<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/NCT04450069</url>
  </required_header>
  <id_info>
    <org_study_id>CBR-sCAR19-3001</org_study_id>
    <nct_id>NCT04450069</nct_id>
  </id_info>
  <brief_title>CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies</brief_title>
  <official_title>A Phase 1, Open-label, Dose Escalating Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the Combination of CLBR001 and SWI019 in Patients With Relapsed/Refractory B-cell Malignancies</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>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>
      CLBR001 + SWI019 is an combination investigational immunotherapy being evaluated as a&#xD;
      potential treatment for patients diagnosed with B cell malignancies who are refractory or&#xD;
      unresponsive to salvage therapy or who cannot be considered for or have progressed after&#xD;
      autologous hematopoietic cell transplantation. This first-in-human study will assess the&#xD;
      safety and tolerability of CLBR001 + SWI019 and is designed to determine the maximum&#xD;
      tolerated dose (MTD) or optimal SWI019 dose (OSD). Patients will be administered a single&#xD;
      infusion of CLBR001 cells followed by cycles of SWI019. The study will also assess the&#xD;
      pharmacokinetics and pharmacodynamics of CLBR001 + SWI019.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CLBR001 + SWI019 is a two-component therapy comprising an autologous chimeric antigen&#xD;
      receptor T (CAR-T) cell product (CLBR001, the switchable CAR-T cell (sCAR-T)) and an&#xD;
      anti-CD19 (cluster of differentiation antigen 19) antibody (SWI019, the switch, a biologic).&#xD;
      In combination, SWI019 acts as an adapter molecule that controls the activity of the CLBR001&#xD;
      CAR-T cell product.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events</measure>
    <time_frame>35 days</time_frame>
    <description>To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of first cycle dose limiting toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum drug concentration (Cmax) of SWI019</measure>
    <time_frame>up to Day 35</time_frame>
    <description>To determine the maximum concentration of SWI019 in a patient's peripheral blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) of SWI019</measure>
    <time_frame>up to Day 35</time_frame>
    <description>To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach Cmax (Tmax) of SWI019</measure>
    <time_frame>up to Day 35</time_frame>
    <description>To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL) of SWI019</measure>
    <time_frame>up to Day 35</time_frame>
    <description>To determine the clearance factor of SWI019 in a patient's peripheral blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent elimination half-life (t1/2) of SWI019</measure>
    <time_frame>up to Day 35</time_frame>
    <description>To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of CLBR001 cells in peripheral blood</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To quantify CLBR001 in a patient's peripheral blood at different time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenic response to CLBR001</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenic response to SWI019</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum cytokine concentrations</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To measure the cytokine levels (e.g. TNFa, IL-6, IL-1, IL-2, etc.) in a patient's peripheral blood at different time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To evaluate the duration of patient's progression-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>To evaluate the overall duration of patient's survival</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</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>Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>CLBR001 and SWI019</intervention_name>
    <description>Investigational immunotherapy for B cell malignancies</description>
    <arm_group_label>Dose Escalation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with relapsed / refractory previously treated B cell malignancies (according&#xD;
             to the World Health Organization classification; 2017)&#xD;
&#xD;
          -  Patients must have received adequate prior therapy including at least two lines of&#xD;
             prior therapies including anthracycline or bendamustine-containing chemotherapy,&#xD;
             anti-CD20 (cluster of differentiation antigen 20) therapies and/or Brutton's tyrosine&#xD;
             kinase (BTK) inhibitors&#xD;
&#xD;
          -  Patients treated with prior CD19 targeted molecules (e.g., Blincyto) must have&#xD;
             confirmed CD19+ disease&#xD;
&#xD;
          -  Patients must be ineligible for allogeneic stem cell transplant (SCT)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1&#xD;
&#xD;
          -  Estimated life expectancy of ≥ 12 weeks from the first day of SWI019 dose administered&#xD;
&#xD;
          -  Willing to undergo pre- and post-treatment core needle biopsy&#xD;
&#xD;
          -  Adequate hematological, renal, pulmonary, cardiac, and liver function&#xD;
&#xD;
          -  Resolved adverse events of any prior therapy to either baseline or CTCAE Grade ≤1&#xD;
&#xD;
          -  Women of childbearing potential, a negative pregnancy test and must agree to practice&#xD;
             effective birth control&#xD;
&#xD;
          -  Men sexually active with female partners of child bearing potential must agree to&#xD;
             practice effective contraception&#xD;
&#xD;
          -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests and&#xD;
