<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/NCT02222688</url>
  </required_header>
  <id_info>
    <org_study_id>#140141</org_study_id>
    <nct_id>NCT02222688</nct_id>
  </id_info>
  <brief_title>UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia</brief_title>
  <official_title>A Phase I Clinical Trial to Determine the Safety and Tolerability of UC-961 (Cirmtuzumab), an Anti-ROR1 Monoclonal Antibody, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia Who Are Ineligible for Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Kipps</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Diego</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>
      The purpose of the study is to investigate the safety of the investigational agent,&#xD;
      cirmtuzumab. Cirmtuzumab is a monoclonal antibody drug designed to attach to a protein,&#xD;
      called ROR1, on the surface of chronic lymphocytic leukemia (CLL) cells to block cell growth&#xD;
      and survival. ROR1 is rarely expressed on healthy cells so the idea is to preferentially get&#xD;
      rid of the cancer cells. Although there is evidence in laboratory animals that cirmtuzumab&#xD;
      can decrease the number of CLL cells, the investigators do not know if this will work in&#xD;
      humans. This drug will be given to humans for the first time in this study. Therefore, the&#xD;
      goal of this study is to see if cirmtuzumab is safe and tolerated in study participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a first in human, open-label single institution, Phase I dose escalation study of in&#xD;
      patients with relapsed or refractory CLL. Treatment cycle (14 days) will consist of&#xD;
      cirmtuzumab administered intravenously on a bi-weekly (every two weeks) schedule for a total&#xD;
      of 4 doses. Eight dose cohorts (of 3 to 6 patients in size) plus an expansion cohort of 6&#xD;
      patients are planned. In the first 4 dose cohorts, there is intra-patient dose escalation to&#xD;
      monitor for acute toxicities, such as tumor lysis syndrome.&#xD;
&#xD;
      A cycle may be repeated every 14 days if the patient has at least stable disease by clinical&#xD;
      examination (or interim response assessment) and has again met hematologic, renal, and&#xD;
      hepatic laboratory parameters as defined in the eligibility section, and is without ongoing&#xD;
      Grade 3 non-hematologic or Grade 4 hematologic toxicities attributable to cirmtuzumab. The&#xD;
      total duration of study drug administration is 4 cycles. Each cycle consists of clinical and&#xD;
      laboratory evaluation on Day 1 and safety assessments on Days 3 and 8.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 8, 2014</start_date>
  <completion_date type="Actual">May 1, 2018</completion_date>
  <primary_completion_date type="Actual">October 10, 2017</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab</measure>
    <time_frame>1 year</time_frame>
    <description>The MTD is defined as the highest dose studied at which no more than one in six patients experience a dose-limiting toxicity (DLT) during the DLT observation period. The biologically active dose will be determined at a dose below or equal to the MTD upon review of the the study data; the final determination will also consider any cumulative or delayed toxicity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>The DLT observation period is 56 days from the start of the first infusion for the intra-patient dosing cohorts and 28 days after the start of the first infusion for subsequent dosing cohorts</time_frame>
    <description>The occurrence of any of the following adverse events considered to be possibly, probably, or definitely related to cirmtuzumab within the DLT observation period (56 days from the first infusion for cohorts with intrapatient dose escalation, and 28 days of the start investigational treatment for cohorts without intrapatient dose escalation):&#xD;
Grade 3 or greater non-hematologic toxicity with the exception of Grade 3 infusion reaction.&#xD;
Grade 4 neutropenia lasting more than 5 days despite appropriate medical management.&#xD;
Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion.&#xD;
Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC).&#xD;
Grade 4 anemia unexplained by underlying disease.&#xD;
Any AE requiring a dose delay of greater than 14 days.&#xD;
Patients with baseline cytopenias or starting blood counts in the grade 2 range are evaluable for hematologic DLT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs.</measure>
    <time_frame>From the start of investigational treatment to completion of follow-up, an average of 33 weeks</time_frame>
    <description>Treatment emergent adverse events (description, timing, CTCAE grade, severity, seriousness, and relatedness)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria</measure>
    <time_frame>From baseline visit to response assessment visit at 56 days after final cirmtuzumab infusion, an average of 52 days</time_frame>
    <description>Clinical response [stable disease (SD) or progressive disease (PD)] defined by iwCLL criteria including clinical, hematological, and bone marrow features for a period of at least 2 months from completion of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival as Determined by iwCLL Criteria</measure>
    <time_frame>From start of treatment until objective tumor progression or death</time_frame>
