<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/NCT02968563</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-401-1958</org_study_id>
    <secondary_id>2015-003909-42</secondary_id>
    <secondary_id>CLLRUmbrella1</secondary_id>
    <nct_id>NCT02968563</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib and Idelalisib With and Without Obinutuzumab in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)</brief_title>
  <official_title>A Prospective, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib (GS-4059) and Idelalisib With and Without Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German CLL Study Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine the preliminary efficacy of the&#xD;
      combination of tirabrutinib and idelalisib with obinutuzumab in adults with relapsed or&#xD;
      refractory chronic lymphocytic leukemia (CLL).&#xD;
&#xD;
      The study has a 6 participant per arm safety run-in to evaluate safety prior to the&#xD;
      enrollment of subsequent participants. The treatment period is adaptive, with a duration of&#xD;
      active treatment up to two years and a total follow-up on study for up to 30 days post end of&#xD;
      treatment, or up to Week 25 should a participant discontinue treatment prior to Week 25 for&#xD;
      reasons other than disease progression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 13, 2016</start_date>
  <completion_date type="Actual">January 14, 2021</completion_date>
  <primary_completion_date type="Actual">June 17, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of Complete Response/Complete Remission (CR), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25</measure>
    <time_frame>Week 25</time_frame>
    <description>Rate of CR per modified IWCLL 2008 criteria at Week 25 was defined as the percentage of participants who achieved CR/complete remission with incomplete recovery of the bone marrow (CRi) at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of CR With Bone Marrow Minimal Residual Disease (CR/BM MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</measure>
    <time_frame>Week 25</time_frame>
    <description>Rate of CR/BM MRD at Week 25 was defined as percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved BM MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with four-color-flow cytometry (FACS) and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,&lt;10^-4 and participants were defined as MRD negative if their disease burden was below this threshold.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of CR With Peripheral Minimal Residual Disease (CR/PB MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</measure>
    <time_frame>Week 25</time_frame>
    <description>Rate of CR/PB MRD at Week 25 was defined as the percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved PB MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with FACS and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,&lt;10^-4 and participants were defined as MRD negative if their disease burden was below this threshold.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</measure>
    <time_frame>Week 25</time_frame>
    <description>ORR was assessed based on modified IWCLL 2008 criteria and was defined as percentage of participants achieving a CR, CRi, partial remission (PR; including nodular partial response [nPR]), and PR with lymphocytosis (PR-L). CR and CRi: meeting all the criteria that have been defined in Outcome measures 1, 2 and 3. PR: ≥ 2 of these: ≥ 50% decrease in lymphocytes, lymphadenopathy, size of liver, size of spleen, and 50% decrease in bone marrow infiltrates; and ≥ 1 of these: neutrophils &gt; 1500/μL or ≥ 50% increase from Baseline, platelets ≥ 100,000/µL or ≥ 50% increase from Baseline, hemoglobin &gt;11 g/dL or ≥ 50% increase from Baseline. PR-L: meeting PR criteria; however, a lymphocytosis related to treatment may be present. nPR: All criteria for a CR/CRi were fulfilled, but the bone marrow showed lymphoid nodules.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)</measure>
    <time_frame>First dose date up to the last dose date (maximum: 105 weeks) plus 30 days</time_frame>
    <description>Treatment-emergent AEs are defined as 1 or both of the following:&#xD;
Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug&#xD;
Any AEs leading to discontinuation of study drug&#xD;
A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>Tirabrutinib + Idelalisib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tirabrutinib + Idelalisib + Obinutuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tirabrutinib</intervention_name>
    <description>Tablets administered orally</description>
    <arm_group_label>Tirabrutinib + Idelalisib</arm_group_label>
    <arm_group_label>Tirabrutinib + Idelalisib + Obinutuzumab</arm_group_label>
    <other_name>GS-4059</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Idelalisib</intervention_name>
    <description>Tablets administered orally</description>
    <arm_group_label>Tirabrutinib + Idelalisib</arm_group_label>
    <arm_group_label>Tirabrutinib + Idelalisib + Obinutuzumab</arm_group_label>
    <other_name>Zydelig®</other_name>
    <other_name>GS-1101</other_name>
    <other_name>CAL-101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Obinutuzumab</intervention_name>
    <description>Administered intravenously</description>
    <arm_group_label>Tirabrutinib + Idelalisib + Obinutuzumab</arm_group_label>
    <other_name>Gazyvaro®</other_name>
    <other_name>Gazyva®</other_name>
    <other_name>GA101</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Documentation of relapsed or refractory CLL&#xD;
&#xD;
          -  Requiring treatment per modified International Workshop on CLL (IWCLL) 2008 criteria;&#xD;
             individuals without radiographically measurable disease (defined as ≥ 1 lesion &gt; 1.5&#xD;
             centimetre (cm) in diameter as assessed by computed tomography (CT) or magnetic&#xD;
             resonance imaging [MRI]) must have bone marrow evaluation at screening&#xD;
&#xD;
          -  Adequate hematologic function: platelet count ≥ 50 × 10^9/L, neutrophil count ≥ 1 ×&#xD;
             10^9/L, hemoglobin ≥ 8 grams per decilitre (g/dL) unless lower values are directly&#xD;
             attributable to documented bone marrow burden of CLL&#xD;
&#xD;
          -  Creatinine clearance (CrCl) ≥ 50 milliliter per minute (mL/min)&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5× institutional upper limit of normal (ULN) unless attributed to&#xD;
             Gilbert's syndrome and aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 ×&#xD;
             ULN&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2&#xD;
&#xD;
