<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/NCT01693614</url>
  </required_header>
  <id_info>
    <org_study_id>CBKM120Z2402</org_study_id>
    <secondary_id>2012-002208-41</secondary_id>
    <nct_id>NCT01693614</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of BKM120 in Relapsed and Refractory NHL</brief_title>
  <official_title>An Open-label Phase II Study of BKM120 in Subjects With Relapsed and Refractory Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma and Follicular Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II study evaluating the safety, tolerability and efficacy of BKM120 in&#xD;
      patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell&#xD;
      lymphoma (MCL) or follicular lymphoma (FL).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 28, 2013</start_date>
  <completion_date type="Actual">July 21, 2017</completion_date>
  <primary_completion_date type="Actual">July 21, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS)</measure>
    <time_frame>Baseline up to 6 months</time_frame>
    <description>Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)</measure>
    <time_frame>Baseline up to approximately 44 months</time_frame>
    <description>Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)</measure>
    <time_frame>Baseline up to approximately 18 months</time_frame>
    <description>Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) - Percentage of Participants With OS Events (FAS)</measure>
    <time_frame>Baseline up to approximately 44 months</time_frame>
    <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)</measure>
    <time_frame>Baseline up to approximately 18 months</time_frame>
    <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival - Median (FAS)</measure>
    <time_frame>Baseline up approximately 44 months</time_frame>
    <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma</condition>
  <arm_group>
    <arm_group_label>DLBCL Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Diffuse large B-cell lymphoma cohort</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MCL Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mantle cell lymphoma cohort</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FL Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Follicular lymphoma cohort</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buparlisib</intervention_name>
    <description>100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days</description>
    <arm_group_label>DLBCL Cohort</arm_group_label>
    <arm_group_label>FL Cohort</arm_group_label>
    <arm_group_label>MCL Cohort</arm_group_label>
    <other_name>BKM120</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient had a histologically confirmed diagnosis of mantle cell lymphoma, follicular&#xD;
             lymphoma, or diffuse large B cell lymphoma.&#xD;
&#xD;
          2. Patient had relapsed or refractory disease and received at least one prior therapy.&#xD;
&#xD;
          3. Patient with diffuse large B cell lymphoma had received or was ineligible for&#xD;
             autologous or allogeneic stem cell transplant.&#xD;
&#xD;
          4. Patient had at least one measurable nodal lesion (≥2 cm) according to Cheson criteria&#xD;
             (Cheson 2007). In case where the patient had no measurable nodal lesions ≥ 2 cm in the&#xD;
             long axis at baseline, then the patient must have had at least one measurable&#xD;
             extra-nodal lesion.&#xD;
&#xD;
          5. Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.&#xD;
&#xD;
          6. Patient had adequate bone marrow and organ function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient had received previous treatment with PI3K inhibitors&#xD;
&#xD;
          2. Patient had evidence of graft versus host disease (GVHD).&#xD;
&#xD;
          3. Patient had active or history of central nervous system (CNS) disease.&#xD;
&#xD;
          4. Patient had a concurrent malignancy or had a malignancy within 3 years of study&#xD;
             enrollment (with the exception of adequately treated basal or squamous cell carcinoma&#xD;
             or non-melanomatous skin cancer).&#xD;
&#xD;
          5. Patient had a score ≥ 12 on the PHQ-9 questionnaire.&#xD;
&#xD;
          6. Patient had a GAD-7 mood scale score ≥ 15.&#xD;
&#xD;
          7. Pregnant or nursing women&#xD;
&#xD;
          8. Patient who did not use highly effective contraception methods to avoid becoming&#xD;
             pregnant or conceiving offspring.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center Univ Nebraska</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Dept of Onc.</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina -Hollings Cancer Center Medical Univ of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brugge</city>
        <zip>8000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Yvoir</city>
        <zip>5530</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Marseille</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pierre-Benite Cedex</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rennes</city>
        <zip>35019</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wurzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gyeonggi-do</city>
        <state>Korea</state>
        <zip>10408</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Salamanca</city>
        <state>Castilla Y Leon</state>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hospitalet de LLobregat</city>
        <state>Catalunya</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Izmir</city>
        <zip>35040</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Samsun</city>
        <zip>55139</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Brazil</country>
  </removed_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <results_first_submitted>July 19, 2018</results_first_submitted>
  <results_first_submitted_qc>August 30, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 28, 2018</results_first_posted>
  <last_update_submitted>August 30, 2018</last_update_submitted>
  <last_update_submitted_qc>August 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diffuse large B-cell lymphoma, Mantle cell lymphoma, Follicular lymphoma, PI3K inhibitor, Non-Hodgkin lymphoma, NHL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 9, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT01693614/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 16, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT01693614/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Primary reason for not completing is presented</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>DLBCL Cohort</title>
          <description>Diffuse large B-cell lymphoma cohort</description>
        </group>
        <group group_id="P2">
          <title>MCL Cohort</title>
          <description>Mantle cell lymphoma cohort</description>
        </group>
        <group group_id="P3">
          <title>FL Cohort</title>
