<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/NCT03019055</url>
  </required_header>
  <id_info>
    <org_study_id>PRO00028724</org_study_id>
    <nct_id>NCT03019055</nct_id>
  </id_info>
  <brief_title>Study of CAR-20/19-T Cells in Patients With Relapsed Refractory B Cell</brief_title>
  <official_title>Phase 1/1b Study of Redirected Autologous T Cells Engineered to Contain an Anti CD19 and Anti CD20 scFv Coupled to CD3ζ and 4-1BB Signaling Domains in Patients With Relapsed and/or Refractory CD19 or CD20 Positive B Cell Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical College of Wisconsin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's Hospital and Health System Foundation, Wisconsin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical College of Wisconsin</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 is a phase 1/1b, interventional single arm, open label, treatment study designed to&#xD;
      evaluate the safety and feasibility of infusion of autologous T cells engineered to contain&#xD;
      an anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20)&#xD;
      single chain variable fragment (scFv) coupled to cluster of differentiation CD3ζ (CD3ζ) and&#xD;
      co-stimulatory domain 4-1BB (4-1BB) signaling domains in patients with relapsed and/or&#xD;
      refractory CD19 or CD20 positive B cell malignancies&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, single arm, open label phase I/1b study to demonstrate the&#xD;
      feasibility of manufacturing CAR-T cells expressing tandem receptors against both CD20 and&#xD;
      CD19 (CAR-20/19-T) in a completely closed system using the CliniMACS Prodigy device and then&#xD;
      determine the safety of this dual targeted CAR in a first-in-human study of patients with&#xD;
      relapsed and refractory B cell malignancies. Secondary outcomes will include response rates,&#xD;
      and observed toxicities of the treatment, specifically the development of cytokine release&#xD;
      syndrome (CRS), an inflammatory storm that has been seen with previous CAR-T therapies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2017</start_date>
  <completion_date type="Actual">August 24, 2021</completion_date>
  <primary_completion_date type="Actual">October 1, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>The study is divided into two phases. Phase 1 and Phase 1b. Phase 1: consists of 2 cohorts; dose escalation and dose expansion. The CAR-T cells were given over 2 days.&#xD;
In the phase 1 portion, there will be a dose escalation cohort to determine the safe CAR-20/19-T cell dose in patients with CLL/SLL and NHL. Once the desired dose has been identified there will be a 6 patient dose expansion phase at the specified dose level.&#xD;
Phase 1b: In the Phase 1b portion of the study, we will test the safety of unfractionated CAR-T cells utilizing the safe dose identified in the phase 1 portion (2.5 x 10^6 cells/kg).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Adverse Events After CAR 20/19-T Cell Infusion</measure>
    <time_frame>28 days after infusion</time_frame>
    <description>This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 4.03) occurring within the first 28 days following infusion.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Lymphoma, Non-Hodgkin</condition>
  <condition>Lymphoma, B-Cell</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <arm_group>
    <arm_group_label>CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)</intervention_name>
    <description>CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 0: 2.5 x10^5 CAR-20/19-T cells/kg (starting dose level)</description>
    <arm_group_label>CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)</intervention_name>
    <description>CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 1: 7.5 x10^5 CAR-20/19-T cells/kg</description>
    <arm_group_label>CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)</intervention_name>
    <description>CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 2: 2.5 x10^6 CAR-20/19-T cells/kg (goal cell dose)&#xD;
Phase 1b Expansion Dose Level: 2.5 x 10^6 cells/kg (single infusion)</description>
    <arm_group_label>CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)</intervention_name>
    <description>CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.</description>
    <arm_group_label>CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Diagnosis of B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) /&#xD;
             small lymphocytic leukemia (SLL): Patients must be aged≥18 years with relapsed,&#xD;
             refractory disease and no available curative options that meet clinical criteria to&#xD;
             initiate treatment.&#xD;
&#xD;
          2. Patients with B-cell NHL or CLL/SLL must have either CD19 or CD20 positive disease on&#xD;
             most recent biopsy performed (a repeat biopsy is not mandatory for this study except&#xD;
             as noted below). A minimum of 5% CD19 or CD20 positivity by immunohistochemistry or&#xD;
