<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/NCT03817853</url>
  </required_header>
  <id_info>
    <org_study_id>MO40597</org_study_id>
    <secondary_id>2018-003255-38</secondary_id>
    <nct_id>NCT03817853</nct_id>
  </id_info>
  <brief_title>An Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion in Patients With Previously Untreated Advanced Follicular Lymphoma</brief_title>
  <official_title>A Multicentric, Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion (SDI) in Patients With Previously Untreated Advanced Follicular Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This open-label, single arm study will evaluate the safety of obinutuzumab administered as a&#xD;
      short duration infusion (SDI; target 90-minute infusion) during cycle 2 and from cycle 2&#xD;
      onwards in combination with chemotherapy in participants with previously untreated advanced&#xD;
      follicular lymphoma (FL). The study has two phases: in the first phase, participants will&#xD;
      receive the first cycle of obinutuzumab-based chemotherapy (G-chemo) induction therapy as&#xD;
      usual with the first three infusions of obinutuzumab (1000 mg) administered at the regular&#xD;
      infusion rate on Day 1, 8, and 15 of cycle 1. Phase 2 starts when participants who do not&#xD;
      experience any Grade ≥ 3 infusion related reactions during the first cycle receive their&#xD;
      first obintuzumab infusion given at the faster infusion rate in Cycle 2. For Cycle 2, Day 1&#xD;
      and all other following infusions (including maintenance), obinutuzumab will be administered&#xD;
      at a faster infusion of 90-minute SDI, as long as the participant does not experience any&#xD;
      Grade ≥ 3 infusion related reactions. The investigator is free to choose the chemotherapy for&#xD;
      each participant (bendamustine, CHOP [cyclophosphamide, doxorubicin, vincristine,&#xD;
      prednisone/prednisolone/methylprednisolone], or CVP [cyclophosphamide, vincristine, and&#xD;
      prednisone/prednisolone/methylprednisolone]). The total number of cycles of G-chemo induction&#xD;
      therapy and the cycles length depends on the chemotherapy chosen for each participant.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 26, 2019</start_date>
  <completion_date type="Actual">January 25, 2023</completion_date>
  <primary_completion_date type="Actual">August 4, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Grade &gt;=3 Infusion-Related Reactions (IRRs) During Cycle 2 in Patients Who Had Previously Received Obinutuzumab at the Standard Infusion Rate During Cycle 1 Without Experiencing a Grade 3 or 4 IRR</measure>
    <time_frame>Within 24 hours from the end of study treatment infusion of Day 1 in Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)</time_frame>
    <description>IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events (AEs)</measure>
    <time_frame>Baseline up to clinical cut off date (up to approximately 1.5 years)</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product, regardless of causal attribution. An AE was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study, recurrence of an intermittent medical condition, deterioration in a laboratory value or other clinical test or were related to a protocol-mandated intervention were also considered AEs. Grading was completed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of IRRs Regardless of Grade by Cycle</measure>
    <time_frame>Within 24 hours from the end of study treatment infusion in all cycles, including maintenance ((1 cycle: 21 or 28 days depending on the chemotherapy selected); up to approximately 2.5 years)</time_frame>
    <description>IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to IRR From Infusion to Onset of the IRR During Cycle 2</measure>
    <time_frame>From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)</time_frame>
    <description>Time to IRR (of any grade) in Cycle 2 was defined as the time from the start of infusion (i.e., start date/time of infusion of the first component of study treatment) in Cycle 2 to the onset of the IRR (of any grade) during Cycle 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration (In Minutes) of Obinutuzumab Administration by Cycle</measure>
    <time_frame>All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)</time_frame>
    <description>The duration of obinutuzumab administration (in minutes) by cycle was defined as the difference between the end time and the start time of obinutuzumab administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type of Grade &gt;=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle</measure>
    <time_frame>All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Grade &gt;=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle</measure>
    <time_frame>All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)</time_frame>
    <description>The duration, in minutes, of IRRs during all cycles, where obinutuzumab was administered as an SDI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) at the End of Induction (EOI) Therapy</measure>
    <time_frame>Baseline up to end of induction therapy (up to approximately 6 months)</time_frame>
    <description>ORR at EOI therapy was defined as the percentage of particpants with either a CR, CR unconfirmed or PR at the EOI visit, as determined by the investigator and according to the guidelines used at the site.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) Rate at the End of the Study</measure>
    <time_frame>Baseline up to end of study (up to approximately 4 years)</time_frame>
    <description>PFS was defined as the time from start of treatment to the first occurrence of disease progression as assessed by the investigator according to the guidelines used at the site or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) at the End of the Study</measure>
    <time_frame>Baseline up to end of study (up to approximately 4 years)</time_frame>
    <description>OS was defined as the time from start of treatment (date of first intake of any study treatment component) to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Response (CR) Rate at 30 Months (CR30), as Assessed by the Investigator and According to the Guidelines Used at the Site</measure>