    <description>The duration of time from the start of study treatment until objective tumor progression or death</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>Cirmtuzumab 0.015 - 0.03 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cirmtuzumab 0.5 - 1.0 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cirmtuzumab 2.0 - 4.0 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cirmtuzumab 8 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cirmtuzumab 16 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cirmtuzumab 20 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cirmtuzumab</intervention_name>
    <arm_group_label>Cirmtuzumab 0.015 - 0.03 mg/kg</arm_group_label>
    <arm_group_label>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</arm_group_label>
    <arm_group_label>Cirmtuzumab 0.5 - 1.0 mg/kg</arm_group_label>
    <arm_group_label>Cirmtuzumab 16 mg/kg</arm_group_label>
    <arm_group_label>Cirmtuzumab 2.0 - 4.0 mg/kg</arm_group_label>
    <arm_group_label>Cirmtuzumab 20 mg/kg</arm_group_label>
    <arm_group_label>Cirmtuzumab 8 mg/kg</arm_group_label>
    <other_name>UC-961</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
          -  Clinical and phenotypic verification of B cell CLL and measurable disease.&#xD;
             Immunophenotyping of the leukemic cells must demonstrate a monoclonal B cell&#xD;
             population with immunophenotype consistent with CLL.&#xD;
&#xD;
          -  Relapsed or refractory disease, defined by failure to achieve a partial response&#xD;
             within 6 months of initiation of therapy, or a 50% increase of baseline disease&#xD;
             measurements after achieving a clinical response.&#xD;
&#xD;
          -  Not amenable to approved therapies.&#xD;
&#xD;
          -  Prior Therapy: Must have progressed after purine-analog or alkylator based therapy, or&#xD;
             be considered inappropriate for chemo-immunotherapy due to one of the following:&#xD;
&#xD;
               -  Del 17p, which is associated with poor response to chemo-immunotherapy, or&#xD;
&#xD;
               -  Age greater than 70, or&#xD;
&#xD;
               -  Age greater than 65 with one of the following:&#xD;
&#xD;
               -  Grade ≥ 3 neutropenia, anemia, or thrombocytopenia attributable to cumulative&#xD;
                  myelotoxicity from prior administration of cytotoxic agents (as documented by&#xD;
                  bone marrow biopsy obtained since last prior therapy), or&#xD;
&#xD;
               -  Clinically apparent autoimmune cytopenia which may be exacerbated by fludarabine&#xD;
                  therapy, or&#xD;
&#xD;
               -  Estimated creatinine clearance (eCCr) &lt;70 mL/min (as determined by the&#xD;
                  Cockcroft-Gault method), or&#xD;
&#xD;
               -  Eastern Cooperative Oncology Group (ECOG) performance status greater than 0.&#xD;
&#xD;
          -  Has recovered from the toxic effects of prior therapy to their clinical baseline.&#xD;
&#xD;
          -  Women of childbearing potential must agree not to become pregnant for the duration of&#xD;
             the study. Both men and women must agree to use a barrier method of contraception for&#xD;
             the duration of the study and until 10 weeks after the final dose of cirmtuzumab.&#xD;
&#xD;
          -  Subjects must have at least one of the following indications for treatment:&#xD;
&#xD;
               -  Symptomatic or progressive splenomegaly;&#xD;
&#xD;
               -  Symptomatic lymph nodes, nodal clusters, or progressive lymphadenopathy;&#xD;
&#xD;
               -  Progressive anemia (hemoglobin ≤ 11 g/dL);&#xD;
&#xD;
               -  Progressive thrombocytopenia (platelets ≤ 100 x 10^9/L);&#xD;
&#xD;
               -  Weight loss &gt; 10% body weight over the preceding 6 month period;&#xD;
&#xD;
               -  Fatigue attributable to CLL;&#xD;
&#xD;
               -  Fever or night sweats for &gt; 2 weeks without evidence of infection;&#xD;
&#xD;
               -  Progressive lymphocytosis with an increase of &gt; 50% over a 2-month period or an&#xD;
                  anticipated doubling time of less than 12 months.&#xD;
&#xD;
          -  Subjects must have an ECOG performance status of 0-2.&#xD;
&#xD;
          -  Adequate hematologic function&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Adequate hepatic function&#xD;
&#xD;
          -  Adequate coagulation tests&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Pregnant or breast-feeding women will not be entered on this study due to risks of&#xD;
             fetal and teratogenic adverse events as seen in animal/human studies.&#xD;
&#xD;
          -  Patients who are currently receiving another investigational agent are excluded.&#xD;
&#xD;
          -  Patients who have had chemotherapy (e.g., purine analogues, alkylating agents),&#xD;
             immunotherapy, radiation therapy, or participation in any investigational drug&#xD;
             treatment within 4 weeks of initiation of UC-961 or at any time during the study.&#xD;
&#xD;
          -  Patients who have had prior (within 8 weeks of initiation of UC-961) or concurrent&#xD;
             antibody therapy directed against CLL (i.e., Rituxan® and Campath®).&#xD;
&#xD;
          -  Current infection requiring parenteral antibiotics.&#xD;
&#xD;
          -  Active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).&#xD;
&#xD;
          -  Concurrent malignancy or prior malignancy within the previous 3 years (other than&#xD;
