<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/NCT02264574</url>
  </required_header>
  <id_info>
    <org_study_id>PCYC-1130-CA</org_study_id>
    <nct_id>NCT02264574</nct_id>
  </id_info>
  <brief_title>A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment naïve Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)</brief_title>
  <official_title>A Randomized, Multi-center, Open-label, Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pharmacyclics LLC.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pharmacyclics LLC.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the efficacy of ibrutinib in combination&#xD;
      with obinutuzumab compared to chlorambucil in combination with obinutuzumab based on the&#xD;
      Independent Review Committee (IRC) assessment of progression free survival (PFS). Efficacy&#xD;
      will be evaluated according to 2008 International Workshop for Chronic Lymphocytic Leukemia&#xD;
      (IWCLL) criteria with the modification for treatment-related lymphocytosis, in subjects with&#xD;
      treatment-naive CLL or SLL.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 6, 2014</start_date>
  <completion_date type="Actual">September 3, 2019</completion_date>
  <primary_completion_date type="Actual">March 26, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Analysis: Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 30</measure>
    <time_frame>Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).</time_frame>
    <description>PFS was defined as time from the date randomization to the date of first IRC-confirmed disease progression (PD) or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.&#xD;
The primary analysis was performed after observing 94 PFS events as pre-specified in the study protocol. As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Final Analysis: PFS Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48</measure>
    <time_frame>Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).</time_frame>
    <description>PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Primary Analysis: PFS in High-Risk Sub-Population (del17p/TP53 Mutation/Del 11q) Based on IRC Assessment - Kaplan Meier Landmark Estimates at Month 30</measure>
    <time_frame>Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).</time_frame>
    <description>PFS was analyzed within the high-risk sub-population of participants with del17p or TP53 mutation or del 11q at baseline per central lab results. PFS was defined as time from the date randomization to the date of first IRC-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary Analysis: Rate of Sustained Hemoglobin Improvement</measure>
    <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
    <description>Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response</measure>
    <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
    <description>Percentage of participants who achieved MRD-negative response, defined as &lt; 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary Analysis: Overall Response Rate (ORR) Based on IRC Assessment</measure>
    <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
    <description>ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), or partial response (PR) per IRC assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 30</measure>
    <time_frame>Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).</time_frame>
    <description>OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.&#xD;
As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier landmark estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 30 [primary analysis]) are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary Analysis: Rate of Grade ≥ 3 or Serious Infusion-Related Reaction (IRR) Adverse Events</measure>
    <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
    <description>Percentage of participants experiencing grade ≥ 3 (severe or life threatening) or serious IRR adverse events that started on the day of an obinutuzumab infusion and were assessed as related or possibly related to obinutuzumab. Categories included those events with the Medical Dictionary for Regulatory Activities (MedDRA) dictionary preferred term of IRR and those events which are among the customized standardized MedDRA query (SMQ) for IRR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary Analysis: Rate of Sustained Platelet Improvement</measure>
    <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
    <description>Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary Analysis: Rate of Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EuroQol Five-Dimension (EQ-5D-5L)</measure>
    <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
    <description>Percentage of participants with EQ-5D-5L utility score increase ≥ 0.08 points over baseline at or prior to initiation of subsequent antineoplastic therapy. The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life, comprising 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the participant's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. Participants with missing EQ-5D-5L data were considered not achieving clinically meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Final Analysis: PFS in High-Risk Population (del17p/TP53 Mutation/Del 11q/Unmutated Immunoglobulin Heavy Chain Variable Region [IGHV]) Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48</measure>
    <time_frame>Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).</time_frame>
    <description>PFS was analyzed within the high-risk population of participants with del17p or TP53 mutation or del 11q or IGHV unmutated at baseline per central lab results. PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Final Analysis: Rate of Sustained Hemoglobin Improvement</measure>
    <time_frame>Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).</time_frame>
    <description>Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Final Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response</measure>
    <time_frame>Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).</time_frame>
    <description>Percentage of participants who achieved MRD-negative response, defined as &lt; 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Final Analysis: ORR Based on Investigator Assessment</measure>
    <time_frame>Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).</time_frame>
    <description>ORR, defined as the percentage of participants achieving a best overall response of protocol-specified CR, CRi, nPR or PR per investigator assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Final Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 48</measure>
    <time_frame>Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).</time_frame>
    <description>OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.&#xD;
As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 48 [final analysis]) are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Final Analysis: Rate of Sustained Platelet Improvement</measure>
    <time_frame>Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).</time_frame>
    <description>Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">229</enrollment>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small-Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>IBR + OB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity. Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CLB + OB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibrutinib</intervention_name>
    <description>Ibrutinib will be supplied as 140 mg hard gelatin capsules for oral (PO) administration.</description>
    <arm_group_label>IBR + OB</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Obinutuzumab</intervention_name>