    <time_frame>Baseline up to 30 months</time_frame>
    <description>The CR30 rate was defined as the percentage of participants with a CR at 30 months from study treatment initiation (date of first intake of any study treatment component), as determined by the investigator according to the guidelines used at the site.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">114</enrollment>
  <condition>Advanced Follicular Lymphoma</condition>
  <arm_group>
    <arm_group_label>Obinutuzumab+Chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator is free to choose the chemotherapy for each patient. Obinutuzumab and chemotherapy is administered during induction phase and obinutuzumab monotherapy is administered during maintenance phase.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Obinutuzumab</intervention_name>
    <description>Obinutuzumab 1000 mg IV infusion, administered on Day 1, 8 and 15 during Cycle 1, and on Day 1 of subsequent cycles, for 6-8 cycles. Each cycle is 21 or 28 days long depending on the chemotherapy regimen allocated. Maintenance obinutuzumab monotherapy in patients who achieve at least a partial response, after induction therapy will be administered a dose of 1000 mg once every 8 weeks for 2 years or until disease progression (whichever occurs first).</description>
    <arm_group_label>Obinutuzumab+Chemotherapy</arm_group_label>
    <other_name>GA101, RO5072759</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bendamustine</intervention_name>
    <description>Bendamustine will be administered on Days 1 and 2 for Cycles 1-6 at a dose of 90 mg/m2/day, for six 28-day cycles.</description>
    <arm_group_label>Obinutuzumab+Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.</description>
    <arm_group_label>Obinutuzumab+Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle, for six cycles.</description>
    <arm_group_label>Obinutuzumab+Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone/Prednisolone/Methylprednisolone</intervention_name>
    <description>Prednisone 100 mg (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.</description>
    <arm_group_label>Obinutuzumab+Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.</description>
    <arm_group_label>Obinutuzumab+Chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with previously untreated Stage III or IV FL or Stage II bulky disease&#xD;
             scheduled to receive obinutuzumab plus chemotherapy due to at least one of the&#xD;
             following criteria: a.) Bulky disease, defined as a nodal or extranodal (except&#xD;
             spleen) mass&#xD;
&#xD;
             ≥ 7 cm in the greatest diameter b.) Local symptoms or compromise of normal organ&#xD;
             function due to progressive nodal disease or extranodal tumor mass c.) Presence of B&#xD;
             symptoms (fever [&gt; 38ºC], drenching night sweats, or unintentional weight loss of &gt;&#xD;
             10% of normal body weight over a period of 6 months or less) d.) Presence of&#xD;
             symptomatic extranodal disease (e.g., pleural effusions, peritoneal ascites) e.)&#xD;
             Cytopenias due to underlying lymphoma (i.e., absolute neutrophil count &lt; 1.0 × 109/L,&#xD;
             hemoglobin &lt; 10 g/dL, and/or platelet count &lt; 100 × 109/L) f.) Involvement of ≥ 3&#xD;
             nodal sites, each with a diameter of ≥ 3 cm g.) Symptomatic splenic enlargement&#xD;
&#xD;
          -  Histologically documented CD-20-positive FL, as determined by the local laboratory&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Adequate hematologic function (unless abnormalities are related to FL)&#xD;
&#xD;
          -  Life expectancy of ≥ 12 months&#xD;
&#xD;
          -  For women who are not postmenopausal (≥ 12 consecutive months of non-therapy-induced&#xD;
             amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to&#xD;
             remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods&#xD;
             that result in a failure rate of &lt; 1% per year during the treatment period and for at&#xD;
             least 18 months after the last dose of obinutuzumab, for at least 3 months after the&#xD;
             last dose of bendamustine or according to institutional guidelines for CHOP or CVP&#xD;
             chemotherapy, whichever is longer&#xD;
&#xD;
          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use&#xD;
             contraceptive measures and agreement to refrain from donating sperm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Relapsed / refractory FL&#xD;
&#xD;
          -  Prior treatment for FL with chemotherapy, radiotherapy, or immunotherapy&#xD;
&#xD;
          -  Grade IIIb FL&#xD;
&#xD;
          -  Histological evidence of transformation of FL into high-grade B-cell NHL&#xD;
&#xD;
          -  Treatment with systemic immunosuppressive medications, including, but not limited to,&#xD;
             prednisone/prednisolone/methylprednisolone (at a dose equivalent to &gt;30 mg/day&#xD;
             prednisone), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor&#xD;
             agents within 2 weeks prior to Day 1 of Cycle 1&#xD;
&#xD;
          -  History of solid organ transplantation&#xD;
&#xD;
          -  History of anti-CD20 antibody therapy&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine&#xD;
             monoclonal antibodies&#xD;
&#xD;
          -  Known sensitivity or allergy to murine products&#xD;
&#xD;
          -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells&#xD;
             or any of the study drugs&#xD;
&#xD;
          -  Active bacterial, viral, fungal, or other infection or any major episode of infection&#xD;
             requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1&#xD;
&#xD;
          -  Positive test results for chronic HBV infection (defined as positive HBsAg serology)&#xD;
&#xD;
          -  Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology&#xD;
             testing)&#xD;
&#xD;
          -  Known history of HIV positive status&#xD;
&#xD;
          -  History of progressive multifocal leukoencephalopathy (PML)&#xD;
&#xD;
          -  Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1 or&#xD;
             anticipation that such a live, attenuated vaccine will be required during the study&#xD;
