3 months
arm group label: Retreatment with CTL019/CTL119
arm group type: Experimental
description: All subjects will receive retreatment with CTL019/CTL119 and be followed per the schedule of procedures.
intervention type: Drug
intervention name: CD19 redirected autologous T cells (CTL019 or CTL119 cells)
description: Retreatment with CD19-directed Chimeric Antigen Receptor-modified T Cells (CART19 cells) or huCD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19 cells) in subjects with late relapse of B-cell lymphomas.
arm group label: Retreatment with CTL019/CTL119
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stephen J Schuster
role: Principal Investigator
affiliation: University of Pennsylvania
last name: Stephen J Schuster, MD
phone: 215.614.1846
email: schustes@pennmedicine.upenn.edu
last name: Emerging Medicine
phone: 855-216-0098
email: PennCancerTrials@careboxhealth.com
facility: 
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Tisagenlecleucel
sharing ipd: No