    <description>Obinutuzumab will be supplied as 1000 mg/40 mL solution in a single-use vial for intravenous (IV) administration</description>
    <arm_group_label>CLB + OB</arm_group_label>
    <arm_group_label>IBR + OB</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chlorambucil</intervention_name>
    <description>Chlorambucil will be supplied as 2 mg film-coated tablets for oral (PO) administration</description>
    <arm_group_label>CLB + OB</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Disease Related:&#xD;
&#xD;
          1. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.&#xD;
&#xD;
          2. Age 65 yrs and older OR if less than 65 years, must have at least one of the following&#xD;
             criteria:&#xD;
&#xD;
               -  Cumulative Illness Rating Score (CIRS) &gt;6&#xD;
&#xD;
               -  Creatinine clearance estimated &lt;70 mL/min using Cockcroft-Gault equation.&#xD;
&#xD;
               -  Del 17p by fluorescence in situ hybridization (FISH) or TP53 mutation by&#xD;
                  polymerase chain reaction (PCR) or Next Generation Sequencing&#xD;
&#xD;
          3. Active disease meeting at least 1 of the following IWCLL criteria for requiring&#xD;
             treatment:&#xD;
&#xD;
               -  Evidence of progressive marrow failure as manifested by the development of, or&#xD;
                  worsening of, anemia and thrombocytopenia&#xD;
&#xD;
               -  Massive, progressive, or symptomatic splenomegaly&#xD;
&#xD;
               -  Massive nodes (at least 10 cm longest diameter), or progressive or symptomatic&#xD;
                  lymphadenopathy.&#xD;
&#xD;
               -  Progressive lymphocytosis with an increase of more than 50 percent over a 2-month&#xD;
                  period or a lymphocyte doubling time (LDT) of &lt;6 months. LDT may be obtained by&#xD;
                  linear regression extrapolation of absolute lymphocyte counts obtained at&#xD;
                  intervals of 2 weeks over an observation period of 2 to 3 months. In patients&#xD;
                  with initial blood lymphocyte counts of &lt;30,000/µL, LDT should not be used as a&#xD;
                  single parameter to define indication for treatment. In addition, factors&#xD;
                  contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections)&#xD;
                  should be excluded.&#xD;
&#xD;
               -  Autoimmune hemolytic anemia and/or immune thrombocytopenia that is poorly&#xD;
                  responsive to corticosteroids or other standard therapy.&#xD;
&#xD;
               -  Autoimmune hemolytic anemia is defined by at least one marker of hemolysis&#xD;
                  (indirect bilirubin above the upper limit of normal (ULN) not due to liver&#xD;
                  disease, increased lactate dehydrogenase (above ULN) without alternative&#xD;
                  etiology, or increased absolute reticulocytosis (above ULN) or bone marrow&#xD;
                  erythropoiesis in the absence of bleeding AND at least one marker direct or&#xD;
                  indirect autoimmune mechanism (positive direct antiglobulin for immunoglobulin G&#xD;
                  [IgG] or C3d, cold agglutinins).&#xD;
&#xD;
               -  Immune thrombocytopenia is defined by platelets ≤100,000/µL and increased&#xD;
                  megakaryocytes on the bone marrow exam.&#xD;
&#xD;
               -  Constitutional symptoms, defined as one or more of the following disease-related&#xD;
                  symptoms or signs, documented in the patient's record prior to randomization:&#xD;
&#xD;
               -  unintentional weight loss &gt;10 percent within 6 months prior to screening.&#xD;
&#xD;
               -  significant fatigue (inability to work or perform usual activities).&#xD;
&#xD;
               -  fevers &gt;100.5°F or 38.0°C for 2 or more weeks prior to screening without evidence&#xD;
                  of infection.&#xD;
&#xD;
               -  night sweats for more than 1 month prior to screening without evidence of&#xD;
                  infection.&#xD;
&#xD;
          4. Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node&#xD;
             &gt;1.5 cm in the longest diameter in a site that has not been previously irradiated. An&#xD;
             irradiated lesion may be assessed for measurable disease only if there has been&#xD;
             documented progression in that lesion since radiotherapy has ended.&#xD;
&#xD;
             Laboratory&#xD;
&#xD;
          5. Adequate hematologic function independent of transfusion and growth factor support for&#xD;
             at least 7 days prior to screening and randomization.&#xD;
&#xD;
          6. Adequate hepatic and renal function&#xD;
&#xD;
          7. Men and women ≥ 18 years of age.&#xD;
&#xD;
          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any prior treatment of CLL or SLL&#xD;
&#xD;
          2. Evidence of central nervous system (CNS) involvement with primary disease of CLL/SLL&#xD;
&#xD;
          3. History of other malignancies, except:&#xD;
&#xD;
               -  Malignancy treated with curative intent and with no known active disease present&#xD;
                  for ≥3 years before the first dose of study drug and felt to be at low risk for&#xD;
                  recurrence by treating physician.&#xD;
&#xD;
          4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura&#xD;
&#xD;
          5. Known or suspected history of Richter's transformation.&#xD;
&#xD;
          6. Concurrent administration of &gt;20mg/day of prednisone within 7 days of randomization&#xD;
             unless indicated for prophylaxis or management of allergic reactions (eg, contrast)&#xD;
&#xD;
          7. Known hypersensitivity to one or more study drugs&#xD;
&#xD;
          8. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.&#xD;
&#xD;
          9. Any uncontrolled active systemic infection or an infection requiring systemic&#xD;
             treatment that was completed ≤ 7 days before randomization.&#xD;
&#xD;
         10. Known bleeding disorders or hemophilia.&#xD;
&#xD;
         11. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.&#xD;
&#xD;
         12. Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus&#xD;
             (HBV) or hepatitis C virus (HCV).&#xD;
&#xD;
         13. Major surgery within 4 weeks of randomization.&#xD;
&#xD;
         14. Any life-threatening illness, medical condition, or organ system dysfunction that, in&#xD;
             the investigator's opinion, could compromise the subject's safety or put the study&#xD;
             outcomes at undue risk.&#xD;
&#xD;
         15. Currently active, clinically significant cardiovascular disease, such as uncontrolled&#xD;
             arrhythmia or Class 3 or 4 congestive heart failure or a history of myocardial&#xD;
             infarction, unstable angina, or acute coronary syndrome within 6 months prior to&#xD;
             randomization.&#xD;
&#xD;
         16. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting&#xD;
             gastrointestinal function, or resection of the stomach or small bowel, symptomatic&#xD;
             inflammatory bowel disease or ulcerative colitis, or partial or complete bowel&#xD;
             obstruction.&#xD;
&#xD;
         17. Concomitant use of warfarin or other vitamin K antagonists.&#xD;
&#xD;
         18. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.&#xD;
&#xD;
         19. Lactating or pregnant&#xD;
&#xD;
         20. Unwilling or unable to participate in all required study evaluations and procedures.&#xD;
&#xD;
         21. Unable to understand the purpose and risks of the study and to provide a signed and&#xD;
             dated informed consent form (ICF) and authorization to use protected health&#xD;
             information (in accordance with national and local subject privacy regulations).&#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>Lori Styles</last_name>