             completely resected carcinoma in situ, prostate cancer, or localized non-melanoma skin&#xD;
             cancer).&#xD;
&#xD;
          -  Known central nervous system (CNS) involvement by malignancy.&#xD;
&#xD;
          -  Untreated autoimmunity such as autoimmune hemolytic anemia, or immune&#xD;
             thrombocytopenia.&#xD;
&#xD;
          -  Uncompensated hypothyroidism (defined as thyroid-stimulating hormone (TSH) greater&#xD;
             than 2x upper limit of normal not treated with replacement hormone).&#xD;
&#xD;
          -  Presence of more than 55% pro-lymphocytes in peripheral blood. Patients with Richter's&#xD;
             transformation are not excluded.&#xD;
&#xD;
          -  Insufficient recovery from surgical-related trauma or wound healing.&#xD;
&#xD;
          -  Impaired cardiac function including any of the following:&#xD;
&#xD;
               -  Myocardial infarction within 6 months of starting study drug;&#xD;
&#xD;
               -  A past medical history of clinically significant ECG abnormalities, including QTc&#xD;
                  481 milliseconds or greater;&#xD;
&#xD;
               -  Other clinically significant heart disease (e.g., congestive heart failure,&#xD;
                  uncontrolled hypertension, history of labile hypertension, or history of poor&#xD;
                  compliance with an antihypertensive regimen).&#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>Catriona Jamieson, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael Choi, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calilfornia Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSD Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Choi MY, Widhopf GF 2nd, Ghia EM, Kidwell RL, Hasan MK, Yu J, Rassenti LZ, Chen L, Chen Y, Pittman E, Pu M, Messer K, Prussak CE, Castro JE, Jamieson C, Kipps TJ. Phase I Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia. Cell Stem Cell. 2018 Jun 1;22(6):951-959.e3. doi: 10.1016/j.stem.2018.05.018.</citation>
    <PMID>29859176</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <results_first_submitted>June 19, 2019</results_first_submitted>
  <results_first_submitted_qc>July 29, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 13, 2020</results_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Thomas Kipps</investigator_full_name>
    <investigator_title>Deputy Director of Research Operations, Moores Cancer Center</investigator_title>
  </responsible_party>
  <keyword>cancer</keyword>
  <keyword>CLL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
  </condition_browse>
  <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 25, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT02222688/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were enrolled into the study between August 2014 and September 2017 and included patients seen in the UCSD Health system.</recruitment_details>
      <pre_assignment_details>Twenty-seven subjects were treated with cirmtuzumab and are included in the primary outcome analysis. One subject was enrolled into the trial twice; first in Cohort 1 and then again in Cohort 4 and is counted once for reporting of the baseline characteristics.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cirmtuzumab 0.015 - 0.03 mg/kg</title>
          <description>Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion</description>
        </group>
        <group group_id="P2">
          <title>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</title>
          <description>Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion</description>
        </group>
        <group group_id="P3">
          <title>Cirmtuzumab 0.5 - 1.0 mg/kg</title>
          <description>Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion</description>
        </group>
        <group group_id="P4">
          <title>Cimrtuzumab 2.0 - 4.0 mg/kg</title>
          <description>Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion</description>
        </group>
        <group group_id="P5">
          <title>Cirmtuzumab 8 mg/kg</title>
          <description>Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion</description>
        </group>
        <group group_id="P6">
          <title>Cirmtuzumab 16 mg/kg</title>
          <description>Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
        </group>
        <group group_id="P7">
          <title>Cirmtuzumab 20 mg/kg</title>
          <description>Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Twenty-seven subjects were treated with cirmtuzumab and are included in the primary outcome analysis. One subject was enrolled into the trial twice; first in Cohort 1 and then again in Cohort 4 and is counted twice for the baseline characteristics.</population>
      <group_list>
        <group group_id="B1">
          <title>Cirmtuzumab 0.015 - 0.03 mg/kg</title>
          <description>Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion</description>
        </group>
        <group group_id="B2">
          <title>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</title>
          <description>Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion</description>
        </group>
        <group group_id="B3">
          <title>Cirmtuzumab 0.5 - 1.0 mg/kg</title>
          <description>Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion</description>
        </group>
        <group group_id="B4">
          <title>Cirmtuzumab 2.0 - 4.0 mg/kg</title>