             flow cytometry on prior or repeat biopsy is required.&#xD;
&#xD;
          3. Absolute CD3+ T cell count ≥50/mm^3.&#xD;
&#xD;
          4. MRI brain and Lumbar Puncture with cerebral spinal fluid (CSF) analysis by cytology&#xD;
             and flow cytometry without evidence of central nervous system (CNS) involvement only&#xD;
             in patients with history of CNS involvement.&#xD;
&#xD;
          5. Measurable disease must have been documented within 4 weeks of the time of consent&#xD;
             defined as the following by disease specific subtype:&#xD;
&#xD;
               1. B-cell NHL: Active disease defined as nodal lesions greater than 20 mm in the&#xD;
                  long axis or extranodal lesions &gt;10 mm in long and short axis or bone marrow&#xD;
                  involvement that is biopsy proven.&#xD;
&#xD;
               2. CLL/SLL: Active disease by either bone marrow, peripheral flow cytometry, or CT&#xD;
                  and/or positron emission tomography (PET) imaging with nodal disease.&#xD;
&#xD;
          6. Patients should have failed at least two lines of a standard treatment and meet&#xD;
             disease specific criteria detailed below:&#xD;
&#xD;
               1. CLL/SLL: measurable disease as defined above that has relapsed after at least one&#xD;
                  line of chemo-immunotherapy and progressed or intolerant to ibrutinib&#xD;
                  monotherapy.&#xD;
&#xD;
               2. CD19 or CD20 positive B cell NHL limited to the following histologies: Advanced&#xD;
                  Stage III or IV Follicular Lymphoma, Diffuse Large B cell Lymphoma and associated&#xD;
                  subtypes (e.g. aggressive B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma,&#xD;
                  primary mediastinal B-cell lymphoma, Epstein Barr virus positive diffuse large&#xD;
                  B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal&#xD;
                  zone lymphoma, and Richter's transformation) and Mantle cell lymphoma. Specific&#xD;
                  criteria include:&#xD;
&#xD;
                    -  Patients must have active, measurable disease after two lines of cytotoxic&#xD;
                       chemotherapy of which one must be anthracycline containing.&#xD;
&#xD;
                    -  Must have received Rituximab or another CD20 antibody and at minimum two&#xD;
                       chemotherapy regimens appropriate for their disease.&#xD;
&#xD;
                    -  Either failed autologous transplant or ineligible to receive autologous&#xD;
                       transplant&#xD;
&#xD;
          7. Karnofsky performance score ≥70. See Appendix A for scales.&#xD;
&#xD;
          8. Normal Baseline Neurological Evaluation: Mini-Mental Status Exam Score 24-30.&#xD;
&#xD;
          9. Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine&#xD;
             aminotransferase (ALT) &lt;5 x upper limit of normal (ULN); serum bilirubin and alkaline&#xD;
             phosphatase &lt;5 x ULN, or considered not clinically significant as per the clinical PIs&#xD;
             discretion (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to&#xD;
             underlying disease.&#xD;
&#xD;
         10. Adequate renal function, defined as creatinine clearance&gt;60 ml/min&#xD;
&#xD;
         11. Able to provide written informed consent.&#xD;
&#xD;
         12. Agree to practice birth control during the study.&#xD;
&#xD;
         13. Adequate cardiac function as indicated by New York Heart Association (NYHA)&#xD;
             classification I or II AND left ventricular ejection fraction of ≥35% (by&#xD;
             echocardiogram or MUGA) and adequate pulmonary function as indicated by room air&#xD;
             oxygen saturation of ≥92%.&#xD;
&#xD;
         14. Expected survival &gt;12 weeks.&#xD;
&#xD;
         15. Negative urine or serum pregnancy test in females of child bearing potential at study&#xD;
             entry and again within 48 hours' prior lymphodepleting chemotherapy.&#xD;
&#xD;
         16. Patients with prior blinatumomab treatment require repeat biopsy post-blinatumomab&#xD;
             treatment that demonstrates CD19 or CD20 positive disease.&#xD;
&#xD;
         17. Meet criteria for regarding fertility and contraception.&#xD;
&#xD;
         18. Central line access will be required for CAR-20/19-T cell infusion.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Positive beta-human chorionic gonadotropin in females of child-bearing potential.&#xD;
&#xD;
          2. Patients with known systemic allergy to bovine or murine products.&#xD;
&#xD;
          3. Known prior positive serology for human anti-mouse antibody (HAMA).&#xD;
&#xD;
          4. Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.&#xD;
&#xD;
          5. History of significant autoimmune disease OR active, uncontrolled autoimmune&#xD;
             phenomenon: such as systemic lupus erythematous, Wegner's glomerulonephritis,&#xD;
             autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring&#xD;
             steroid therapy defined as &gt;20 mg of prednisone or equivalent daily.&#xD;