    <role>Study Director</role>
    <affiliation>Pharmacyclics LLC.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0241</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0844</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0763</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 071</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0712</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0845</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0868</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0123</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator #0503</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0650</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0888</name>
      <address>
        <city>Ballarat</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0193</name>
      <address>
        <city>Box Hill</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0633</name>
      <address>
        <city>Fitzroy</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0170</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0352</name>
      <address>
        <city>Linz</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0869</name>
      <address>
        <city>Salzburg</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0559</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0850</name>
      <address>
        <city>Turnhout</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 018</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0564</name>
      <address>
        <city>Hradec Kralove</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0854</name>
      <address>
        <city>Praha 10</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0769</name>
      <address>
        <city>Pessac cedex</city>
        <state>Gironde</state>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0520</name>
      <address>
        <city>Nantes cedex 1</city>
        <state>Loire Atlantique</state>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0775</name>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <state>Meurthe Et Moselle</state>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0855</name>
      <address>
        <city>Bayonne</city>
        <state>Pyrenees Atlantiques</state>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0573</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0577</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0579</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0575</name>
      <address>
        <city>Petach Tikva</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0856</name>
      <address>
        <city>Tel Aviv</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0875</name>
      <address>
        <city>Zerifin</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0860</name>
      <address>
        <city>Firenze</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0523</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0581</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0584</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0524</name>
      <address>
        <city>Modena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0582</name>
      <address>
        <city>Novara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0732</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0859</name>
      <address>
        <city>Siena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0663</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 662</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0586</name>
      <address>
        <city>Hamilton</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0592</name>
      <address>
        <city>Brzozow</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0531</name>
      <address>
        <city>Lodz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0708</name>
      <address>
        <city>Nizhniy Novgorod</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0707</name>
      <address>
        <city>Ryazan</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0881</name>
      <address>
        <city>Saint-Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 710</name>
      <address>
        <city>St. Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 304</name>
      <address>
        <city>Yaroslavl</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0604</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <state>Madrid</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0536</name>
      <address>
        <city>Majadahonda</city>
        <state>Madrid</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0533</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0534</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0535</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0537</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0864</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0874</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0790</name>
      <address>
        <city>Salamanca</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0870</name>
      <address>
        <city>Borås</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0865</name>
      <address>
        <city>Luleå</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0631</name>
      <address>
        <city>Lund</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0632</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0678</name>
      <address>
        <city>Istanbul</city>
        <state>Nisantasi</state>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0608</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 606</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0889</name>
      <address>
        <city>Denizli</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0601</name>
      <address>
        <city>Izmir</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0866</name>
      <address>
        <city>Samsun</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0867</name>
      <address>
        <city>Harlow</city>
        <state>Essex</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0365</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 0543</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <results_reference>
    <citation>Moreno C, Greil R, Demirkan F, Tedeschi A, Anz B, Larratt L, Simkovic M, Samoilova O, Novak J, Ben-Yehuda D, Strugov V, Gill D, Gribben JG, Hsu E, Lih CJ, Zhou C, Clow F, James DF, Styles L, Flinn IW. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Jan;20(1):43-56. doi: 10.1016/S1470-2045(18)30788-5. Epub 2018 Dec 3. Erratum In: Lancet Oncol. 2019 Jan;20(1):e10.</citation>
    <PMID>30522969</PMID>
  </results_reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <results_first_submitted>March 25, 2019</results_first_submitted>
  <results_first_submitted_qc>March 25, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">April 16, 2019</results_first_posted>
  <last_update_submitted>August 27, 2020</last_update_submitted>
  <last_update_submitted_qc>August 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obinutuzumab</mesh_term>
    <mesh_term>Chlorambucil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.</ipd_description>
    <ipd_url>http://yoda.yale.edu</ipd_url>
  </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>February 17, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT02264574/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>February 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT02264574/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted in 71 sites: 8 in the US, 36 in the EU, and 27 sites in 6 additional countries (Canada, Australia, New Zealand, Russia, Israel, Turkey). The first participant consented 06 October 2014. The last visit of the last participant was 03 September 2019, with a final database lock of 17 October 2019.</recruitment_details>
