<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/NCT04488354</url>
  </required_header>
  <id_info>
    <org_study_id>CBR-sCAR19-3002</org_study_id>
    <nct_id>NCT04488354</nct_id>
  </id_info>
  <brief_title>Long-term Follow-up Study for Patients Treated With CLBR001 CAR-T</brief_title>
  <official_title>A Study to Evaluate the Long-Term Safety of CLBR001, A Lentiviral Based Chimeric Antigen Receptor, In Patients With B-Cell Malignancies Previously Administered CLBR001</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Calibr, a division of Scripps Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Calibr, a division of Scripps Research</source>
  <oversight_info>
    <has_dmc>No</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 study is designed as a long-term follow-up study of participants who have receive&#xD;
      genetically modified autologous CLBR001 CAR-T cells&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be enrolled following either the completion or early&#xD;
      termination/discontinuation from Study NCT04450069 or any protocol in which patients were&#xD;
      administered CLBR001. Patients will begin the long-term follow-up period regardless of&#xD;
      whether they responded to treatment or progressed on treatment. Patients will be followed for&#xD;
      up to 15 years post CLBR001 infusion and will continue to be monitored for safety,&#xD;
      immunogenicity, and efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">January 21, 2021</start_date>
  <completion_date type="Anticipated">August 2036</completion_date>
  <primary_completion_date type="Anticipated">August 2036</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>Incidence and duration of new adverse events, late onset adverse events, and events of special interest</measure>
    <time_frame>15 years</time_frame>
    <description>To measure the incidence and duration of new adverse events, late onset adverse events, and events of special interest</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and duration of new serious adverse events</measure>
    <time_frame>15 years</time_frame>
    <description>To measure the incidence and duration of new serious adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of patients with resolution of adverse events, serious adverse events, and duration that began in previous treatment protocols of CLBR001</measure>
    <time_frame>15 years</time_frame>
    <description>The measure the incidence of patients with resolution of adverse events, serious adverse events, and duration that began in previous treatment protocols of CLBR001</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of new malignancies</measure>
    <time_frame>15 years</time_frame>
    <description>The measure the incidence of new malignancies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response</measure>
    <time_frame>15 years</time_frame>
    <description>To evaluate clinical efficacy by measuring the overall response by Response Evaluation Criteria In Lymphoma (RECIL) 2017</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>15 years</time_frame>
    <description>To evaluate clinical efficacy by measuring the duration of response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>15 years</time_frame>
    <description>To evaluate clinical efficacy by measuring progression free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients undergoing stem cell transplant</measure>
    <time_frame>15 years</time_frame>
    <description>To evaluate the proportion of patients undergoing stem cell transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of CLBR001 CAR+ cells in blood, bone marrow and/or tissue specimens</measure>
    <time_frame>3, 6, 9,12 and 24 months</time_frame>
    <description>To measure the number of CLBR001 CAR+ cells in blood, bone marrow and/or tissue specimens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detectable replication competent lentivirus (RCL)</measure>
    <time_frame>15 years</time_frame>
    <description>To measure detectable replication competent lentivirus (RCL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Titer of anti-drug antibody (ADA) for CLBR001 and SWI019</measure>
    <time_frame>3, 6, 12 months</time_frame>
    <description>To evaluate immunogenicity by measuring the titer of ADA for CLBR001 and SWI019</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of detection of ADA for CLBR001 and SWI019</measure>
    <time_frame>3, 6, 12 months</time_frame>
    <description>To evaluate immunogenicity by measuring the duration of detection of ADA for CLBR001 and SWI019</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Relapsed/Refractory B-cell Lymphomas</condition>
  <condition>Diffuse Large B-Cell Lymphoma (DLBCL)</condition>
  <condition>Follicular Lymphoma (FL)</condition>
  <condition>Chronic Lymphocytic Leukemia (CLL)</condition>
  <condition>Marginal Zone Lymphoma (MZL)</condition>
  <condition>Mantle Cell Lymphoma (MCL)</condition>
  <condition>Small Lymphocytic Lymphoma (SLL)</condition>
  <condition>Primary Mediastinal Large B Cell Lymphoma</condition>
  <condition>Transformed Follicular Lymphoma</condition>
  <condition>Waldenstrom Macroglobulinemia</condition>
  <condition>Lymphoplasmacytic Lymphoma</condition>
  <condition>Burkitt Lymphoma</condition>
  <arm_group>
    <arm_group_label>CLBR001 treated patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who have been administered with CLBR001</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>CLBR001 and SWI019</intervention_name>
    <description>No study drug is administered in this study. Patients who have received CLBR001 autologous CAR-T cells will be evaluated in this trial for long-term safety and efficacy</description>
    <arm_group_label>CLBR001 treated patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients who received at least one CLBR001 cell dose and have either discontinued&#xD;
             early or completed the core treatment protocol or any protocol such as a managed&#xD;
             access protocol as applicable.&#xD;
&#xD;
          -  Subject is willing and able to adhere to the study visit schedule and other protocol&#xD;
             requirements.&#xD;
&#xD;
          -  Capable of giving signed informed consent which includes compliance with the&#xD;