          <description>Follicular lymphoma cohort</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="24"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by subject/guardian</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>DLBCL Cohort</title>
          <description>Diffuse large B-cell lymphoma cohort</description>
        </group>
        <group group_id="B2">
          <title>MCL Cohort</title>
          <description>Mantle cell lymphoma cohort</description>
        </group>
        <group group_id="B3">
          <title>FL Cohort</title>
          <description>Follicular lymphoma cohort</description>
        </group>
        <group group_id="B4">
          <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="26"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="24"/>
            <count group_id="B4" value="72"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.0" spread="14.57"/>
                    <measurement group_id="B2" value="67.9" spread="8.56"/>
                    <measurement group_id="B3" value="61.4" spread="13.11"/>
                    <measurement group_id="B4" value="62.9" spread="12.80"/>
                  </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="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <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="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS)</title>
        <description>Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR</description>
        <time_frame>Baseline up to 6 months</time_frame>
        <population>different numbers represents satisfying particular criteria</population>
        <group_list>
          <group group_id="O1">
            <title>DLBCL Cohort</title>
            <description>Diffuse large B-cell lymphoma cohort</description>
          </group>
          <group group_id="O2">
            <title>MCL Cohort</title>
            <description>Mantle cell lymphoma cohort</description>
          </group>
          <group group_id="O3">
            <title>FL Cohort</title>
            <description>Follicular lymphoma cohort</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS)</title>
          <description>Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR</description>
          <population>different numbers represents satisfying particular criteria</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="22"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ORR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5" lower_limit="2.45" upper_limit="30.15"/>
                    <measurement group_id="O2" value="22.7" lower_limit="7.82" upper_limit="45.37"/>
                    <measurement group_id="O3" value="25.0" lower_limit="9.77" upper_limit="46.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DCR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.8" lower_limit="14.33" upper_limit="51.79"/>
                    <measurement group_id="O2" value="81.8" lower_limit="59.72" upper_limit="94.81"/>
                    <measurement group_id="O3" value="87.5" lower_limit="67.64" upper_limit="97.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)</title>
        <description>Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort.</description>
        <time_frame>Baseline up to approximately 44 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>DLBCL Cohort</title>
            <description>Diffuse large B-cell lymphoma cohort</description>
          </group>
          <group group_id="O2">
            <title>MCL Cohort</title>
            <description>Mantle cell lymphoma cohort</description>
          </group>
          <group group_id="O3">
            <title>FL Cohort</title>
            <description>Follicular lymphoma cohort</description>
          </group>
        </group_list>
        <measure>
          <title>Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)</title>
          <description>Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="22"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" lower_limit="1.51" upper_limit="4.01"/>
                    <measurement group_id="O2" value="11.3" lower_limit="3.81" upper_limit="38.90"/>
                    <measurement group_id="O3" value="9.1" lower_limit="3.75" upper_limit="14.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)</title>
        <description>Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause</description>
        <time_frame>Baseline up to approximately 18 months</time_frame>
        <population>Number analyzed represents participants satisfying criteria for duration of response</population>
        <group_list>
          <group group_id="O1">
            <title>DLBCL Cohort</title>
            <description>Diffuse large B-cell lymphoma cohort</description>
          </group>
          <group group_id="O2">
            <title>FL Cohort</title>
            <description>Follicular lymphoma cohort</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)</title>
          <description>Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause</description>
          <population>Number analyzed represents participants satisfying criteria for duration of response</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" lower_limit="1.15" upper_limit="NA">Not able to estimate due to insufficient number of participants with events</measurement>
                    <measurement group_id="O2" value="11.0" lower_limit="3.94" upper_limit="NA">Not able to estimate due to insufficient number of participants with events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) - Percentage of Participants With OS Events (FAS)</title>
        <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit</description>
        <time_frame>Baseline up to approximately 44 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>DLBCL Cohort</title>
            <description>Diffuse large B-cell lymphoma cohort</description>
          </group>
          <group group_id="O2">
            <title>MCL Cohort</title>
            <description>Mantle cell lymphoma cohort</description>
          </group>
          <group group_id="O3">
            <title>FL Cohort</title>
            <description>Follicular lymphoma cohort</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) - Percentage of Participants With OS Events (FAS)</title>
          <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="22"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>OS events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0"/>
                    <measurement group_id="O2" value="22.7"/>
                    <measurement group_id="O3" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number censored</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0"/>
                    <measurement group_id="O2" value="77.3"/>
                    <measurement group_id="O3" value="91.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)</title>
        <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals</description>
        <time_frame>Baseline up to approximately 18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>DLBCL Cohort</title>