          <description>Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion</description>
        </group>
        <group group_id="B5">
          <title>Cirmtuzumab 8 mg/kg</title>
          <description>Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion</description>
        </group>
        <group group_id="B6">
          <title>Cirmtuzumab 16 mg/kg</title>
          <description>Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
        </group>
        <group group_id="B7">
          <title>Cirmtuzumab 20 mg/kg</title>
          <description>Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)</description>
        </group>
        <group group_id="B8">
          <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="4"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="3"/>
            <count group_id="B6" value="3"/>
            <count group_id="B7" value="6"/>
            <count group_id="B8" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="1"/>
                    <measurement group_id="B8" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="5"/>
                    <measurement group_id="B8" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="B1" value="72.75" spread="1.5"/>
                    <measurement group_id="B2" value="70.67" spread="11.68"/>
                    <measurement group_id="B3" value="66.67" spread="3.51"/>
                    <measurement group_id="B4" value="69.4" spread="7.23"/>
                    <measurement group_id="B5" value="70" spread="2.65"/>
                    <measurement group_id="B6" value="71.67" spread="9.29"/>
                    <measurement group_id="B7" value="77.33" spread="8.78"/>
                    <measurement group_id="B8" value="71.81" spread="7.32"/>
                  </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="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="4"/>
                    <measurement group_id="B8" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="2"/>
                    <measurement group_id="B8" value="14"/>
                  </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="B1" value="0"/>
                    <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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" 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="B1" value="0"/>
                    <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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <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 group_id="B6" value="1"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="1"/>
                  </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="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab</title>
        <description>The MTD is defined as the highest dose studied at which no more than one in six patients experience a dose-limiting toxicity (DLT) during the DLT observation period. The biologically active dose will be determined at a dose below or equal to the MTD upon review of the the study data; the final determination will also consider any cumulative or delayed toxicity.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>All participants who received any treatment with cirmtuzumab</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab</title>
          <description>The MTD is defined as the highest dose studied at which no more than one in six patients experience a dose-limiting toxicity (DLT) during the DLT observation period. The biologically active dose will be determined at a dose below or equal to the MTD upon review of the the study data; the final determination will also consider any cumulative or delayed toxicity.</description>
          <units>mg/kg</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Rate of Dose Limiting Toxicities (DLTs)</title>
        <description>The occurrence of any of the following adverse events considered to be possibly, probably, or definitely related to cirmtuzumab within the DLT observation period (56 days from the first infusion for cohorts with intrapatient dose escalation, and 28 days of the start investigational treatment for cohorts without intrapatient dose escalation):&#xD;
Grade 3 or greater non-hematologic toxicity with the exception of Grade 3 infusion reaction.&#xD;
Grade 4 neutropenia lasting more than 5 days despite appropriate medical management.&#xD;
Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion.&#xD;
Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC).&#xD;
Grade 4 anemia unexplained by underlying disease.&#xD;
Any AE requiring a dose delay of greater than 14 days.&#xD;
Patients with baseline cytopenias or starting blood counts in the grade 2 range are evaluable for hematologic DLT.</description>
        <time_frame>The DLT observation period is 56 days from the start of the first infusion for the intra-patient dosing cohorts and 28 days after the start of the first infusion for subsequent dosing cohorts</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cirmtuzumab 0.015 - 0.03 mg/kg</title>
            <description>Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</title>
            <description>Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O3">
            <title>Cirmtuzumab 0.5 - 1.0 mg/kg</title>
            <description>Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O4">
            <title>Cirmtuzumab 2.0 - 4.0 mg/kg</title>
            <description>Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O5">
            <title>Cirmtuzumab 8 mg/kg</title>