&#xD;
          -  History of prior other malignancy with the exception of: a. Curatively treated&#xD;
             carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the&#xD;
             breast, basal- or squamous-cell skin cancer, Stage I melanoma, or low-grade,&#xD;
             early-stage localized prostate cancer b. Any previously treated malignancy that has&#xD;
             been in remission without treatment for ≥ 2 years prior to enrollment&#xD;
&#xD;
          -  Evidence of any significant, uncontrolled concomitant disease that could affect&#xD;
             compliance with the protocol or interpretation of results, including significant&#xD;
             cardiovascular disease (such as New York Heart Association Class III or IV cardiac&#xD;
             disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or&#xD;
             unstable angina) or significant pulmonary disease (such as obstructive pulmonary&#xD;
             disease or history of bronchospasm)&#xD;
&#xD;
          -  Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of&#xD;
             Cycle 1, Day 1, or anticipation of a major surgical procedure during the course of the&#xD;
             study&#xD;
&#xD;
          -  Any of the following abnormal laboratory values:&#xD;
&#xD;
               1. Creatinine &gt; 1.5 × the upper limit of normal (ULN) (unless creatinine clearance&#xD;
                  normal) or creatinine clearance &lt; 40 mL/min&#xD;
&#xD;
               2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt; 2.5 × ULN&#xD;
&#xD;
               3. Total bilirubin ≥ 1.5 × the ULN: Patients with documented Gilbert disease may be&#xD;
                  enrolled if total bilirubin is ≤ 3.0 × the ULN.&#xD;
&#xD;
               4. International normalized ratio (INR) &gt; 1.5 in the absence of therapeutic&#xD;
                  anticoagulation&#xD;
&#xD;
               5. Partial thromboplastin time or activated partial thromboplastin time &gt; 1.5 × ULN&#xD;
                  in the absence of a lupus anticoagulant&#xD;
&#xD;
          -  For patients who will be receiving CHOP: left ventricular ejection fraction (LVEF) &lt;&#xD;
             50% by multigated acquisition (MUGA) scan or echocardiogram&#xD;
&#xD;
          -  Pregnant or lactating, or intending to become pregnant during the study&#xD;
&#xD;
          -  Any investigational therapy within 28 days prior to the start of Cycle 1&#xD;
&#xD;
          -  Positive test results for human T-lymphotropic virus 1 (HTLV-1)&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Center; Medical Oncology</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Oncology Partners of Maryland, PA</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817-1915</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summit Medical Center</name>
      <address>
        <city>Florham Park</city>
        <state>New Jersey</state>
        <zip>07932</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Juan Oncology Associates</name>
      <address>
        <city>Farmington</city>
        <state>New Mexico</state>
        <zip>87401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willamette Valley Cancer Ctr - 520 Country Club</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97401-8122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Onc-Central Austin CA Ct</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology Cancer Center</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NOHC - Núcleo de Oncologia e Hematologia do Ceará</name>
      <address>
        <city>Fortaleza</city>
        <state>CE</state>
        <zip>60115-281</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clinicas - UFRGS</name>
      <address>
        <city>Porto Alegre</city>
        <state>RS</state>
        <zip>90035-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Pesquisas Oncologicas - CEPON</name>
      <address>
        <city>Florianopolis</city>
        <state>SC</state>
        <zip>88034-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Amaral Carvalho</name>
      <address>
        <city>Jau</city>
        <state>SP</state>
        <zip>17210-120</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Hämatologie und Onkologie</name>
      <address>
        <city>Chemnitz</city>
        <zip>09113</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Städtisches Klinikum Dessau</name>
      <address>
        <city>Dessau-Roßlau</city>
        <zip>06847</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Frankfurt; Medizinische Klinik II; Onkologie</name>
      <address>
        <city>Frankfurt</city>
        <zip>60596</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OncoResearch Lerchenfeld GmbH</name>
      <address>
        <city>Hamburg</city>
        <zip>22081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik der Uni zu Köln; I. Med. Klinik</name>
      <address>
        <city>Köln</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MVZ Dr. Vehling-Kaiser GmbH; Onkologische Praxis</name>
      <address>
        <city>Landshut</city>
        <zip>84036</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onkologische Schwerpunktpraxis Lübeck</name>
      <address>
        <city>Lübeck</city>
        <zip>23562</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chiba Cancer Center</name>
      <address>
        <city>Chiba</city>
        <zip>260-8717</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hokkaido University Hospital</name>
      <address>
        <city>Hokkaido</city>
        <zip>060-8648</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe City Medical Center General Hospital</name>
      <address>
        <city>Hyogo</city>
        <zip>650-0047</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cancer Institute Hospital of JFCR</name>
      <address>
        <city>Tokyo</city>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Schweitzer Ziekenhuis - loc Dordrecht</name>
      <address>
        <city>Dordrecht</city>
        <zip>3318 AT</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martini Ziekenhuis</name>
      <address>
        <city>Groningen</city>
        <zip>9728 MG</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital De Txagorritxu; Servicio de Hematologia</name>