            <description>Diffuse large B-cell lymphoma cohort</description>
          </group>
          <group group_id="O2">
            <title>MCL Cohort</title>
            <description>Mantle cell lymphoma cohort</description>
          </group>
          <group group_id="O3">
            <title>FL Cohort</title>
            <description>Follicular lymphoma cohort</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)</title>
          <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="22"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.6" lower_limit="61.98" upper_limit="93.52"/>
                    <measurement group_id="O2" value="100.0" lower_limit="100.0" upper_limit="100.0"/>
                    <measurement group_id="O3" value="100.0" lower_limit="100.0" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.9" lower_limit="44.54" upper_limit="81.88"/>
                    <measurement group_id="O2" value="90.2" lower_limit="66.23" upper_limit="97.47"/>
                    <measurement group_id="O3" value="100.0" lower_limit="100.0" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.8" lower_limit="23.26" upper_limit="62.64"/>
                    <measurement group_id="O2" value="90.2" lower_limit="66.23" upper_limit="97.47"/>
                    <measurement group_id="O3" value="95.2" lower_limit="70.72" upper_limit="99.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.8" lower_limit="23.26" upper_limit="62.64"/>
                    <measurement group_id="O2" value="77.8" lower_limit="50.38" upper_limit="91.25"/>
                    <measurement group_id="O3" value="95.2" lower_limit="70.72" upper_limit="99.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.8" lower_limit="23.26" upper_limit="62.64"/>
                    <measurement group_id="O2" value="70.1" lower_limit="41.09" upper_limit="86.73"/>
                    <measurement group_id="O3" value="95.2" lower_limit="70.72" upper_limit="99.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival - Median (FAS)</title>
        <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals</description>
        <time_frame>Baseline up approximately 44 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>DLBCL Cohort</title>
            <description>Diffuse large B-cell lymphoma cohort</description>
          </group>
          <group group_id="O2">
            <title>MCL Cohort</title>
            <description>Mantle cell lymphoma cohort</description>
          </group>
          <group group_id="O3">
            <title>FL Cohort</title>
            <description>Follicular lymphoma cohort</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival - Median (FAS)</title>
          <description>Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="22"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" lower_limit="3.06" upper_limit="NA">Not able to estimate due to insufficient number of participants with events</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="15.64" upper_limit="NA">Not able to estimate due to insufficient number of participants with events</measurement>
                    <measurement group_id="O3" value="NA" lower_limit="22.74" upper_limit="NA">Not able to estimate due to insufficient number of participants with events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 18 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>DLBCL Cohort</title>
          <description>DLBCL</description>
        </group>
        <group group_id="E2">
          <title>MCL Cohort</title>
          <description>MCL</description>
        </group>
        <group group_id="E3">
          <title>FL Cohort</title>
          <description>FL</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (20.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anal fissure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Performance status decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Meningitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pneumonia streptococcal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Transitional cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebellar infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Essential tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Psychiatric decompensation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Lung infiltration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Toxic skin eruption</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (20.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="23" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatotoxicity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Jugular vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>Novartis.email@novartis.com</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/NCT01693614
org study id: CBKM120Z2402
secondary id: 2012-002208-41
nct id: NCT01693614
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a phase II study evaluating the safety, tolerability and efficacy of BKM120 in
      patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell
      lymphoma (MCL) or follicular lymphoma (FL).
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS)
time frame: Baseline up to 6 months
description: Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR
measure: Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)
time frame: Baseline up to approximately 44 months
description: Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort.
measure: Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)
time frame: Baseline up to approximately 18 months
description: Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause
measure: Overall Survival (OS) - Percentage of Participants With OS Events (FAS)
time frame: Baseline up to approximately 44 months
description: Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit
measure: Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)
time frame: Baseline up to approximately 18 months
description: Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals
measure: Overall Survival - Median (FAS)
time frame: Baseline up approximately 44 months
description: Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals
arm group label: DLBCL Cohort
arm group type: Experimental
description: Diffuse large B-cell lymphoma cohort
arm group label: MCL Cohort
arm group type: Experimental
description: Mantle cell lymphoma cohort
arm group label: FL Cohort
arm group type: Experimental
description: Follicular lymphoma cohort
intervention type: Drug
intervention name: Buparlisib
description: 100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days
arm group label: DLBCL Cohort
arm group label: FL Cohort
arm group label: MCL Cohort
other name: BKM120
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
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facility: 
country: Belgium
country: France
country: Germany
country: Italy
country: Korea, Republic of
country: Spain
country: Turkey
country: United States
country: Brazil
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 