&#xD;
          6. Presence of ≥grade 3 non-hematologic toxicities as per CTCAE version 5.0 from any&#xD;
             previous treatment unless it is felt to be due to underlying disease.&#xD;
&#xD;
          7. Concurrent use of investigational therapeutic agents or enrollment on another&#xD;
             therapeutic clinical trial at any institution. Minimum of ≥4 weeks required from&#xD;
             administration of any other investigational agents on other clinical trials prior to&#xD;
             enrollment on this CAR-T protocol.&#xD;
&#xD;
          8. Refusal to participate in the long-term follow-up protocol.&#xD;
&#xD;
          9. Patients with active CNS involvement by malignancy on MRI or by lumbar puncture.&#xD;
&#xD;
             a. Patients with prior CNS disease that has been effectively treated will be eligible&#xD;
             providing treatment was &gt;4 weeks before enrollment and a remission documented within 8&#xD;
             weeks of planned CAR-T cell infusion by MRI brain and CSF analysis.&#xD;
&#xD;
         10. Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are&#xD;
             excluded if they are &lt;100 days' post-transplant, have evidence of active&#xD;
             graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.&#xD;
&#xD;
         11. Previous CAR-T cell therapy directed at either CD19 or CD20 within 100 days of planned&#xD;
             CAR-20/19-T cell infusion (does not include re-enrollment)&#xD;
&#xD;
             a. Patients with prior CAR-T treatment against CD19 or CD20 must have repeat biopsy&#xD;
             confirming a minimum of 5% CD19 or CD20 positivity by immunohistochemistry or flow&#xD;
             cytometry.&#xD;
&#xD;
         12. Anti-CD20 antibody treatment within 4 weeks of cell infusion.&#xD;
&#xD;
         13. Anti-CD19 antibody treatment within 4 weeks of cell infusion.&#xD;
&#xD;
         14. Cytotoxic chemotherapy other than lymphodepletion within 14 days of CAR-T cell&#xD;
             infusion.&#xD;
&#xD;
         15. Cytotoxic chemotherapy treatment within 14 days or steroid treatment (other than&#xD;
             replacement dose steroids) within 7 days prior to apheresis collection for CAR-T&#xD;
             cells.&#xD;
&#xD;
         16. Patients post solid organ transplant who develop high grade lymphomas or leukemias.&#xD;
&#xD;
         17. Concurrent active malignancy other than basal or squamous cell carcinomas of the skin.&#xD;
&#xD;
        Special Criteria for regarding Fertility and Contraception&#xD;
&#xD;
        Female subjects of reproductive potential (women who have reached menarche or women who&#xD;
        have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses&#xD;
        within the preceding 24 months, or have not undergone a sterilization procedure&#xD;
        [hysterectomy or bilateral oophorectomy]) must have a negative serum or urine pregnancy&#xD;
        test performed as part of eligibility criteria and again within 48 hours of initiation of&#xD;
        lymphodepleting chemotherapy.&#xD;
&#xD;
        Due to the high-risk level of this study, while enrolled, all subjects must agree not to&#xD;
        participate in a conception process (e.g., active attempt to become pregnant or to&#xD;
        impregnate, sperm donation, in vitro fertilization). Additionally, if participating in&#xD;
        sexual activity that could lead to pregnancy, the study subject must agree to use reliable&#xD;
        and double barrier methods of contraception during the follow-up period of the protocol.&#xD;
&#xD;
        Acceptable birth control includes a combination of two of the following methods:&#xD;
&#xD;
          -  Condoms* (male or female) with or without a spermicidal agent.&#xD;
&#xD;
          -  Diaphragm or cervical cap with spermicide&#xD;
&#xD;
          -  Intrauterine device (IUD)&#xD;
&#xD;
          -  Hormonal-based contraception Subjects who are not of reproductive potential (women who&#xD;
             are premenarche or have been post-menopausal for at least 24 consecutive months or&#xD;
             have undergone hysterectomy tubal ligation, salpingectomy, and/or bilateral&#xD;
             oophorectomy or men who have documented azoospermia) are eligible without requiring&#xD;
             the use of contraception.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nirav Shah, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Froedtert Hospital &amp; Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <results_first_submitted>April 12, 2021</results_first_submitted>
  <results_first_submitted_qc>May 6, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 7, 2021</results_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical College of Wisconsin</investigator_affiliation>
    <investigator_full_name>Nirav Shah</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>CAR-T</keyword>
  <keyword>Chimeric antigen receptor T-cell therapy</keyword>