      <address>
        <city>Vitoria</city>
        <state>Alava</state>
        <zip>01009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta del Mar; Servicio de Hematologia</name>
      <address>
        <city>Cádiz</city>
        <state>Cadiz</state>
        <zip>11009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar; Servicio de Hematologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario la Paz; Servicio de Hematologia</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología</name>
      <address>
        <city>Murcia</city>
        <zip>30008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Wales</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital</name>
      <address>
        <city>Portsmouth</city>
        <zip>PO6 3LY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Cornwall Hospital</name>
      <address>
        <city>Truro</city>
        <zip>TR1 3LQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Germany</country>
    <country>Japan</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <results_first_submitted>July 16, 2021</results_first_submitted>
  <results_first_submitted_qc>August 20, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 24, 2021</results_first_posted>
  <last_update_submitted>February 21, 2023</last_update_submitted>
  <last_update_submitted_qc>February 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Bendamustine Hydrochloride</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Obinutuzumab</mesh_term>
  </intervention_browse>
  <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>September 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03817853/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 12, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03817853/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 35 sites across 7 countries.</recruitment_details>
      <pre_assignment_details>Of the all participants population (114 participants), one participant did not receive the study treatment, thus the safety-evaluable population included 113 participants.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Participants</title>
          <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
        </group>
        <group group_id="P2">
          <title>Maintenance</title>
          <description>Participants who achieved a partial response (PR) or complete response (CR) following the induction phase received obinutuzumab maintenance therapy. 1000 mg of obinutuzumab as single agent was administered as an SDI every 8 weeks (+ or - 10 days) for 2 years or until disease progression).</description>
        </group>
        <group group_id="P3">
          <title>Follow-up</title>
          <description>Participants with stable disease (SD) or progressive disease (PD) as best response after induction therapy discontinued study treatment and underwent a safety follow-up visit at 3 months (90 days (+ or - 10 days)). All participants were followed up at 3 months (90 days (+ or - 10 days)) from the time of the last dose of study treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Induction Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="113"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Measures due to covid19; transformation to double hit high-grade b lymphoma; discontinuation of trt.</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Continuing on Study</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Maintenance/ Follow-up Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="56"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="56"/>
                <participants group_id="P3" count="6"/>
              </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="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Continuing on Study</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="52"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The all participants population includes all enrolled participants.</population>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="113"/>
          </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="58.9" spread="12.7"/>
                  </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="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Race</description>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Ethnicity</description>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Grade &gt;=3 Infusion-Related Reactions (IRRs) During Cycle 2 in Patients Who Had Previously Received Obinutuzumab at the Standard Infusion Rate During Cycle 1 Without Experiencing a Grade 3 or 4 IRR</title>
        <description>IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.</description>
        <time_frame>Within 24 hours from the end of study treatment infusion of Day 1 in Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)</time_frame>
        <population>The Short Duration Infusion (SDI) population included all enrolled particpants who did not experience a Grade 3 or 4 IRR during cycle 1 (i.e. at any of the three Cycle 1 infusions), received obinutuzumab given at the standard rate only during Cycle 1, and received obinutuzumab as an SDI at cycle 2.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Grade &gt;=3 Infusion-Related Reactions (IRRs) During Cycle 2 in Patients Who Had Previously Received Obinutuzumab at the Standard Infusion Rate During Cycle 1 Without Experiencing a Grade 3 or 4 IRR</title>
          <description>IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.</description>
          <population>The Short Duration Infusion (SDI) population included all enrolled particpants who did not experience a Grade 3 or 4 IRR during cycle 1 (i.e. at any of the three Cycle 1 infusions), received obinutuzumab given at the standard rate only during Cycle 1, and received obinutuzumab as an SDI at cycle 2.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.00" upper_limit="3.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Adverse Events (AEs)</title>
        <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product, regardless of causal attribution. An AE was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study, recurrence of an intermittent medical condition, deterioration in a laboratory value or other clinical test or were related to a protocol-mandated intervention were also considered AEs. Grading was completed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.</description>