      <pre_assignment_details>Eligible participants were required to have had a diagnosis of active CLL/SLL conformant to IWCLL 2008 criteria. All subjects were required to have measurable nodal disease. Key exclusion criteria included any previous CLL/SLL treatment; known lymphoma or leukemia of the central nervous system, history/current evidence of Richter's transformation.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>IBR+OB</title>
          <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
        </group>
        <group group_id="P2">
          <title>CLB+OB</title>
          <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="113"/>
                <participants group_id="P2" count="116"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="84"/>
                <participants group_id="P2" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other, Not Specified</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>IBR+OB</title>
          <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
        </group>
        <group group_id="B2">
          <title>CLB+OB</title>
          <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="B3">
          <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="113"/>
            <count group_id="B2" value="116"/>
            <count group_id="B3" value="229"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                    <measurement group_id="B2" value="92"/>
                    <measurement group_id="B3" value="183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.0" lower_limit="47" upper_limit="87"/>
                    <measurement group_id="B2" value="72.0" lower_limit="40" upper_limit="86"/>
                    <measurement group_id="B3" value="71.0" lower_limit="40" upper_limit="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="79"/>
                    <measurement group_id="B3" value="146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="109"/>
                    <measurement group_id="B2" value="110"/>
                    <measurement group_id="B3" value="219"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="109"/>
                    <measurement group_id="B2" value="111"/>
                    <measurement group_id="B3" value="220"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Czechia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Russia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>New Zealand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Austria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sweden</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Turkey</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Belgium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Israel</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Primary Analysis: Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 30</title>
        <description>PFS was defined as time from the date randomization to the date of first IRC-confirmed disease progression (PD) or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.&#xD;
The primary analysis was performed after observing 94 PFS events as pre-specified in the study protocol. As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.</description>
        <time_frame>Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 30</title>
          <description>PFS was defined as time from the date randomization to the date of first IRC-confirmed disease progression (PD) or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.&#xD;
The primary analysis was performed after observing 94 PFS events as pre-specified in the study protocol. As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.</description>
          <population>Intent to Treat population: all randomized participants</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="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.5" lower_limit="69.5" upper_limit="85.2"/>
                    <measurement group_id="O2" value="31.1" lower_limit="22.5" upper_limit="40.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Log Rank</method>
            <method_desc>The treatment effect was tested with an unstratified log rank test.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.231</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.145</ci_lower_limit>
            <ci_upper_limit>0.367</ci_upper_limit>
            <estimate_desc>The hazard ratio and its 95% confidence interval were estimated using a Cox regression model with treatment as the only covariate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Analysis: PFS in High-Risk Sub-Population (del17p/TP53 Mutation/Del 11q) Based on IRC Assessment - Kaplan Meier Landmark Estimates at Month 30</title>
        <description>PFS was analyzed within the high-risk sub-population of participants with del17p or TP53 mutation or del 11q at baseline per central lab results. PFS was defined as time from the date randomization to the date of first IRC-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.</description>
        <time_frame>Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).</time_frame>
        <population>High-Risk Sub-Population Analysis Set: participants with del17p or TP53 mutation or del 11q at baseline per central lab results.</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: PFS in High-Risk Sub-Population (del17p/TP53 Mutation/Del 11q) Based on IRC Assessment - Kaplan Meier Landmark Estimates at Month 30</title>
          <description>PFS was analyzed within the high-risk sub-population of participants with del17p or TP53 mutation or del 11q at baseline per central lab results. PFS was defined as time from the date randomization to the date of first IRC-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.</description>
          <population>High-Risk Sub-Population Analysis Set: participants with del17p or TP53 mutation or del 11q at baseline per central lab results.</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="30"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.4" lower_limit="62.7" upper_limit="92.3"/>
                    <measurement group_id="O2" value="14.1" lower_limit="5.3" upper_limit="26.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Log Rank</method>
            <method_desc>The treatment effect was tested with an unstratified log rank test.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.119</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.046</ci_lower_limit>
            <ci_upper_limit>0.307</ci_upper_limit>
            <estimate_desc>The hazard ratio and its 95% confidence interval were estimated using a Cox regression model with treatment as the only covariate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Analysis: Rate of Sustained Hemoglobin Improvement</title>
        <description>Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.</description>
        <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: Rate of Sustained Hemoglobin Improvement</title>
          <description>Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.8"/>
                    <measurement group_id="O2" value="44.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5253</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response</title>
        <description>Percentage of participants who achieved MRD-negative response, defined as &lt; 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.</description>
        <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response</title>
          <description>Percentage of participants who achieved MRD-negative response, defined as &lt; 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.4"/>