  <keyword>CAR Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03019055/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 9, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03019055/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Of 31 enrolled subjects who signed the informed consent form, 26 met all eligibility criteria.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>CAR-20/19-T Cells (1.0 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 0: 2.5 x10^5 CAR-20/19-T cells/kg (starting dose level)</description>
        </group>
        <group group_id="P2">
          <title>CAR-20/19-T Cells (2.5 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 1: 7.5 x10^5 CAR-20/19-T cells/kg</description>
        </group>
        <group group_id="P3">
          <title>CAR-20/19-T Cells (7.5 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 2: 2.5 x10^6 CAR-20/19-T cells/kg (goal cell dose)&#xD;
Phase 1b Expansion Dose Level: 2.5 x 10^6 cells/kg (single infusion)</description>
        </group>
        <group group_id="P4">
          <title>CAR-20/19-T Cells (2.5 x10^6 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Due to a lack of dose limiting toxicities at higher dosages, no subjects were enrolled in the 1.0x10^5 cell/kg dosage level.</population>
      <group_list>
        <group group_id="B1">
          <title>CAR-20/19-T Cells (1.0 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 0: 2.5 x10^5 CAR-20/19-T cells/kg (starting dose level)</description>
        </group>
        <group group_id="B2">
          <title>CAR-20/19-T Cells (2.5 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 1: 7.5 x10^5 CAR-20/19-T cells/kg</description>
        </group>
        <group group_id="B3">
          <title>CAR-20/19-T Cells (7.5 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 2: 2.5 x10^6 CAR-20/19-T cells/kg (goal cell dose)&#xD;
Phase 1b Expansion Dose Level: 2.5 x 10^6 cells/kg (single infusion)</description>
        </group>
        <group group_id="B4">
          <title>CAR-20/19-T Cells (2.5 x10^6 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="0"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="20"/>
            <count group_id="B5" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="52.33" spread="2.31"/>
                    <measurement group_id="B3" value="55.00" spread="8.19"/>
                    <measurement group_id="B4" value="55.85" spread="14.44"/>
                    <measurement group_id="B5" value="55.35" spread="12.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="20"/>
                    <measurement group_id="B5" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="16"/>
                    <measurement group_id="B5" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="20"/>
                    <measurement group_id="B5" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Adverse Events After CAR 20/19-T Cell Infusion</title>
        <description>This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 4.03) occurring within the first 28 days following infusion.</description>
        <time_frame>28 days after infusion</time_frame>
        <population>Of the eligible subjects, CAR cell product did not reach the required cell concentration for infusion for 4 subjects in the highest dosage level. These subjects were withdrawn by the investigator. Overall, 22 subjects received the investigational product in this study. The initial concentration for the study was 2.5x10^5 cells/kg. No dose limiting toxicities were experienced at this concentration and the reduced dose of 1.0x10^5 cells/kg was not used.</population>
        <group_list>
          <group group_id="O1">
            <title>CAR-20/19-T Cells (1.0 x10^5 CAR-20/19-T Cells/kg)</title>
            <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 0: 2.5 x10^5 CAR-20/19-T cells/kg (starting dose level)</description>
          </group>
          <group group_id="O2">
            <title>CAR-20/19-T Cells (2.5 x10^5 CAR-20/19-T Cells/kg)</title>
            <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 1: 7.5 x10^5 CAR-20/19-T cells/kg</description>
          </group>
          <group group_id="O3">
            <title>CAR-20/19-T Cells (7.5 x10^5 CAR-20/19-T Cells/kg)</title>
            <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 2: 2.5 x10^6 CAR-20/19-T cells/kg (goal cell dose)&#xD;
Phase 1b Expansion Dose Level: 2.5 x 10^6 cells/kg (single infusion)</description>
          </group>
          <group group_id="O4">
            <title>CAR-20/19-T Cells (2.5 x10^6 CAR-20/19-T Cells/kg)</title>
            <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Adverse Events After CAR 20/19-T Cell Infusion</title>
          <description>This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 4.03) occurring within the first 28 days following infusion.</description>
          <population>Of the eligible subjects, CAR cell product did not reach the required cell concentration for infusion for 4 subjects in the highest dosage level. These subjects were withdrawn by the investigator. Overall, 22 subjects received the investigational product in this study. The initial concentration for the study was 2.5x10^5 cells/kg. No dose limiting toxicities were experienced at this concentration and the reduced dose of 1.0x10^5 cells/kg was not used.</population>