        <time_frame>Baseline up to clinical cut off date (up to approximately 1.5 years)</time_frame>
        <population>The safety population included all participants who received at least one dose of obinutuzumab.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
          </group>
          <group group_id="O2">
            <title>Maintenance: Obinutuzumab</title>
            <description>Participants received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.&#xD;
Participants who achieved a partial response (PR) or complete response (CR) following the induction phase received obinutuzumab maintenance therapy. 1000 mg of obinutuzumab as single agent was administered as an SDI every 8 weeks (+ or - 10 days) for 2 years or until disease progression).</description>
          </group>
          <group group_id="O3">
            <title>Follow-up</title>
            <description>Participants with stable disease (SD) or progressive disease (PD) as best response after induction therapy discontinued study treatment and underwent a safety follow-up visit at 3 months (90 days (+ or - 10 days)). All participants were followed up at 3 months (90 days (+ or - 10 days)) from the time of the last dose of study treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events (AEs)</title>
          <description>An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product, regardless of causal attribution. An AE was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study, recurrence of an intermittent medical condition, deterioration in a laboratory value or other clinical test or were related to a protocol-mandated intervention were also considered AEs. Grading was completed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.</description>
          <population>The safety population included all participants who received at least one dose of obinutuzumab.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="56"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.1"/>
                    <measurement group_id="O2" value="41.1"/>
                    <measurement group_id="O3" value="35.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of IRRs Regardless of Grade by Cycle</title>
        <description>IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.</description>
        <time_frame>Within 24 hours from the end of study treatment infusion in all cycles, including maintenance ((1 cycle: 21 or 28 days depending on the chemotherapy selected); up to approximately 2.5 years)</time_frame>
        <population>The safety population included all participants who received at least one dose of obinutuzumab.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of IRRs Regardless of Grade by Cycle</title>
          <description>IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.</description>
          <population>The safety population included all participants who received at least one dose of obinutuzumab.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="113"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="111"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="84"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to IRR From Infusion to Onset of the IRR During Cycle 2</title>
        <description>Time to IRR (of any grade) in Cycle 2 was defined as the time from the start of infusion (i.e., start date/time of infusion of the first component of study treatment) in Cycle 2 to the onset of the IRR (of any grade) during Cycle 2.</description>
        <time_frame>From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)</time_frame>
        <population>The SDI population (97 participants) included all enrolled particpants who did not experience a Grade 3 or 4 IRR during cycle 1 (i.e. at any of the three Cycle 1 infusions), received obinutuzumab given at the standard rate only during Cycle 1, and received obinutuzumab as an SDI at cycle 2. For this outcome measure, only one participant was analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to IRR From Infusion to Onset of the IRR During Cycle 2</title>
          <description>Time to IRR (of any grade) in Cycle 2 was defined as the time from the start of infusion (i.e., start date/time of infusion of the first component of study treatment) in Cycle 2 to the onset of the IRR (of any grade) during Cycle 2.</description>
          <population>The SDI population (97 participants) included all enrolled particpants who did not experience a Grade 3 or 4 IRR during cycle 1 (i.e. at any of the three Cycle 1 infusions), received obinutuzumab given at the standard rate only during Cycle 1, and received obinutuzumab as an SDI at cycle 2. For this outcome measure, only one participant was analyzed.</population>
          <units>Hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.800" spread="NA">Standard deviation (SD) is not available because only 1 participant had the time to IRR recorded and the SD for one value is not defined.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration (In Minutes) of Obinutuzumab Administration by Cycle</title>
        <description>The duration of obinutuzumab administration (in minutes) by cycle was defined as the difference between the end time and the start time of obinutuzumab administration.</description>
        <time_frame>All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)</time_frame>
        <population>The safety population included all participants who received at least one dose of obinutuzumab.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration (In Minutes) of Obinutuzumab Administration by Cycle</title>
          <description>The duration of obinutuzumab administration (in minutes) by cycle was defined as the difference between the end time and the start time of obinutuzumab administration.</description>
          <population>The safety population included all participants who received at least one dose of obinutuzumab.</population>
