<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/NCT04456023</url>
  </required_header>
  <id_info>
    <org_study_id>CCTL019C2203</org_study_id>
    <nct_id>NCT04456023</nct_id>
  </id_info>
  <brief_title>Study of Tisagenlecleucel in Chinese Adult Patients With Relapsed or Refractory Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL)</brief_title>
  <official_title>A Phase II, Single-arm, Multicenter Trial to Evaluate the Efficacy and Safety of Tisagenlecleucel in Chinese Adult Patients With Relapsed or Refractory Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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>
      This is a multi-center, phase II study to evaluate the efficacy and safety of CTL019 in&#xD;
      Chinese adult patients with relapsed or refractory DLBCL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Disease assessments will be performed at screening, after bridging, 1, 3, 6, 9 and 12 months&#xD;
      after tisagenlecleucel infusion, and every 6 months in the second year, and annually up to 60&#xD;
      months after infusion. Efficacy will be assessed until progression; safety will be assessed&#xD;
      throughout the study. A long term follow-up up to 15 years after CTL019 infusion will&#xD;
      continue under a separate protocol (CCTL019A2205B)(NCT02445222).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    This study was cancelled before enrolling any patients for business related reasons.&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 31, 2022</start_date>
  <completion_date type="Anticipated">September 27, 2027</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2022</primary_completion_date>
  <phase>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>Overall Response Rate (ORR)</measure>
    <time_frame>From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months</time_frame>
    <description>Complete Response (CR) and Partial Response (PR) according to the Lugano classification as determined by the Investigator.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months</time_frame>
    <description>Time from CR or PR, whichever occurs first, to relapse or death due to DLBCL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months</time_frame>
    <description>Time from tisagenlecleucel infusion to CR or PR, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months</time_frame>
    <description>Time from tisagenlecleucel infusion to the first documented disease progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event free survival (EFS)</measure>
    <time_frame>From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months</time_frame>
    <description>Time from tisagenlecleucel infusion to the first documented disease progression or relapse, new treatment for lymphoma or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months</time_frame>
    <description>Time from tisagenlecleucel infusion to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths</measure>
    <time_frame>From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months</time_frame>
    <description>Analysis of absolute and relative frequencies for treatment emergent AE, SAE and Deaths by primary System Organ Class (SOC) through the monitoring of relevant clinical and laboratory safety parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tisagenlecleucel immunogenicity (humoral)</measure>
    <time_frame>Up to Month 60</time_frame>
    <description>The humoral immunogenicity assay will be evaluated to measure the antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tisagenlecleucel immunogenicity (cellular)</measure>
    <time_frame>Up to Month 60</time_frame>
    <description>The cellular immunogenicity assay will be evaluated to assess the presence of T lymphocytes activated by the tisagenlecleucel protein.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In vivo cellular PK profile of tisagenelecleucel</measure>
    <time_frame>Up to Month 60</time_frame>
    <description>qPCR and flow cytometry to measure tisagenlecleucel transgene concentration in blood, bone marrow and other matrices/tissues.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS</measure>
    <time_frame>Up to Day 7 after tocilizumab infusion</time_frame>
    <description>Concentration of Tocilizumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum cytokines (IL-10, interferon gamma, IL-6, CRP and ferritin)</measure>
    <time_frame>Up to Month 60</time_frame>
    <description>Concentration of soluble factors (IL-10, interferon gamma, IL-6, CRP and ferritin) will be listed and summarized by participant and time point.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Diffuse Large B-Cell Lymphoma (DLBCL)</condition>
  <arm_group>
    <arm_group_label>Tisagenlecleucel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tisagenlecleucel</intervention_name>
    <description>A single intravenous (i.v.) infusion of 0.6 - 6.0×10^8 CAR positive viable T cells.</description>
    <arm_group_label>Tisagenlecleucel</arm_group_label>
    <other_name>CTL019</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent must be obtained prior to participation in the study&#xD;
&#xD;
          2. Patients must be ≥18 years of age at the time of ICF signature&#xD;
&#xD;
          3. Histologically confirmed DLBCL at last relapse (including DLBCL transformed from&#xD;
             follicular lymphoma and double-triple hit lymphoma)&#xD;
&#xD;
          4. Relapsed or refractory disease after at least 2 lines of systemic therapy, including&#xD;
             anti-CD20 antibody and an anthracycline, or having failed or being ineligible for&#xD;
             autologous HSCT&#xD;
&#xD;
          5. ECOG performance status that is either 0 or 1 at screening&#xD;
&#xD;
          6. Measurable disease at time of enrollment:&#xD;
&#xD;
               -  Nodal lesions greater than 15 mm in the long axis, regardless of the length of&#xD;