             requirements and restrictions listed in the informed consent form (ICF) and in this&#xD;
             protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  There are no specific exclusion criteria for this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Masonic Cancer Center, University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College - New York Presbyterian Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest Baptist Health</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute - Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute - Texas Transplant Institute</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS, Hardy IR, Schulman A, Du J, Wang F, Singer O, Ma J, Nunez V, Shen J, Woods AK, Wright TM, Schultz PG, Kim CH, Young TS. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E459-68. doi: 10.1073/pnas.1524155113. Epub 2016 Jan 12.</citation>
    <PMID>26759369</PMID>
  </reference>
  <reference>
    <citation>Viaud S, Ma JSY, Hardy IR, Hampton EN, Benish B, Sherwood L, Nunez V, Ackerman CJ, Khialeeva E, Weglarz M, Lee SC, Woods AK, Young TS. Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory. Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10898-E10906. doi: 10.1073/pnas.1810060115. Epub 2018 Oct 29.</citation>
    <PMID>30373813</PMID>
  </reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>June 27, 2023</last_update_submitted>
  <last_update_submitted_qc>June 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CAR-T Cell Therapy</keyword>
  <keyword>Switchable CAR-T Cell</keyword>
  <keyword>Autologous Cell Therapy</keyword>
  <keyword>CD19 Positive Disease</keyword>
  <keyword>Blood Cancer</keyword>
  <keyword>Hematological malignancy</keyword>
  <keyword>Neoplasms</keyword>
  <keyword>CD19 CAR-T Cell</keyword>
  <keyword>Long Term Follow Up (LTFU)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burkitt Lymphoma</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
  </condition_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/NCT04488354
org study id: CBR-sCAR19-3002
nct id: NCT04488354
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is designed as a long-term follow-up study of participants who have receive
      genetically modified autologous CLBR001 CAR-T cells
Patients will be enrolled following either the completion or early
      termination/discontinuation from Study NCT04450069 or any protocol in which patients were
      administered CLBR001. Patients will begin the long-term follow-up period regardless of
      whether they responded to treatment or progressed on treatment. Patients will be followed for
      up to 15 years post CLBR001 infusion and will continue to be monitored for safety,
      immunogenicity, and efficacy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence and duration of new adverse events, late onset adverse events, and events of special interest
time frame: 15 years
description: To measure the incidence and duration of new adverse events, late onset adverse events, and events of special interest
measure: Incidence and duration of new serious adverse events
time frame: 15 years
description: To measure the incidence and duration of new serious adverse events
measure: Incidence of patients with resolution of adverse events, serious adverse events, and duration that began in previous treatment protocols of CLBR001
time frame: 15 years
description: The measure the incidence of patients with resolution of adverse events, serious adverse events, and duration that began in previous treatment protocols of CLBR001
measure: Incidence of new malignancies
time frame: 15 years
description: The measure the incidence of new malignancies
measure: Overall response
time frame: 15 years
description: To evaluate clinical efficacy by measuring the overall response by Response Evaluation Criteria In Lymphoma (RECIL) 2017
measure: Duration of response
time frame: 15 years
description: To evaluate clinical efficacy by measuring the duration of response
measure: Progression free survival
time frame: 15 years
description: To evaluate clinical efficacy by measuring progression free survival
measure: Proportion of patients undergoing stem cell transplant
time frame: 15 years
description: To evaluate the proportion of patients undergoing stem cell transplant
measure: Number of CLBR001 CAR+ cells in blood, bone marrow and/or tissue specimens
time frame: 3, 6, 9,12 and 24 months
description: To measure the number of CLBR001 CAR+ cells in blood, bone marrow and/or tissue specimens
measure: Detectable replication competent lentivirus (RCL)
time frame: 15 years
description: To measure detectable replication competent lentivirus (RCL)
measure: Titer of anti-drug antibody (ADA) for CLBR001 and SWI019
time frame: 3, 6, 12 months
description: To evaluate immunogenicity by measuring the titer of ADA for CLBR001 and SWI019
measure: Duration of detection of ADA for CLBR001 and SWI019
time frame: 3, 6, 12 months
description: To evaluate immunogenicity by measuring the duration of detection of ADA for CLBR001 and SWI019
arm group label: CLBR001 treated patients
arm group type: Experimental
description: Patients who have been administered with CLBR001
intervention type: Combination Product
intervention name: CLBR001 and SWI019
description: No study drug is administered in this study. Patients who have received CLBR001 autologous CAR-T cells will be evaluated in this trial for long-term safety and efficacy
arm group label: CLBR001 treated patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS, Hardy IR, Schulman A, Du J, Wang F, Singer O, Ma J, Nunez V, Shen J, Woods AK, Wright TM, Schultz PG, Kim CH, Young TS. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E459-68. doi: 10.1073/pnas.1524155113. Epub 2016 Jan 12.
PMID: 26759369
citation: Viaud S, Ma JSY, Hardy IR, Hampton EN, Benish B, Sherwood L, Nunez V, Ackerman CJ, Khialeeva E, Weglarz M, Lee SC, Woods AK, Young TS. Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory. Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10898-E10906. doi: 10.1073/pnas.1810060115. Epub 2018 Oct 29.
PMID: 30373813
responsible party type: Sponsor
mesh term: Burkitt Lymphoma
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, B-Cell
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Waldenstrom Macroglobulinemia
sharing ipd: No