          <units>Minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle(C) 1 Day(D) 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="295.96" spread="147.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C1D8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="215.97" spread="46.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C1D15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="207.52" spread="35.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101.48" spread="20.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="102.97" spread="65.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.33" spread="10.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.26" spread="17.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.49" spread="12.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.56" spread="14.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.54" spread="10.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maintenance Week 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101.48" spread="21.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maintenance Week 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.21" spread="11.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maintenance Week 17</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.64" spread="7.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maintenance Week 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.83" spread="3.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maintenance Week 33</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.50" spread="2.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maintenance Week 41</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Type of Grade &gt;=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle</title>
        <time_frame>All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)</time_frame>
        <population>The safety population included all participants who received at least one dose of obinutuzumab. Only 1 participant had a Grade &gt;=3 IRR, with 3 symptoms in Cycle 5. Weight increased was a grade 1 symptom belonging to the grade 3 IRRs.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Type of Grade &gt;=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle</title>
          <population>The safety population included all participants who received at least one dose of obinutuzumab. Only 1 participant had a Grade &gt;=3 IRR, with 3 symptoms in Cycle 5. Weight increased was a grade 1 symptom belonging to the grade 3 IRRs.</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="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle (C) 5- Hypertension</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C5 - Renal failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C5 - Weight increased</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Grade &gt;=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle</title>
        <description>The duration, in minutes, of IRRs during all cycles, where obinutuzumab was administered as an SDI.</description>
        <time_frame>All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)</time_frame>
        <population>The safety population (113 participants) included all participants who received at least one dose of obinutuzumab. For this outcome measure, only one participant was analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Grade &gt;=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle</title>
          <description>The duration, in minutes, of IRRs during all cycles, where obinutuzumab was administered as an SDI.</description>
          <population>The safety population (113 participants) included all participants who received at least one dose of obinutuzumab. For this outcome measure, only one participant was analyzed.</population>
          <units>Minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="165.0" spread="NA">SD is not available because only 1 participant had the duration of IRR recorded and the SD for one value is not defined.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) at the End of Induction (EOI) Therapy</title>
        <description>ORR at EOI therapy was defined as the percentage of particpants with either a CR, CR unconfirmed or PR at the EOI visit, as determined by the investigator and according to the guidelines used at the site.</description>
        <time_frame>Baseline up to end of induction therapy (up to approximately 6 months)</time_frame>
        <population>The safety population included all participants who received at least one dose of obinutuzumab.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) at the End of Induction (EOI) Therapy</title>
          <description>ORR at EOI therapy was defined as the percentage of particpants with either a CR, CR unconfirmed or PR at the EOI visit, as determined by the investigator and according to the guidelines used at the site.</description>
          <population>The safety population included all participants who received at least one dose of obinutuzumab.</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="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival (PFS) Rate at the End of the Study</title>
        <description>PFS was defined as the time from start of treatment to the first occurrence of disease progression as assessed by the investigator according to the guidelines used at the site or death from any cause.</description>
        <time_frame>Baseline up to end of study (up to approximately 4 years)</time_frame>
        <posting_date>09/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) at the End of the Study</title>
        <description>OS was defined as the time from start of treatment (date of first intake of any study treatment component) to death from any cause.</description>
        <time_frame>Baseline up to end of study (up to approximately 4 years)</time_frame>
        <posting_date>09/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Complete Response (CR) Rate at 30 Months (CR30), as Assessed by the Investigator and According to the Guidelines Used at the Site</title>
        <description>The CR30 rate was defined as the percentage of participants with a CR at 30 months from study treatment initiation (date of first intake of any study treatment component), as determined by the investigator according to the guidelines used at the site.</description>