          -  Absence of active human immunodeficiency virus (HIV), hepatitis B virus (HBV)&#xD;
             infection, hepatitis C virus (HCV) infection, and cytomegalovirus (CMV) infection&#xD;
&#xD;
          -  Satisfies the following criteria:&#xD;
&#xD;
               -  For females of childbearing potential, willingness to abstain from sexual&#xD;
                  intercourse or use a protocol-specified method of contraception as described in&#xD;
                  the study protocol&#xD;
&#xD;
               -  Males of reproductive potential who engage in sexual intercourse must agree to&#xD;
                  use protocol-specified method(s) of contraception as described in the study&#xD;
                  protocol&#xD;
&#xD;
          -  Able to comply with study procedures and restrictions including mandatory prophylaxis&#xD;
             for Pneumocystis jirovecii pneumonia (PJP)&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Known transformation of CLL (ie, Richter's transformation, prolymphocytic leukemia)&#xD;
&#xD;
          -  Known central nervous system (CNS) involvement&#xD;
&#xD;
          -  Progression on treatment with any inhibitor of Bruton's tyrosine kinase (BTK), spleen&#xD;
             tyrosine kinase (SYK), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2&#xD;
             (BCL-2), or obinutuzumab. The treatment and disease response history of individuals&#xD;
             with prior treatment with agents in these classes should be reviewed by the sponsor or&#xD;
             the German CLL Study Group (GCLLSG) study office prior to enrollment to clarify&#xD;
             sensitivity to these treatments.&#xD;
&#xD;
          -  Any treatment for CLL other than corticosteroids for symptomatic management within 28&#xD;
             days of the start of study treatment&#xD;
&#xD;
          -  Participation on a concurrent therapeutic clinical trial unless all treatment is&#xD;
             complete with only ongoing surveillance&#xD;
&#xD;
          -  Diagnosis of or concern for progressive multifocal leukoencephalopathy&#xD;
&#xD;
          -  History of myelodysplastic syndrome or another malignancy other than CLL, except for&#xD;
             the following: any malignancy that has been in complete remission for 3 years,&#xD;
             adequately treated local basal cell or squamous cell carcinoma of the skin, cervical&#xD;
             carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without&#xD;
             known metastatic disease and with no requirement for therapy or requiring only&#xD;
             hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to start&#xD;
             of study therapy&#xD;
&#xD;
          -  Active infection requiring systemic therapy&#xD;
&#xD;
          -  Pregnant or nursing women (a negative pregnancy test is required for all women of&#xD;
             childbearing potential within 7 days before start of treatment and monthly during&#xD;
             therapy)&#xD;
&#xD;
          -  Active autoimmune disease or the need for higher than prednisone 10 mg daily unless&#xD;
             for management of CLL symptoms&#xD;
&#xD;
          -  Treatment or prophylaxis for CMV within the past 28 days&#xD;
&#xD;
          -  History of stroke or intracranial hemorrhage within 12 months of randomization;&#xD;
             patients requiring therapeutic anticoagulation for any indication should be discussed&#xD;
             with the GCLLSG cooperating physician and/or medical monitor prior to screening.&#xD;
&#xD;
          -  Use of a strong CYP3A4 or a strong P-glycoprotein (P-gp) inducer within 2 weeks of&#xD;
             first dose of study treatment or anticipated chronic use while on study&#xD;
&#xD;
          -  Demonstration of corrected QT (QTc) interval &gt; 450 milliseconds or requirement for&#xD;
             ongoing treatment with concomitant medications that prolong the QT interval&#xD;
&#xD;
        Note: Other protocol defined Inclusion/Exclusion criteria may apply.&#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>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ambulante Krebszentrum Schaubstraße</name>
      <address>
        <city>Frankfurt</city>
        <state>Brandenburg</state>
        <zip>60596</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hämatologische-onkologische Gem.-Praxis Dres. Brudler-Heinrich-Bangerter, Augsburg</name>
      <address>
        <city>Augsburg</city>
        <zip>86150</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internistische Gemeinschaftspraxis Dres. Schliesser-Käbisch-Weber, Gießen</name>
      <address>
        <city>Gießen</city>
        <zip>35392</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinik Koln</name>
      <address>
        <city>Köln</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinik Leipzig</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Luebecker Onkologische Schwerpunktpraxis</name>
      <address>
        <city>Luebeck</city>
        <zip>23562</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitasmtedizin Mannheim</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stauferklinikum Schwäbisch Gmünd</name>
      <address>
        <city>Mutlangen</city>
        <zip>73557</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KH Maria Hilf-Franziskushaus, Mönchengladbach</name>
      <address>
        <city>Mönchengladbach</city>
        <zip>41063</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krankenhaus München-Schwabing</name>
      <address>
        <city>München</city>
        <zip>80804</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Rechts der Isar der Technischen Universität München</name>
      <address>
        <city>München</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Studienzentrum Onkologie Ravensburg</name>
      <address>
        <city>Ravensburg</city>
        <zip>88212</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Facharztzentrum Regensburg</name>
      <address>
        <city>Regensburg</city>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.dcllsg.de/studie/cllrUmbrella1/</url>
    <description>Click here for more information about this study: CLLRUmbrella1 (German CLL Study Group)</description>
  </link>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <results_first_submitted>June 12, 2020</results_first_submitted>
  <results_first_submitted_qc>June 12, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 1, 2020</results_first_posted>
  <last_update_submitted>December 24, 2021</last_update_submitted>