             other procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with certain disease histologies including pediatric&#xD;
             lymphomas/leukemias, monoclonal gammopathy of undetermined significance (MGUS), T-cell&#xD;
             histiocyte large B cell lymphoma&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Active bacterial, viral, and fungal infections&#xD;
&#xD;
          -  History of allogeneic stem cell transplantation&#xD;
&#xD;
          -  Treatment with any prior lentiviral or retroviral based CAR-T&#xD;
&#xD;
          -  Patients receiving live (attenuated) vaccines within 4 weeks of screening visit or&#xD;
             need for live vaccine on study&#xD;
&#xD;
          -  Patients with known active central nervous system (CNS) disease. Patients with prior&#xD;
             CNS disease that has been effectively treated may be eligible&#xD;
&#xD;
          -  History of Class III or IV New York Heart Association (NYHA) heart failure, myocardial&#xD;
             infarction, unstable angina or other significant cardiac disease within 6 months of&#xD;
             screening&#xD;
&#xD;
          -  Involvement of cardiac tissue by lymphoma&#xD;
&#xD;
          -  Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP)&#xD;
&#xD;
          -  HIV-1 and HIV-2 antibody positive patients&#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>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 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>CD19 CAR-T Cell</keyword>
  <keyword>Blood Cancer</keyword>
  <keyword>Hematological malignancy</keyword>
  <keyword>Neoplasms</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>Neoplasms</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/NCT04450069
org study id: CBR-sCAR19-3001
nct id: NCT04450069
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
CLBR001 + SWI019 is an combination investigational immunotherapy being evaluated as a
      potential treatment for patients diagnosed with B cell malignancies who are refractory or
      unresponsive to salvage therapy or who cannot be considered for or have progressed after
      autologous hematopoietic cell transplantation. This first-in-human study will assess the
      safety and tolerability of CLBR001 + SWI019 and is designed to determine the maximum
      tolerated dose (MTD) or optimal SWI019 dose (OSD). Patients will be administered a single
      infusion of CLBR001 cells followed by cycles of SWI019. The study will also assess the
      pharmacokinetics and pharmacodynamics of CLBR001 + SWI019.
CLBR001 + SWI019 is a two-component therapy comprising an autologous chimeric antigen
      receptor T (CAR-T) cell product (CLBR001, the switchable CAR-T cell (sCAR-T)) and an
      anti-CD19 (cluster of differentiation antigen 19) antibody (SWI019, the switch, a biologic).
      In combination, SWI019 acts as an adapter molecule that controls the activity of the CLBR001
      CAR-T cell product.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
time frame: 35 days
description: To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
measure: Number of first cycle dose limiting toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
time frame: up to 1 year
description: Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD)
measure: Maximum drug concentration (Cmax) of SWI019
time frame: up to Day 35
description: To determine the maximum concentration of SWI019 in a patient's peripheral blood
measure: Area under the curve (AUC) of SWI019
time frame: up to Day 35
description: To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
measure: Time to reach Cmax (Tmax) of SWI019
time frame: up to Day 35
description: To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood
measure: Clearance (CL) of SWI019
time frame: up to Day 35
description: To determine the clearance factor of SWI019 in a patient's peripheral blood
measure: Apparent elimination half-life (t1/2) of SWI019
time frame: up to Day 35
description: To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood
measure: Quantification of CLBR001 cells in peripheral blood
time frame: up to 1 year
description: To quantify CLBR001 in a patient's peripheral blood at different time points
measure: Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies
time frame: up to 1 year
description: To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry
measure: Immunogenic response to CLBR001
time frame: up to 1 year
description: To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
measure: Immunogenic response to SWI019
time frame: up to 1 year
description: To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
measure: Serum cytokine concentrations
time frame: up to 1 year
description: To measure the cytokine levels (e.g. TNFa, IL-6, IL-1, IL-2, etc.) in a patient's peripheral blood at different time points
measure: Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria
time frame: up to 1 year
description: To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
measure: Duration of response (DOR)
time frame: up to 1 year
description: To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
measure: Progression free survival (PFS)
time frame: up to 1 year
description: To evaluate the duration of patient's progression-free survival
measure: Overall survival (OS)
time frame: up to 1 year
description: To evaluate the overall duration of patient's survival
arm group label: Dose Escalation
arm group type: Experimental
description: CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)
intervention type: Combination Product
intervention name: CLBR001 and SWI019
description: Investigational immunotherapy for B cell malignancies
arm group label: Dose Escalation
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: Neoplasms
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