                    <measurement group_id="O2" value="17.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5465</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Analysis: Overall Response Rate (ORR) Based on IRC Assessment</title>
        <description>ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), or partial response (PR) per IRC assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.</description>
        <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: Overall Response Rate (ORR) Based on IRC Assessment</title>
          <description>ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), or partial response (PR) per IRC assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.5"/>
                    <measurement group_id="O2" value="73.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0035</p_value>
            <method>Chi-squared</method>
            <param_type>Rate Ratio</param_type>
            <param_value>1.208</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.062</ci_lower_limit>
            <ci_upper_limit>1.373</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 30</title>
        <description>OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.&#xD;
As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier landmark estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 30 [primary analysis]) are presented.</description>
        <time_frame>Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 30</title>
          <description>OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.&#xD;
As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier landmark estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 30 [primary analysis]) are presented.</description>
          <population>Intent to Treat population: all randomized participants</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="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.5" lower_limit="77.4" upper_limit="90.9"/>
                    <measurement group_id="O2" value="84.9" lower_limit="76.8" upper_limit="90.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8057</p_value>
            <method>Log Rank</method>
            <method_desc>The treatment effect was tested with an unstratified log rank test.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.921</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.479</ci_lower_limit>
            <ci_upper_limit>1.772</ci_upper_limit>
            <estimate_desc>The hazard ratio and its 95% confidence interval were estimated using a Cox regression model with treatment as the only covariate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Analysis: Rate of Grade ≥ 3 or Serious Infusion-Related Reaction (IRR) Adverse Events</title>
        <description>Percentage of participants experiencing grade ≥ 3 (severe or life threatening) or serious IRR adverse events that started on the day of an obinutuzumab infusion and were assessed as related or possibly related to obinutuzumab. Categories included those events with the Medical Dictionary for Regulatory Activities (MedDRA) dictionary preferred term of IRR and those events which are among the customized standardized MedDRA query (SMQ) for IRR.</description>
        <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: Rate of Grade ≥ 3 or Serious Infusion-Related Reaction (IRR) Adverse Events</title>
          <description>Percentage of participants experiencing grade ≥ 3 (severe or life threatening) or serious IRR adverse events that started on the day of an obinutuzumab infusion and were assessed as related or possibly related to obinutuzumab. Categories included those events with the Medical Dictionary for Regulatory Activities (MedDRA) dictionary preferred term of IRR and those events which are among the customized standardized MedDRA query (SMQ) for IRR.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IRR (Preferred Term)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7"/>
                    <measurement group_id="O2" value="8.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>By Customized SMQ</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4"/>
                    <measurement group_id="O2" value="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>IRR Preferred Term&#xD;
To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0835</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>IRR By Customized SMQ&#xD;
To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1944</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Analysis: Rate of Sustained Platelet Improvement</title>
        <description>Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.</description>
        <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: Rate of Sustained Platelet Improvement</title>
          <description>Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.2"/>
                    <measurement group_id="O2" value="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0045</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Analysis: Rate of Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EuroQol Five-Dimension (EQ-5D-5L)</title>
        <description>Percentage of participants with EQ-5D-5L utility score increase ≥ 0.08 points over baseline at or prior to initiation of subsequent antineoplastic therapy. The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life, comprising 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the participant's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. Participants with missing EQ-5D-5L data were considered not achieving clinically meaningful improvement.</description>
        <time_frame>Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).</time_frame>
        <population>Intent to Treat population: all randomized participants with a baseline and post-baseline assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Analysis: Rate of Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EuroQol Five-Dimension (EQ-5D-5L)</title>
          <description>Percentage of participants with EQ-5D-5L utility score increase ≥ 0.08 points over baseline at or prior to initiation of subsequent antineoplastic therapy. The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life, comprising 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the participant's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. Participants with missing EQ-5D-5L data were considered not achieving clinically meaningful improvement.</description>
          <population>Intent to Treat population: all randomized participants with a baseline and post-baseline assessment.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="109"/>
                <count group_id="O2" value="107"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.9"/>
                    <measurement group_id="O2" value="56.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To preserve the study wise type I error rate of 0.05, the primary and secondary endpoints were tested based on serial gatekeeping testing procedure at the two-sided significance level of 0.05 according to the hierarchical order of the primary analysis outcome measures presented in this record.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8590</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Final Analysis: PFS in High-Risk Population (del17p/TP53 Mutation/Del 11q/Unmutated Immunoglobulin Heavy Chain Variable Region [IGHV]) Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48</title>
        <description>PFS was analyzed within the high-risk population of participants with del17p or TP53 mutation or del 11q or IGHV unmutated at baseline per central lab results. PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.</description>
        <time_frame>Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).</time_frame>