  <last_update_submitted_qc>December 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 21, 2022</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>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>Idelalisib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 28, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT02968563/Prot_002.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 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT02968563/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at study sites in Germany. The first participant was screened on 13 December 2016. The last study visit occurred on 14 January 2021.</recruitment_details>
      <pre_assignment_details>35 participants were screened. Randomization was discontinued after implementation of Protocol Amendment 3; all additional participants were enrolled to Arm: Tirabrutinib + Idelalisib + Obinutuzumab.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tirabrutinib + Idelalisib</title>
          <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Tirabrutinib + Idelalisib + Obinutuzumab</title>
          <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Full Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Tirabrutinib + Idelalisib</title>
          <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Tirabrutinib + Idelalisib + Obinutuzumab</title>
          <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.</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="5"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="35"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" spread="4.7"/>
                    <measurement group_id="B2" value="65" spread="9.4"/>
                    <measurement group_id="B3" value="65" spread="8.9"/>
                  </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="3"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Not Permitted = local regulators did not allow collection of race information.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Permitted</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Not Permitted = local regulators did not allow collection of ethnicity information.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ethnicity</title>
              <category_list>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Permitted</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Rate of Complete Response/Complete Remission (CR), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25</title>
        <description>Rate of CR per modified IWCLL 2008 criteria at Week 25 was defined as the percentage of participants who achieved CR/complete remission with incomplete recovery of the bone marrow (CRi) at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.</description>
        <time_frame>Week 25</time_frame>
        <population>The Full Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Tirabrutinib + Idelalisib</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tirabrutinib + Idelalisib + Obinutuzumab</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Complete Response/Complete Remission (CR), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25</title>
          <description>Rate of CR per modified IWCLL 2008 criteria at Week 25 was defined as the percentage of participants who achieved CR/complete remission with incomplete recovery of the bone marrow (CRi) at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.</description>
          <population>The Full Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="45.1"/>
                    <measurement group_id="O2" value="6.7" lower_limit="1.2" upper_limit="19.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of CR With Bone Marrow Minimal Residual Disease (CR/BM MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</title>
        <description>Rate of CR/BM MRD at Week 25 was defined as percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved BM MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with four-color-flow cytometry (FACS) and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,&lt;10^-4 and participants were defined as MRD negative if their disease burden was below this threshold.</description>
        <time_frame>Week 25</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tirabrutinib + Idelalisib</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tirabrutinib + Idelalisib + Obinutuzumab</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of CR With Bone Marrow Minimal Residual Disease (CR/BM MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</title>
          <description>Rate of CR/BM MRD at Week 25 was defined as percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved BM MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with four-color-flow cytometry (FACS) and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,&lt;10^-4 and participants were defined as MRD negative if their disease burden was below this threshold.</description>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="45.1"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of CR With Peripheral Minimal Residual Disease (CR/PB MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</title>
        <description>Rate of CR/PB MRD at Week 25 was defined as the percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved PB MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with FACS and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,&lt;10^-4 and participants were defined as MRD negative if their disease burden was below this threshold.</description>
        <time_frame>Week 25</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tirabrutinib + Idelalisib</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tirabrutinib + Idelalisib + Obinutuzumab</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of CR With Peripheral Minimal Residual Disease (CR/PB MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</title>
          <description>Rate of CR/PB MRD at Week 25 was defined as the percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved PB MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets &gt; 100,000/µL; hemoglobin &gt; 11 g/dL; and neutrophils &gt; 1500/µL. CRi: CR criteria (no lymphadenopathy &gt; 1.5 cm/hepatomegaly/splenomegaly; lymphocytes &lt; 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with FACS and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,&lt;10^-4 and participants were defined as MRD negative if their disease burden was below this threshold.</description>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="45.1"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</title>
