<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/NCT04464200</url>
  </required_header>
  <id_info>
    <org_study_id>20-167</org_study_id>
    <nct_id>NCT04464200</nct_id>
  </id_info>
  <brief_title>19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers</brief_title>
  <official_title>A Phase I Study of CD19-Targeted 19(T2)28z1xx Chimeric Antigen Receptor (CAR) Modified T Cells in Adult Patients With Relapsed or Refractory B-cell Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test the safety of 19(T2)28z1xx CAR T cells in people with&#xD;
      relapsed/refractory B-cell cancers. The researchers will try to find the highest dose of&#xD;
      19(T2)28z1xx CAR T cells that causes few or mild side effects in participants. Once they find&#xD;
      this dose, they can test it in future participants to see if it is effective in treating&#xD;
      their relapsed/refractory B-cell cell cancers. This study will also look at whether&#xD;
      19(T2)28z1xx CAR T cells work against participants' cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 6, 2020</start_date>
  <completion_date type="Anticipated">July 2026</completion_date>
  <primary_completion_date type="Anticipated">July 2026</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a standard phase I open-label dose-escalation trial. Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the MTD. There are 4 planned dose levels with one additional de-escalation dose level. A 3+3 design will be used to establish the RP2D. Once the RP2D is determined, the study will open to Dose Expansion phase and up to 12 patients with B-cell non-Hodgkin lymphoma (same eligibility criteria as the dose-escalation phase).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recommended Phase II Dose (RP2D)</measure>
    <time_frame>28 days post infusion</time_frame>
    <description>Dose escalation will use a 3+3 design. DLT-evaluable participants are defined as those participants who were infused with 19(T2)28z1XX CAR T cells and who were monitored for toxicities during the first 28 days of post infusion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall response rate (ORR)</measure>
    <time_frame>2 years</time_frame>
    <description>Response and progression of the disease will be evaluated in this study using the Lugano Classification</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <condition>Primary Mediastinal Large B Cell Lymphoma</condition>
  <condition>Transformed Follicular Lymphoma to Diffuse Large B Cell Lymphoma</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Indolent Non-Hodgkin Lymphoma</condition>
  <condition>Marginal Zone Lymphoma</condition>
  <condition>Waldenstrom Macroglobulinemia</condition>
  <condition>Burkitt's Lymphoma</condition>
  <condition>Primary CNS Lymphoma</condition>
  <arm_group>
    <arm_group_label>19(T2)28z1xx CAR T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the RP2D. There are 4 planned flat-dose levels: 25x10^6, 50 x 10^6, 100 x 10^6 and 200 x 10^6 CAR T cells and one de-escalation dose: 12.5 x 10^6 CAR T cells. A standard 3+3 dose escalation design will be implemented starting from dose 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>19(T2)28z1xx CAR T cells</intervention_name>
    <description>2-7 days following the completion of the conditioning chemotherapy, patients will receive the CAR- T cells by IV infusion over 1-3 days depending on the dose level and formulation of the final CAR- T cells.</description>
    <arm_group_label>19(T2)28z1xx CAR T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years of age&#xD;
&#xD;
          -  Creatinine ≤2.0 mg/100 ml, direct bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x upper&#xD;
             limit of normal (ULN)&#xD;
&#xD;
          -  Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse&#xD;
             oximetry.&#xD;
&#xD;
          -  Histologically confirmed DLBCL and large B cell lymphoma, including&#xD;
&#xD;
               -  DLBCL, not otherwise specified (NOS), or&#xD;
&#xD;
               -  Transformed DLBCL from follicular lymphoma, or&#xD;
&#xD;
               -  High-grade B cell lymphoma (excluding Burkitt's lymphoma), or&#xD;
&#xD;
               -  Primary mediastinal large B cell lymphoma AND&#xD;
&#xD;
               -  Chemotherapy refractory disease, defined as a failure to achieve at least a&#xD;
                  partial response or disease progression within 12 months to the last therapy, OR&#xD;
&#xD;
               -  Disease progression or recurrence in ≤12 months of prior autologous stem cell&#xD;
                  transplant (ASCT), OR&#xD;
&#xD;
               -  Relapsed disease after 2 or more prior chemoimmunotherapies with at least one&#xD;
                  containing an anthracycline and CD20 directed therapy&#xD;
&#xD;
          -  Patients need to have radiographically documented disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ECOG performance status ≥2.&#xD;
&#xD;
          -  Patients with active CNS disease&#xD;
&#xD;
          -  Pregnant or lactating women. Women and men of childbearing age should use effective&#xD;
             contraception while on this study and continue for 1 year after all treatment is&#xD;
             finished.&#xD;
&#xD;
          -  Impaired cardiac function (LVEF &lt;40%) as assessed by ECHO or MUGA scan.&#xD;
&#xD;