                  the short axis or&#xD;
&#xD;
               -  Extra nodal lesion (outside lymph node or nodal mass, but including liver and&#xD;
                  spleen) at least 10 mm in long and short axis&#xD;
&#xD;
          7. Adequate organ function&#xD;
&#xD;
          8. Must have a leukapheresis material of non-mobilized cells available for manufacturing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene&#xD;
             therapy product&#xD;
&#xD;
          2. Primary mediastinal large B-cell lymphoma, EBV+ DLBCL, Richter's transformation,&#xD;
             Burkitt lymphoma, primary DLBCL of CNS, T cell / histiocyte rich large B-cell&#xD;
             lymphoma, primary cutaneous DLBCL.&#xD;
&#xD;
          3. Eligible for and consenting to autologous HSCT&#xD;
&#xD;
          4. Prior allogeneic SCT&#xD;
&#xD;
          5. Active CNS involvement by disease under study, except if the CNS involvement has been&#xD;
             effectively treated (i.e. patient is asymptomatic) and local treatment was greater&#xD;
             than 4 weeks before enrollment&#xD;
&#xD;
          6. Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre&#xD;
             syndrome)&#xD;
&#xD;
          7. Investigational medicinal product within the last 30 days or five half-lives&#xD;
             (whichever is longer) prior to screening&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>February 25, 2022</last_update_submitted>
  <last_update_submitted_qc>February 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diffuse Large B-cell Lymphoma</keyword>
  <keyword>double/triple hit lymphoma</keyword>
  <keyword>relapsed/refractory</keyword>
  <keyword>tisagenlecleucel</keyword>
  <keyword>CTL019</keyword>
  <keyword>Chinese</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</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>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
    <ipd_url>https://www.clinicalstudydatarequest.com</ipd_url>
  </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/NCT04456023
org study id: CCTL019C2203
nct id: NCT04456023
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multi-center, phase II study to evaluate the efficacy and safety of CTL019 in
      Chinese adult patients with relapsed or refractory DLBCL.
Disease assessments will be performed at screening, after bridging, 1, 3, 6, 9 and 12 months
      after tisagenlecleucel infusion, and every 6 months in the second year, and annually up to 60
      months after infusion. Efficacy will be assessed until progression; safety will be assessed
      throughout the study. A long term follow-up up to 15 years after CTL019 infusion will
      continue under a separate protocol (CCTL019A2205B)(NCT02445222).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR)
time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
description: Complete Response (CR) and Partial Response (PR) according to the Lugano classification as determined by the Investigator.
measure: Duration of Response (DOR)
time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
description: Time from CR or PR, whichever occurs first, to relapse or death due to DLBCL.
measure: Time to response (TTR)
time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
description: Time from tisagenlecleucel infusion to CR or PR, whichever occurs first.
measure: Progression-Free Survival (PFS)
time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
description: Time from tisagenlecleucel infusion to the first documented disease progression or death due to any cause.
measure: Event free survival (EFS)
time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
description: Time from tisagenlecleucel infusion to the first documented disease progression or relapse, new treatment for lymphoma or death due to any cause.
measure: Overall Survival (OS)
time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
description: Time from tisagenlecleucel infusion to death due to any cause.
measure: Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths
time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
description: Analysis of absolute and relative frequencies for treatment emergent AE, SAE and Deaths by primary System Organ Class (SOC) through the monitoring of relevant clinical and laboratory safety parameters.
measure: Tisagenlecleucel immunogenicity (humoral)
time frame: Up to Month 60
description: The humoral immunogenicity assay will be evaluated to measure the antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.
measure: Tisagenlecleucel immunogenicity (cellular)
time frame: Up to Month 60
description: The cellular immunogenicity assay will be evaluated to assess the presence of T lymphocytes activated by the tisagenlecleucel protein.
measure: In vivo cellular PK profile of tisagenelecleucel
time frame: Up to Month 60
description: qPCR and flow cytometry to measure tisagenlecleucel transgene concentration in blood, bone marrow and other matrices/tissues.
measure: Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS
time frame: Up to Day 7 after tocilizumab infusion
description: Concentration of Tocilizumab
measure: Serum cytokines (IL-10, interferon gamma, IL-6, CRP and ferritin)
time frame: Up to Month 60
description: Concentration of soluble factors (IL-10, interferon gamma, IL-6, CRP and ferritin) will be listed and summarized by participant and time point.
arm group label: Tisagenlecleucel
arm group type: Experimental
description: All patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel.
intervention type: Biological
intervention name: Tisagenlecleucel
description: A single intravenous (i.v.) infusion of 0.6 - 6.0×10^8 CAR positive viable T cells.
arm group label: Tisagenlecleucel
other name: CTL019
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Tisagenlecleucel
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
ipd url: https://www.clinicalstudydatarequest.com