        <description>ORR was assessed based on modified IWCLL 2008 criteria and was defined as percentage of participants achieving a CR, CRi, partial remission (PR; including nodular partial response [nPR]), and PR with lymphocytosis (PR-L). CR and CRi: meeting all the criteria that have been defined in Outcome measures 1, 2 and 3. PR: ≥ 2 of these: ≥ 50% decrease in lymphocytes, lymphadenopathy, size of liver, size of spleen, and 50% decrease in bone marrow infiltrates; and ≥ 1 of these: neutrophils &gt; 1500/μL or ≥ 50% increase from Baseline, platelets ≥ 100,000/µL or ≥ 50% increase from Baseline, hemoglobin &gt;11 g/dL or ≥ 50% increase from Baseline. PR-L: meeting PR criteria; however, a lymphocytosis related to treatment may be present. nPR: All criteria for a CR/CRi were fulfilled, but the bone marrow showed lymphoid nodules.</description>
        <time_frame>Week 25</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tirabrutinib + Idelalisib</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tirabrutinib + Idelalisib + Obinutuzumab</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25</title>
          <description>ORR was assessed based on modified IWCLL 2008 criteria and was defined as percentage of participants achieving a CR, CRi, partial remission (PR; including nodular partial response [nPR]), and PR with lymphocytosis (PR-L). CR and CRi: meeting all the criteria that have been defined in Outcome measures 1, 2 and 3. PR: ≥ 2 of these: ≥ 50% decrease in lymphocytes, lymphadenopathy, size of liver, size of spleen, and 50% decrease in bone marrow infiltrates; and ≥ 1 of these: neutrophils &gt; 1500/μL or ≥ 50% increase from Baseline, platelets ≥ 100,000/µL or ≥ 50% increase from Baseline, hemoglobin &gt;11 g/dL or ≥ 50% increase from Baseline. PR-L: meeting PR criteria; however, a lymphocytosis related to treatment may be present. nPR: All criteria for a CR/CRi were fulfilled, but the bone marrow showed lymphoid nodules.</description>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.0" lower_limit="18.9" upper_limit="92.4"/>
                    <measurement group_id="O2" value="93.3" lower_limit="80.5" upper_limit="98.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)</title>
        <description>Treatment-emergent AEs are defined as 1 or both of the following:&#xD;
Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug&#xD;
Any AEs leading to discontinuation of study drug&#xD;
A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.</description>
        <time_frame>First dose date up to the last dose date (maximum: 105 weeks) plus 30 days</time_frame>
        <population>The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Tirabrutinib + Idelalisib</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tirabrutinib + Idelalisib + Obinutuzumab</title>
            <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)</title>
          <description>Treatment-emergent AEs are defined as 1 or both of the following:&#xD;
Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug&#xD;
Any AEs leading to discontinuation of study drug&#xD;
A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.</description>
          <population>The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.</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="5"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any Treatment-Emergent AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                    <measurement group_id="O2" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-Emergent SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.0"/>
                    <measurement group_id="O2" value="46.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months</time_frame>
      <desc>Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.&#xD;
All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tirabrutinib + Idelalisib</title>
          <description>Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Tirabrutinib + Idelalisib + Obinutuzumab</title>
          <description>Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses administered intravenously over 21 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.1</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="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Coronary artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Atypical pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Large intestine infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Investigation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Tumour lysis syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Acute myeloid leukaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Ureterolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.1</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="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="30"/>
              </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="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diverticulum intestinal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Feeling cold</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Medical device pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus infection reactivation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Febrile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Herpes virus infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oral pustule</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </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="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </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="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Groin pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Spinal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </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="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nasal mucosal disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin exfoliation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </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>After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:&#xD;
The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or&#xD;
The study has been completed at all study sites for at least 2 years</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gilead Clinical Study Information Center</name_or_title>
      <organization>Gilead Sciences</organization>
      <phone>1-833-445-3230 (GILEAD-0)</phone>
      <email>GileadClinicalTrials@gilead.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/NCT02968563
org study id: GS-US-401-1958
secondary id: 2015-003909-42
secondary id: CLLRUmbrella1
nct id: NCT02968563
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The primary objective of this study is to determine the preliminary efficacy of the
      combination of tirabrutinib and idelalisib with obinutuzumab in adults with relapsed or
      refractory chronic lymphocytic leukemia (CLL).