            <description>Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O6">
            <title>Cirmtuzumab 16 mg/kg</title>
            <description>Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
          </group>
          <group group_id="O7">
            <title>Cirmtuzumab 20 mg/kg</title>
            <description>Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Dose Limiting Toxicities (DLTs)</title>
          <description>The occurrence of any of the following adverse events considered to be possibly, probably, or definitely related to cirmtuzumab within the DLT observation period (56 days from the first infusion for cohorts with intrapatient dose escalation, and 28 days of the start investigational treatment for cohorts without intrapatient dose escalation):&#xD;
Grade 3 or greater non-hematologic toxicity with the exception of Grade 3 infusion reaction.&#xD;
Grade 4 neutropenia lasting more than 5 days despite appropriate medical management.&#xD;
Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion.&#xD;
Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC).&#xD;
Grade 4 anemia unexplained by underlying disease.&#xD;
Any AE requiring a dose delay of greater than 14 days.&#xD;
Patients with baseline cytopenias or starting blood counts in the grade 2 range are evaluable for hematologic DLT.</description>
          <units>Occurrence of DLTs</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="3"/>
                <count group_id="O6" value="3"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs.</title>
        <description>Treatment emergent adverse events (description, timing, CTCAE grade, severity, seriousness, and relatedness)</description>
        <time_frame>From the start of investigational treatment to completion of follow-up, an average of 33 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cirmtuzumab 0.015 - 0.03 mg/kg</title>
            <description>Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</title>
            <description>Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O3">
            <title>Cirmtuzumab 0.5 - 1.0 mg/kg</title>
            <description>Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O4">
            <title>Cirmtuzumab 2.0 - 4.0 mg/kg</title>
            <description>Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O5">
            <title>Cirmtuzumab 8 mg/kg</title>
            <description>Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O6">
            <title>Cirmtuzumab 16 mg/kg</title>
            <description>Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
          </group>
          <group group_id="O7">
            <title>Cirmtuzumab 20 mg/kg</title>
            <description>Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs.</title>
          <description>Treatment emergent adverse events (description, timing, CTCAE grade, severity, seriousness, and relatedness)</description>
          <units>Treatment emergent AEs</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="3"/>
                <count group_id="O6" value="3"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="37"/>
                    <measurement group_id="O3" value="15"/>
                    <measurement group_id="O4" value="31"/>
                    <measurement group_id="O5" value="17"/>
                    <measurement group_id="O6" value="34"/>
                    <measurement group_id="O7" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria</title>
        <description>Clinical response [stable disease (SD) or progressive disease (PD)] defined by iwCLL criteria including clinical, hematological, and bone marrow features for a period of at least 2 months from completion of therapy</description>
        <time_frame>From baseline visit to response assessment visit at 56 days after final cirmtuzumab infusion, an average of 52 days</time_frame>
        <population>Evaluable subjects or those who completed 4 cycles of cirmtuzumab</population>
        <group_list>
          <group group_id="O1">
            <title>Cirmtuzumab 0.015 - 0.03 mg/kg</title>
            <description>Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</title>
            <description>Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O3">
            <title>Cirmtuzumab 0.5 - 1.0 mg/kg</title>
            <description>Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O4">
            <title>Cirmtuzumab 2.0 - 4.0 mg/kg</title>
            <description>Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O5">
            <title>Cirmtuzumab 8 mg/kg</title>
            <description>Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O6">
            <title>Cirmtuzumab 16 mg/kg</title>
            <description>Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
          </group>
          <group group_id="O7">
            <title>Cirmtuzumab 20 mg/kg</title>
            <description>Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria</title>
          <description>Clinical response [stable disease (SD) or progressive disease (PD)] defined by iwCLL criteria including clinical, hematological, and bone marrow features for a period of at least 2 months from completion of therapy</description>
          <population>Evaluable subjects or those who completed 4 cycles of cirmtuzumab</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="2"/>
                <count group_id="O6" value="3"/>
                <count group_id="O7" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="1"/>