          <units>Serious Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>28 days</time_frame>
      <desc>No subjects were enrolled in the 1.0x10^5 cells/kg dosage group.</desc>
      <group_list>
        <group group_id="E1">
          <title>CAR-20/19-T Cells (1.0 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 0: 2.5 x10^5 CAR-20/19-T cells/kg (starting dose level)</description>
        </group>
        <group group_id="E2">
          <title>CAR-20/19-T Cells (2.5 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 1: 7.5 x10^5 CAR-20/19-T cells/kg</description>
        </group>
        <group group_id="E3">
          <title>CAR-20/19-T Cells (7.5 x10^5 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.&#xD;
Phase 1 Dose Level 2: 2.5 x10^6 CAR-20/19-T cells/kg (goal cell dose)&#xD;
Phase 1b Expansion Dose Level: 2.5 x 10^6 cells/kg (single infusion)</description>
        </group>
        <group group_id="E4">
          <title>CAR-20/19-T Cells (2.5 x10^6 CAR-20/19-T Cells/kg)</title>
          <description>Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.&#xD;
CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (12.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Multi-organ failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Cytokine release syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (12.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="13" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="12" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="37" subjects_affected="14" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Disseminated intravascular coagulation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="15" subjects_affected="10" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Floaters</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="8" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="9" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="18" subjects_affected="11" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fecal incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="17" subjects_affected="11" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="7" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="20" subjects_affected="12" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Multi-organ failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Cytokine release syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="18" subjects_affected="13" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vascular access complication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="7" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="10" subjects_affected="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="10" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="17" subjects_affected="9" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="6" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="14" subjects_affected="8" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fibrinogen decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="8" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="15" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="49" subjects_affected="16" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="12" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="21" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="59" subjects_affected="16" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="12" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="11" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="32" subjects_affected="13" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="9" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="13" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="68" subjects_affected="16" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="8" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="14" subjects_affected="9" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="7" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="11" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="27" subjects_affected="10" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="27" subjects_affected="13" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="16" subjects_affected="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="7" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="8" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="21" subjects_affected="9" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Tumor lysis syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="10" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dysphasia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="11" subjects_affected="8" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Movements involuntary</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vasovagal reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Facial muscle weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hallucinations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Apnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="7" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="8" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="9" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="13" subjects_affected="8" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="15" subjects_affected="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Nirav Shah, MD</name_or_title>