      The study has a 6 participant per arm safety run-in to evaluate safety prior to the
      enrollment of subsequent participants. The treatment period is adaptive, with a duration of
      active treatment up to two years and a total follow-up on study for up to 30 days post end of
      treatment, or up to Week 25 should a participant discontinue treatment prior to Week 25 for
      reasons other than disease progression.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of Complete Response/Complete Remission (CR), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25
time frame: Week 25
description: Rate of CR per modified IWCLL 2008 criteria at Week 25 was defined as the percentage of participants who achieved CR/complete remission with incomplete recovery of the bone marrow (CRi) at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.
measure: Rate of CR With Bone Marrow Minimal Residual Disease (CR/BM MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25
time frame: Week 25
description: Rate of CR/BM MRD at Week 25 was defined as percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved BM MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with four-color-flow cytometry (FACS) and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,<10^-4 and participants were defined as MRD negative if their disease burden was below this threshold.
measure: Rate of CR With Peripheral Minimal Residual Disease (CR/PB MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25
time frame: Week 25
description: Rate of CR/PB MRD at Week 25 was defined as the percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved PB MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with FACS and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,<10^-4 and participants were defined as MRD negative if their disease burden was below this threshold.
measure: Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25
time frame: Week 25
description: ORR was assessed based on modified IWCLL 2008 criteria and was defined as percentage of participants achieving a CR, CRi, partial remission (PR; including nodular partial response [nPR]), and PR with lymphocytosis (PR-L). CR and CRi: meeting all the criteria that have been defined in Outcome measures 1, 2 and 3. PR: ≥ 2 of these: ≥ 50% decrease in lymphocytes, lymphadenopathy, size of liver, size of spleen, and 50% decrease in bone marrow infiltrates; and ≥ 1 of these: neutrophils > 1500/μL or ≥ 50% increase from Baseline, platelets ≥ 100,000/µL or ≥ 50% increase from Baseline, hemoglobin >11 g/dL or ≥ 50% increase from Baseline. PR-L: meeting PR criteria; however, a lymphocytosis related to treatment may be present. nPR: All criteria for a CR/CRi were fulfilled, but the bone marrow showed lymphoid nodules.
measure: Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
time frame: First dose date up to the last dose date (maximum: 105 weeks) plus 30 days
description: Treatment-emergent AEs are defined as 1 or both of the following:
Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug
Any AEs leading to discontinuation of study drug
A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.
arm group label: Tirabrutinib + Idelalisib
arm group type: Experimental
description: Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks.
arm group label: Tirabrutinib + Idelalisib + Obinutuzumab
arm group type: Experimental
description: Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.
intervention type: Drug
intervention name: Tirabrutinib
description: Tablets administered orally
arm group label: Tirabrutinib + Idelalisib
arm group label: Tirabrutinib + Idelalisib + Obinutuzumab
other name: GS-4059
intervention type: Drug
intervention name: Idelalisib
description: Tablets administered orally
arm group label: Tirabrutinib + Idelalisib
arm group label: Tirabrutinib + Idelalisib + Obinutuzumab
other name: Zydelig®
other name: GS-1101
other name: CAL-101
intervention type: Drug
intervention name: Obinutuzumab
description: Administered intravenously
arm group label: Tirabrutinib + Idelalisib + Obinutuzumab
other name: Gazyvaro®
other name: Gazyva®
other name: GA101
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
facility: 
facility: 
facility: 
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facility: 
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facility: 
facility: 
country: Germany
url: http://www.dcllsg.de/studie/cllrUmbrella1/
description: Click here for more information about this study: CLLRUmbrella1 (German CLL Study Group)
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Obinutuzumab
mesh term: Idelalisib
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 