                    <measurement group_id="O7" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="2"/>
                    <measurement group_id="O7" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival as Determined by iwCLL Criteria</title>
        <description>The duration of time from the start of study treatment until objective tumor progression or death</description>
        <time_frame>From start of treatment until objective tumor progression or death</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cirmtuzumab 0.015 - 0.03 mg/kg</title>
            <description>Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion</description>
          </group>
          <group group_id="O2">
            <title>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</title>
            <description>Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O3">
            <title>Cirmtuzumab 0.5 - 1.0 mg/kg</title>
            <description>Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O4">
            <title>Cirmtuzumab 2.0 - 4.0 mg/kg</title>
            <description>Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O5">
            <title>Cirmtuzumab 8 mg/kg</title>
            <description>Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion</description>
          </group>
          <group group_id="O6">
            <title>Cirmtuzumab 16 mg/kg</title>
            <description>Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
          </group>
          <group group_id="O7">
            <title>Cirmtuzumab 20 mg/kg</title>
            <description>Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival as Determined by iwCLL Criteria</title>
          <description>The duration of time from the start of study treatment until objective tumor progression or death</description>
          <units>Weeks</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="3"/>
                <count group_id="O6" value="3"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.5" lower_limit="2.0" upper_limit="79.9"/>
                    <measurement group_id="O2" value="27.6" lower_limit="10.5" upper_limit="54.2"/>
                    <measurement group_id="O3" value="24.5" lower_limit="18.5" upper_limit="32"/>
                    <measurement group_id="O4" value="36.6" lower_limit="1" upper_limit="136"/>
                    <measurement group_id="O5" value="25.4" lower_limit="4" upper_limit="42.2"/>
                    <measurement group_id="O6" value="26.2" lower_limit="20.5" upper_limit="29"/>
                    <measurement group_id="O7" value="19.9" lower_limit="5.2" upper_limit="56.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events collected from the start of the first infusion of cirmtuzumab to the last subject's final visit in long-term follow-up (on average 3 years 8 months)</time_frame>
      <desc>Note that some patients elected to enroll in extension study (ClinicalTrails.gov record #NCT02860676) and therefor the cut-off date for some may be the date patient was first treated on extension protocol. Timeframe for this result therefore difficult to reconcile as asked to report here.&#xD;
Note no deaths observed during the timeframe of the study observation period.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cirmtuzumab 0.015 - 0.03 mg/kg</title>
          <description>Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion</description>
        </group>
        <group group_id="E2">
          <title>Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg</title>
          <description>Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion</description>
        </group>
        <group group_id="E3">
          <title>Cirmtuzumab 0.5 - 1.0 mg/kg</title>
          <description>Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion</description>
        </group>
        <group group_id="E4">
          <title>Cimrtuzumab 2.0 - 4.0 mg/kg</title>
          <description>Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion</description>
        </group>
        <group group_id="E5">
          <title>Cirmtuzumab 8 mg/kg</title>
          <description>Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion</description>
        </group>
        <group group_id="E6">
          <title>Cirmtuzumab 16 mg/kg</title>
          <description>Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion</description>
        </group>
        <group group_id="E7">
          <title>Cirmtuzumab 20 mg/kg</title>
          <description>Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)</description>
        </group>
      </group_list>
      <serious_events>
        <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="4"/>
                <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="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Grade 2, assessed as not related to investigational drug</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <description>Grade 3, assessed as unlikely related to investigational drug</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin infection</sub_title>
                <description>Grade 3, assessed as unlikely related to investigational drug</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="4" subjects_at_risk="4"/>
                <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="5" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="6"/>