          -  Patients with the following cardiac conditions will be excluded:&#xD;
&#xD;
               -  New York Heart Association (NYHA) stage III or IV congestive heart failure&#xD;
&#xD;
               -  Myocardial infarction ≤6 months prior to enrollment&#xD;
&#xD;
               -  History of clinically significant ventricular arrhythmia or unexplained syncope,&#xD;
                  not believed to be vasovagal in nature or due to dehydration ≤6 months prior to&#xD;
                  enrollment&#xD;
&#xD;
          -  Patients with HIV or active hepatitis B or hepatitis C infection are ineligible.&#xD;
&#xD;
          -  Patients with prior allogeneic hematopoietic stem cell transplant are eligible, if&#xD;
             more than 3 months from transplant and if patients have no active graft versus host&#xD;
             disease (GvHD) and not on systemic immunosuppressive therapy.&#xD;
&#xD;
          -  Prior CD19-directed therapy including CD19 CAR T cells is allowed, as long as&#xD;
             expression of CD19 is confirmed by flow cytometry or immunohistochemistry.&#xD;
&#xD;
          -  Patients with uncontrolled systemic fungal, bacterial, viral or other infection are&#xD;
             ineligible.&#xD;
&#xD;
          -  Patients with any concurrent active malignancies as defined by malignancies requiring&#xD;
             any therapy other than expectant observation or hormonal therapy, with the exception&#xD;
             of squamous and basal cell carcinoma of the skin.&#xD;
&#xD;
          -  Patients with presence of clinically significant neurological disorders such as&#xD;
             epilepsy, generalized seizure disorder, severe brain injuries are ineligible.&#xD;
&#xD;
          -  Any other issue which, in the opinion of the treating physician, would make the&#xD;
             patient ineligible for the 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>
  <overall_official>
    <last_name>Jae Park, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth (Limited Protocol Activities)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen (Limited Protocol Activities)</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Commack - Suffolk (Limited Protocol Activities)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester (Limited Protocol Activities)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau (Limited Protocol Activities)</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>August 22, 2023</last_update_submitted>
  <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>19(T2)28z1XX CAR T cells</keyword>
  <keyword>20-167</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, B-Cell</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
  </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/NCT04464200
org study id: 20-167
nct id: NCT04464200
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test the safety of 19(T2)28z1xx CAR T cells in people with
      relapsed/refractory B-cell cancers. The researchers will try to find the highest dose of
      19(T2)28z1xx CAR T cells that causes few or mild side effects in participants. Once they find
      this dose, they can test it in future participants to see if it is effective in treating
      their relapsed/refractory B-cell cell cancers. This study will also look at whether
      19(T2)28z1xx CAR T cells work against participants' cancer.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a standard phase I open-label dose-escalation trial. Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the MTD. There are 4 planned dose levels with one additional de-escalation dose level. A 3+3 design will be used to establish the RP2D. Once the RP2D is determined, the study will open to Dose Expansion phase and up to 12 patients with B-cell non-Hodgkin lymphoma (same eligibility criteria as the dose-escalation phase).
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended Phase II Dose (RP2D)
time frame: 28 days post infusion
description: Dose escalation will use a 3+3 design. DLT-evaluable participants are defined as those participants who were infused with 19(T2)28z1XX CAR T cells and who were monitored for toxicities during the first 28 days of post infusion.
measure: overall response rate (ORR)
time frame: 2 years
description: Response and progression of the disease will be evaluated in this study using the Lugano Classification
arm group label: 19(T2)28z1xx CAR T cells
arm group type: Experimental
description: Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the RP2D. There are 4 planned flat-dose levels: 25x10^6, 50 x 10^6, 100 x 10^6 and 200 x 10^6 CAR T cells and one de-escalation dose: 12.5 x 10^6 CAR T cells. A standard 3+3 dose escalation design will be implemented starting from dose 1.
intervention type: Drug
intervention name: 19(T2)28z1xx CAR T cells
description: 2-7 days following the completion of the conditioning chemotherapy, patients will receive the CAR- T cells by IV infusion over 1-3 days depending on the dose level and formulation of the final CAR- T cells.
arm group label: 19(T2)28z1xx CAR T cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jae Park, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Burkitt Lymphoma
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Waldenstrom Macroglobulinemia
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.