        <time_frame>Baseline up to 30 months</time_frame>
        <posting_date>09/2023</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to clinical cut off date (up to approximately 1.5 years)</time_frame>
      <desc>An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product, regardless of causal attribution. Grading was completed according to the CTCAE, version 5.0.</desc>
      <group_list>
        <group group_id="E1">
          <title>All Participants</title>
          <description>Participants were enrolled in an induction phase and received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator was free to choose the chemotherapy for each participant.</description>
        </group>
        <group group_id="E2">
          <title>Maintenance</title>
          <description>Participants who achieved a partial response (PR) or complete response (CR) following the induction phase received obinutuzumab maintenance therapy. 1000 mg of obinutuzumab as single agent was administered as an SDI every 8 weeks (+ or - 10 days) for 2 years or until disease progression).</description>
        </group>
        <group group_id="E3">
          <title>Follow-up</title>
          <description>Participants with stable disease (SD) or progressive disease (PD) as best response after induction therapy discontinued study treatment and underwent a safety follow-up visit at 3 months (90 days (+ or - 10 days)). All participants were followed up at 3 months (90 days (+ or - 10 days)) from the time of the last dose of study treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="56"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Cardiorenal syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Escherichia urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Herpes zoster disseminated</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neutropenic sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pneumonia streptococcal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lumbar vertebral fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Bowen's disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Double hit lymphoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Metastatic bronchial carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="111" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="56"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="23" subjects_affected="20" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="28" subjects_affected="15" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="33" subjects_affected="22" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="104" subjects_affected="63" subjects_at_risk="113"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="23" subjects_affected="17" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="12" subjects_affected="10" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="42" subjects_affected="39" subjects_at_risk="113"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="14" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="60" subjects_affected="45" subjects_at_risk="113"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="113"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="18" subjects_affected="17" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="15" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="14" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="126" subjects_affected="67" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="17" subjects_affected="14" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="14" subjects_affected="11" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="20" subjects_affected="19" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" events="19" subjects_affected="18" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="13" subjects_affected="9" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="17" subjects_affected="17" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="56"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800 821-8590</phone>
      <email>genentech@druginfo.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/NCT03817853
org study id: MO40597
secondary id: 2018-003255-38
nct id: NCT03817853
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This open-label, single arm study will evaluate the safety of obinutuzumab administered as a
      short duration infusion (SDI; target 90-minute infusion) during cycle 2 and from cycle 2
      onwards in combination with chemotherapy in participants with previously untreated advanced
      follicular lymphoma (FL). The study has two phases: in the first phase, participants will
      receive the first cycle of obinutuzumab-based chemotherapy (G-chemo) induction therapy as
      usual with the first three infusions of obinutuzumab (1000 mg) administered at the regular
      infusion rate on Day 1, 8, and 15 of cycle 1. Phase 2 starts when participants who do not
      experience any Grade ≥ 3 infusion related reactions during the first cycle receive their
      first obintuzumab infusion given at the faster infusion rate in Cycle 2. For Cycle 2, Day 1
      and all other following infusions (including maintenance), obinutuzumab will be administered
      at a faster infusion of 90-minute SDI, as long as the participant does not experience any
      Grade ≥ 3 infusion related reactions. The investigator is free to choose the chemotherapy for
      each participant (bendamustine, CHOP [cyclophosphamide, doxorubicin, vincristine,
      prednisone/prednisolone/methylprednisolone], or CVP [cyclophosphamide, vincristine, and
      prednisone/prednisolone/methylprednisolone]). The total number of cycles of G-chemo induction
      therapy and the cycles length depends on the chemotherapy chosen for each participant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Grade >=3 Infusion-Related Reactions (IRRs) During Cycle 2 in Patients Who Had Previously Received Obinutuzumab at the Standard Infusion Rate During Cycle 1 Without Experiencing a Grade 3 or 4 IRR
time frame: Within 24 hours from the end of study treatment infusion of Day 1 in Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
description: IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.