              </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="6" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E2" events="12" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="9" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="9" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E6" events="14" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E7" events="10" subjects_affected="4" subjects_at_risk="6"/>
              </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="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders - other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>External ear pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye disorders - other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Floater</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fecal incontinence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastrointestinal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <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="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Flu-like symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="6" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E2" events="9" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="8" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E5" events="5" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E6" events="7" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E7" events="11" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E6" events="10" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E7" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </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="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="3" 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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="3" 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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Parasthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Transient ischemic attacks</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urine discoloration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </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="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin induration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <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="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <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="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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>
    <limitations_and_caveats>Some patients enrolled in extension study (#NCT02860676)&amp; cut-off date for AE observation may be date patient was first treated on extension, therefor AE Timeframe period difficult to reconcile. 0 deaths observed during study observation period.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Thomas Kipps, MD, PhD</name_or_title>
      <organization>University of California, San Diego</organization>
      <phone>858-534-5400</phone>
      <email>tkipps@ucsd.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/NCT02222688
org study id: #140141
nct id: NCT02222688
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the study is to investigate the safety of the investigational agent,
      cirmtuzumab. Cirmtuzumab is a monoclonal antibody drug designed to attach to a protein,
      called ROR1, on the surface of chronic lymphocytic leukemia (CLL) cells to block cell growth
      and survival. ROR1 is rarely expressed on healthy cells so the idea is to preferentially get
      rid of the cancer cells. Although there is evidence in laboratory animals that cirmtuzumab
      can decrease the number of CLL cells, the investigators do not know if this will work in
      humans. This drug will be given to humans for the first time in this study. Therefore, the
      goal of this study is to see if cirmtuzumab is safe and tolerated in study participants.
This is a first in human, open-label single institution, Phase I dose escalation study of in
      patients with relapsed or refractory CLL. Treatment cycle (14 days) will consist of
      cirmtuzumab administered intravenously on a bi-weekly (every two weeks) schedule for a total
      of 4 doses. Eight dose cohorts (of 3 to 6 patients in size) plus an expansion cohort of 6
      patients are planned. In the first 4 dose cohorts, there is intra-patient dose escalation to
      monitor for acute toxicities, such as tumor lysis syndrome.

      A cycle may be repeated every 14 days if the patient has at least stable disease by clinical
      examination (or interim response assessment) and has again met hematologic, renal, and
      hepatic laboratory parameters as defined in the eligibility section, and is without ongoing
      Grade 3 non-hematologic or Grade 4 hematologic toxicities attributable to cirmtuzumab. The
      total duration of study drug administration is 4 cycles. Each cycle consists of clinical and
      laboratory evaluation on Day 1 and safety assessments on Days 3 and 8.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab
time frame: 1 year
description: The MTD is defined as the highest dose studied at which no more than one in six patients experience a dose-limiting toxicity (DLT) during the DLT observation period. The biologically active dose will be determined at a dose below or equal to the MTD upon review of the the study data; the final determination will also consider any cumulative or delayed toxicity.