        <population>High-Risk Population Analysis Set: participants with del17p or TP53 mutation or del 11q or IGHV unmutated at baseline per central lab results.</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Final Analysis: PFS in High-Risk Population (del17p/TP53 Mutation/Del 11q/Unmutated Immunoglobulin Heavy Chain Variable Region [IGHV]) Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48</title>
          <description>PFS was analyzed within the high-risk population of participants with del17p or TP53 mutation or del 11q or IGHV unmutated at baseline per central lab results. PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.</description>
          <population>High-Risk Population Analysis Set: participants with del17p or TP53 mutation or del 11q or IGHV unmutated at baseline per central lab results.</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="73"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.3" lower_limit="57.6" upper_limit="79.8"/>
                    <measurement group_id="O2" value="8.0" lower_limit="2.3" upper_limit="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Log Rank</method>
            <method_desc>The treatment effect was tested with an unstratified log rank test.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.169</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.102</ci_lower_limit>
            <ci_upper_limit>0.282</ci_upper_limit>
            <estimate_desc>The hazard ratio and its 95% confidence interval were estimated using a Cox regression model with treatment as the only covariate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Final Analysis: Rate of Sustained Hemoglobin Improvement</title>
        <description>Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.</description>
        <time_frame>Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Final Analysis: Rate of Sustained Hemoglobin Improvement</title>
          <description>Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.2"/>
                    <measurement group_id="O2" value="44.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9657</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Final Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response</title>
        <description>Percentage of participants who achieved MRD-negative response, defined as &lt; 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.</description>
        <time_frame>Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Final Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response</title>
          <description>Percentage of participants who achieved MRD-negative response, defined as &lt; 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.8"/>
                    <measurement group_id="O2" value="17.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1612</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Final Analysis: ORR Based on Investigator Assessment</title>
        <description>ORR, defined as the percentage of participants achieving a best overall response of protocol-specified CR, CRi, nPR or PR per investigator assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.</description>
        <time_frame>Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Final Analysis: ORR Based on Investigator Assessment</title>
          <description>ORR, defined as the percentage of participants achieving a best overall response of protocol-specified CR, CRi, nPR or PR per investigator assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.2"/>
                    <measurement group_id="O2" value="81.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0273</p_value>
            <method>Chi-squared</method>
            <param_type>Rate Ratio</param_type>
            <param_value>1.125</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.013</ci_lower_limit>
            <ci_upper_limit>1.250</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Final Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 48</title>
        <description>OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.&#xD;
As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 48 [final analysis]) are presented.</description>
        <time_frame>Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Final Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 48</title>
          <description>OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.&#xD;
As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 48 [final analysis]) are presented.</description>
          <population>Intent to Treat population: all randomized participants</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="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.5" lower_limit="71.6" upper_limit="86.9"/>
                    <measurement group_id="O2" value="81.3" lower_limit="72.8" upper_limit="87.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7934</p_value>
            <method>Log Rank</method>
            <method_desc>The treatment effect was tested with an unstratified log rank test.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.083</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.595</ci_lower_limit>
            <ci_upper_limit>1.973</ci_upper_limit>
            <estimate_desc>The hazard ratio and its 95% confidence interval were estimated using a Cox regression model with treatment as the only covariate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Final Analysis: Rate of Sustained Platelet Improvement</title>
        <description>Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.</description>
        <time_frame>Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Final Analysis: Rate of Sustained Platelet Improvement</title>
          <description>Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.</description>
          <population>Intent to Treat population: all randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.1"/>
                    <measurement group_id="O2" value="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0050</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Final Analysis: PFS Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48</title>
        <description>PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.</description>
        <time_frame>Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).</time_frame>
        <population>Intent to Treat population: all randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IBR+OB</title>
            <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>CLB+OB</title>
            <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Final Analysis: PFS Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48</title>
          <description>PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.&#xD;
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.</description>
          <population>Intent to Treat population: all randomized participants</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="113"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.0" lower_limit="64.3" upper_limit="81.4"/>
                    <measurement group_id="O2" value="22.0" lower_limit="11.0" upper_limit="35.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Log Rank</method>
            <method_desc>The treatment effect was tested with an unstratified log rank test.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.251</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.162</ci_lower_limit>
            <ci_upper_limit>0.389</ci_upper_limit>
            <estimate_desc>The hazard ratio and its 95% confidence interval were estimated using a Cox regression model with treatment as the only covariate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug up to 30 days after the last dose of study drug. Median treatment duration for the IBR+OB arm was 42.3 (IBR) and 4.6 (OB) months. Median treatment duration for the CLB+OB arm was 5.1 (CLB) and 4.6 (OB) months. Final analysis data (data cutoff date: 17 October 2019).</time_frame>