measure: Percentage of Participants With Adverse Events (AEs)
time frame: Baseline up to clinical cut off date (up to approximately 1.5 years)
description: An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product, regardless of causal attribution. An AE was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study, recurrence of an intermittent medical condition, deterioration in a laboratory value or other clinical test or were related to a protocol-mandated intervention were also considered AEs. Grading was completed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
measure: Percentage of IRRs Regardless of Grade by Cycle
time frame: Within 24 hours from the end of study treatment infusion in all cycles, including maintenance ((1 cycle: 21 or 28 days depending on the chemotherapy selected); up to approximately 2.5 years)
description: IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.
measure: Time to IRR From Infusion to Onset of the IRR During Cycle 2
time frame: From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
description: Time to IRR (of any grade) in Cycle 2 was defined as the time from the start of infusion (i.e., start date/time of infusion of the first component of study treatment) in Cycle 2 to the onset of the IRR (of any grade) during Cycle 2.
measure: Duration (In Minutes) of Obinutuzumab Administration by Cycle
time frame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
description: The duration of obinutuzumab administration (in minutes) by cycle was defined as the difference between the end time and the start time of obinutuzumab administration.
measure: Type of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle
time frame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
measure: Duration of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle
time frame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
description: The duration, in minutes, of IRRs during all cycles, where obinutuzumab was administered as an SDI.
measure: Objective Response Rate (ORR) at the End of Induction (EOI) Therapy
time frame: Baseline up to end of induction therapy (up to approximately 6 months)
description: ORR at EOI therapy was defined as the percentage of particpants with either a CR, CR unconfirmed or PR at the EOI visit, as determined by the investigator and according to the guidelines used at the site.
measure: Progression-Free Survival (PFS) Rate at the End of the Study
time frame: Baseline up to end of study (up to approximately 4 years)
description: PFS was defined as the time from start of treatment to the first occurrence of disease progression as assessed by the investigator according to the guidelines used at the site or death from any cause.
measure: Overall Survival (OS) at the End of the Study
time frame: Baseline up to end of study (up to approximately 4 years)
description: OS was defined as the time from start of treatment (date of first intake of any study treatment component) to death from any cause.
measure: Complete Response (CR) Rate at 30 Months (CR30), as Assessed by the Investigator and According to the Guidelines Used at the Site
time frame: Baseline up to 30 months
description: The CR30 rate was defined as the percentage of participants with a CR at 30 months from study treatment initiation (date of first intake of any study treatment component), as determined by the investigator according to the guidelines used at the site.
arm group label: Obinutuzumab+Chemotherapy
arm group type: Experimental
description: Participants received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator is free to choose the chemotherapy for each patient. Obinutuzumab and chemotherapy is administered during induction phase and obinutuzumab monotherapy is administered during maintenance phase.
intervention type: Drug
intervention name: Obinutuzumab
description: Obinutuzumab 1000 mg IV infusion, administered on Day 1, 8 and 15 during Cycle 1, and on Day 1 of subsequent cycles, for 6-8 cycles. Each cycle is 21 or 28 days long depending on the chemotherapy regimen allocated. Maintenance obinutuzumab monotherapy in patients who achieve at least a partial response, after induction therapy will be administered a dose of 1000 mg once every 8 weeks for 2 years or until disease progression (whichever occurs first).
arm group label: Obinutuzumab+Chemotherapy
other name: GA101, RO5072759
intervention type: Drug
intervention name: Bendamustine
description: Bendamustine will be administered on Days 1 and 2 for Cycles 1-6 at a dose of 90 mg/m2/day, for six 28-day cycles.
arm group label: Obinutuzumab+Chemotherapy
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.
arm group label: Obinutuzumab+Chemotherapy
intervention type: Drug
intervention name: Doxorubicin
description: Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle, for six cycles.
arm group label: Obinutuzumab+Chemotherapy
intervention type: Drug
intervention name: Prednisone/Prednisolone/Methylprednisolone
description: Prednisone 100 mg (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.
arm group label: Obinutuzumab+Chemotherapy
intervention type: Drug
intervention name: Vincristine
description: Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.
arm group label: Obinutuzumab+Chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Brazil
country: Germany
country: Japan
country: Netherlands
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
mesh term: Prednisone
mesh term: Methylprednisolone
mesh term: Prednisolone
mesh term: Cyclophosphamide
mesh term: Bendamustine Hydrochloride
mesh term: Doxorubicin
mesh term: Vincristine
mesh term: Obinutuzumab
provided document: 
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certain agreements: 
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