measure: Rate of Dose Limiting Toxicities (DLTs)
time frame: The DLT observation period is 56 days from the start of the first infusion for the intra-patient dosing cohorts and 28 days after the start of the first infusion for subsequent dosing cohorts
description: The occurrence of any of the following adverse events considered to be possibly, probably, or definitely related to cirmtuzumab within the DLT observation period (56 days from the first infusion for cohorts with intrapatient dose escalation, and 28 days of the start investigational treatment for cohorts without intrapatient dose escalation):
Grade 3 or greater non-hematologic toxicity with the exception of Grade 3 infusion reaction.
Grade 4 neutropenia lasting more than 5 days despite appropriate medical management.
Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion.
Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC).
Grade 4 anemia unexplained by underlying disease.
Any AE requiring a dose delay of greater than 14 days.
Patients with baseline cytopenias or starting blood counts in the grade 2 range are evaluable for hematologic DLT.
measure: Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs.
time frame: From the start of investigational treatment to completion of follow-up, an average of 33 weeks
description: Treatment emergent adverse events (description, timing, CTCAE grade, severity, seriousness, and relatedness)
measure: Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria
time frame: From baseline visit to response assessment visit at 56 days after final cirmtuzumab infusion, an average of 52 days
description: Clinical response [stable disease (SD) or progressive disease (PD)] defined by iwCLL criteria including clinical, hematological, and bone marrow features for a period of at least 2 months from completion of therapy
measure: Progression Free Survival as Determined by iwCLL Criteria
time frame: From start of treatment until objective tumor progression or death
description: The duration of time from the start of study treatment until objective tumor progression or death
arm group label: Cirmtuzumab 0.015 - 0.03 mg/kg
arm group type: Experimental
description: Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion
arm group label: Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg
arm group type: Experimental
description: Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion
arm group label: Cirmtuzumab 0.5 - 1.0 mg/kg
arm group type: Experimental
description: Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion
arm group label: Cirmtuzumab 2.0 - 4.0 mg/kg
arm group type: Experimental
description: Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion
arm group label: Cirmtuzumab 8 mg/kg
arm group type: Experimental
description: Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion
arm group label: Cirmtuzumab 16 mg/kg
arm group type: Experimental
description: Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion
arm group label: Cirmtuzumab 20 mg/kg
arm group type: Experimental
description: Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)
intervention type: Drug
intervention name: cirmtuzumab
arm group label: Cirmtuzumab 0.015 - 0.03 mg/kg
arm group label: Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg
arm group label: Cirmtuzumab 0.5 - 1.0 mg/kg
arm group label: Cirmtuzumab 16 mg/kg
arm group label: Cirmtuzumab 2.0 - 4.0 mg/kg
arm group label: Cirmtuzumab 20 mg/kg
arm group label: Cirmtuzumab 8 mg/kg
other name: UC-961
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Catriona Jamieson, M.D., Ph.D.
role: Principal Investigator
affiliation: University of California Medical Center
last name: Michael Choi, M.D.
role: Principal Investigator
affiliation: University of Calilfornia Medical Center
facility: 
country: United States
citation: Choi MY, Widhopf GF 2nd, Ghia EM, Kidwell RL, Hasan MK, Yu J, Rassenti LZ, Chen L, Chen Y, Pittman E, Pu M, Messer K, Prussak CE, Castro JE, Jamieson C, Kipps TJ. Phase I Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia. Cell Stem Cell. 2018 Jun 1;22(6):951-959.e3. doi: 10.1016/j.stem.2018.05.018.
PMID: 29859176
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Diego
investigator full name: Thomas Kipps
investigator title: Deputy Director of Research Operations, Moores Cancer Center
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Some patients enrolled in extension study (#NCT02860676)& cut-off date for AE observation may be date patient was first treated on extension, therefor AE Timeframe period difficult to reconcile. 0 deaths observed during study observation period.
point of contact: 