      <desc>One participant in the CLB+OB arm was randomized but went off study without any treatment. This participant had received baseline assessments and was included in all efficacy analyses but was excluded from safety population, i.e. not at risk for adverse event assessment.</desc>
      <group_list>
        <group group_id="E1">
          <title>IBR+OB</title>
          <description>Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.</description>
        </group>
        <group group_id="E2">
          <title>CLB+OB</title>
          <description>Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.&#xD;
Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 22.0</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="22" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="69" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="115"/>
              </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="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Aplastic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Atrial tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pericarditis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pericarditis constrictive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Stress cardiomyopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Goitre</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Impaired gastric emptying</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Oesophageal rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Multi-organ disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Sudden Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Bacterial sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Bronchopulmonary aspergillosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Bursitis infective staphylococcal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Escherichia sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Escherichia urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Infective aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Listeria sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pneumocystis jirovecii pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pneumonia klebsiella</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Prostate infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Sinusitis fungal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Streptococcal bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Vascular device infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidental overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Incisional hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Jaw fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pubis fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Thoracic vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Traumatic haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Tumour lysis syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Compartment syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Inclusion body myositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Osteolysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Osteonecrosis of jaw</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adenocarcinoma gastric</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Adenocarcinoma of colon</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Benign renal neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Chronic lymphocytic leukaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Colorectal cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Colorectal cancer metastatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Essential thrombocythaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Invasive ductal breast carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Kaposi's sarcoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Keratoacanthoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Myelodysplastic syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Neuroendocrine carcinoma of the skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Non-small cell lung cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Osteoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Prostate Cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Acute psychosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Complete Suicide</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Uterine prolapse</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Bronchitis chronic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </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="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Venous thrombosis limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA Version 22.0</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="112" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="111" subjects_at_risk="115"/>
              </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="19" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Increased tendency to bruise</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="50" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="73" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Spontaneous haematoma</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="61" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="115"/>
              </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="11" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Iron deficiency</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </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="33" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </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="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Onychoclasis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="115"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="115"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="115"/>
              </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>Institution/Investigator will not publish without Sponsor prior review and approval&#xD;
Institution/Investigator will not publish until the earlier of (i) results of study are submitted for publication (ii) notification that submission of the multicenter results are no longer planned (iii) 18 months after study termination.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Lori Styles</name_or_title>
      <organization>Pharmacyclics LLC, An AbbVie Company</organization>
      <phone>(408) 215-3770</phone>
      <email>lstyles@pcyc.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/NCT02264574
org study id: PCYC-1130-CA
nct id: NCT02264574
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
The primary objective of this study is to evaluate the efficacy of ibrutinib in combination
      with obinutuzumab compared to chlorambucil in combination with obinutuzumab based on the
      Independent Review Committee (IRC) assessment of progression free survival (PFS). Efficacy
      will be evaluated according to 2008 International Workshop for Chronic Lymphocytic Leukemia
      (IWCLL) criteria with the modification for treatment-related lymphocytosis, in subjects with
      treatment-naive CLL or SLL.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Primary Analysis: Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 30
time frame: Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).
description: PFS was defined as time from the date randomization to the date of first IRC-confirmed disease progression (PD) or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.