      <organization>Froedtert Hospital and the Medical College of Wisconsin</organization>
      <phone>414-805-8900</phone>
      <email>cccto@mcw.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03019055
org study id: PRO00028724
nct id: NCT03019055
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 1/1b, interventional single arm, open label, treatment study designed to
      evaluate the safety and feasibility of infusion of autologous T cells engineered to contain
      an anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20)
      single chain variable fragment (scFv) coupled to cluster of differentiation CD3ζ (CD3ζ) and
      co-stimulatory domain 4-1BB (4-1BB) signaling domains in patients with relapsed and/or
      refractory CD19 or CD20 positive B cell malignancies
This is a single center, single arm, open label phase I/1b study to demonstrate the
      feasibility of manufacturing CAR-T cells expressing tandem receptors against both CD20 and
      CD19 (CAR-20/19-T) in a completely closed system using the CliniMACS Prodigy device and then
      determine the safety of this dual targeted CAR in a first-in-human study of patients with
      relapsed and refractory B cell malignancies. Secondary outcomes will include response rates,
      and observed toxicities of the treatment, specifically the development of cytokine release
      syndrome (CRS), an inflammatory storm that has been seen with previous CAR-T therapies.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: The study is divided into two phases. Phase 1 and Phase 1b. Phase 1: consists of 2 cohorts; dose escalation and dose expansion. The CAR-T cells were given over 2 days.
In the phase 1 portion, there will be a dose escalation cohort to determine the safe CAR-20/19-T cell dose in patients with CLL/SLL and NHL. Once the desired dose has been identified there will be a 6 patient dose expansion phase at the specified dose level.
Phase 1b: In the Phase 1b portion of the study, we will test the safety of unfractionated CAR-T cells utilizing the safe dose identified in the phase 1 portion (2.5 x 10^6 cells/kg).
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Adverse Events After CAR 20/19-T Cell Infusion
time frame: 28 days after infusion
description: This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 4.03) occurring within the first 28 days following infusion.
arm group label: CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)
arm group type: Experimental
description: Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
arm group label: CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)
arm group type: Experimental
description: Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
arm group label: CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)
arm group type: Experimental
description: Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
arm group label: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)
arm group type: Experimental
description: Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
intervention type: Biological
intervention name: CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)
description: CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.
Phase 1 Dose Level 0: 2.5 x10^5 CAR-20/19-T cells/kg (starting dose level)
arm group label: CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)
intervention type: Biological
intervention name: CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)
description: CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.
Phase 1 Dose Level 1: 7.5 x10^5 CAR-20/19-T cells/kg
arm group label: CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)
intervention type: Biological
intervention name: CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)
description: CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.
Phase 1 Dose Level 2: 2.5 x10^6 CAR-20/19-T cells/kg (goal cell dose)
Phase 1b Expansion Dose Level: 2.5 x 10^6 cells/kg (single infusion)
arm group label: CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)
intervention type: Biological
intervention name: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)
description: CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.
arm group label: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Nirav Shah, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Medical College of Wisconsin
investigator full name: Nirav Shah
investigator title: Associate Professor
mesh term: Lymphoma
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 