The primary analysis was performed after observing 94 PFS events as pre-specified in the study protocol. As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.
measure: Final Analysis: PFS Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48
time frame: Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).
description: PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.
measure: Primary Analysis: PFS in High-Risk Sub-Population (del17p/TP53 Mutation/Del 11q) Based on IRC Assessment - Kaplan Meier Landmark Estimates at Month 30
time frame: Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).
description: PFS was analyzed within the high-risk sub-population of participants with del17p or TP53 mutation or del 11q at baseline per central lab results. PFS was defined as time from the date randomization to the date of first IRC-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.
measure: Primary Analysis: Rate of Sustained Hemoglobin Improvement
time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
description: Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.
measure: Primary Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response
time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
description: Percentage of participants who achieved MRD-negative response, defined as < 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.
measure: Primary Analysis: Overall Response Rate (ORR) Based on IRC Assessment
time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
description: ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), or partial response (PR) per IRC assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.
measure: Primary Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 30
time frame: Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).
description: OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.
As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier landmark estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 30 [primary analysis]) are presented.
measure: Primary Analysis: Rate of Grade ≥ 3 or Serious Infusion-Related Reaction (IRR) Adverse Events
time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
description: Percentage of participants experiencing grade ≥ 3 (severe or life threatening) or serious IRR adverse events that started on the day of an obinutuzumab infusion and were assessed as related or possibly related to obinutuzumab. Categories included those events with the Medical Dictionary for Regulatory Activities (MedDRA) dictionary preferred term of IRR and those events which are among the customized standardized MedDRA query (SMQ) for IRR.
measure: Primary Analysis: Rate of Sustained Platelet Improvement
time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
description: Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.
measure: Primary Analysis: Rate of Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EuroQol Five-Dimension (EQ-5D-5L)
time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
description: Percentage of participants with EQ-5D-5L utility score increase ≥ 0.08 points over baseline at or prior to initiation of subsequent antineoplastic therapy. The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life, comprising 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the participant's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. Participants with missing EQ-5D-5L data were considered not achieving clinically meaningful improvement.
measure: Final Analysis: PFS in High-Risk Population (del17p/TP53 Mutation/Del 11q/Unmutated Immunoglobulin Heavy Chain Variable Region [IGHV]) Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48
time frame: Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).
description: PFS was analyzed within the high-risk population of participants with del17p or TP53 mutation or del 11q or IGHV unmutated at baseline per central lab results. PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.
As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.
measure: Final Analysis: Rate of Sustained Hemoglobin Improvement
time frame: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).
description: Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.
measure: Final Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response
time frame: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).
description: Percentage of participants who achieved MRD-negative response, defined as < 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.
measure: Final Analysis: ORR Based on Investigator Assessment
time frame: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).
description: ORR, defined as the percentage of participants achieving a best overall response of protocol-specified CR, CRi, nPR or PR per investigator assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.
measure: Final Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 48
time frame: Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).
description: OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.
As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 48 [final analysis]) are presented.
measure: Final Analysis: Rate of Sustained Platelet Improvement
time frame: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).
description: Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.
arm group label: IBR + OB
arm group type: Experimental
description: Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity. Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.
arm group label: CLB + OB
arm group type: Experimental
description: Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.
Intravenous obinutuzumab given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Ibrutinib
description: Ibrutinib will be supplied as 140 mg hard gelatin capsules for oral (PO) administration.
arm group label: IBR + OB
intervention type: Drug
intervention name: Obinutuzumab
description: Obinutuzumab will be supplied as 1000 mg/40 mL solution in a single-use vial for intravenous (IV) administration
arm group label: CLB + OB
arm group label: IBR + OB
intervention type: Drug
intervention name: Chlorambucil
description: Chlorambucil will be supplied as 2 mg film-coated tablets for oral (PO) administration
arm group label: CLB + OB
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lori Styles
role: Study Director
affiliation: Pharmacyclics LLC.
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country: Australia
country: Austria
country: Belgium
country: Canada
country: Czechia
country: France
country: Israel
country: Italy
country: New Zealand
country: Poland
country: Russian Federation
country: Spain
country: Sweden
country: Turkey
country: United Kingdom
country: United States
country: Czech Republic
citation: Moreno C, Greil R, Demirkan F, Tedeschi A, Anz B, Larratt L, Simkovic M, Samoilova O, Novak J, Ben-Yehuda D, Strugov V, Gill D, Gribben JG, Hsu E, Lih CJ, Zhou C, Clow F, James DF, Styles L, Flinn IW. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Jan;20(1):43-56. doi: 10.1016/S1470-2045(18)30788-5. Epub 2018 Dec 3. Erratum In: Lancet Oncol. 2019 Jan;20(1):e10.
PMID: 30522969
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Obinutuzumab
mesh term: Chlorambucil
sharing ipd: Yes
ipd description: Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.
ipd url: http://yoda.yale.edu
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 