<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/NCT02220842</url>
  </required_header>
  <id_info>
    <org_study_id>GO29383</org_study_id>
    <secondary_id>2014-001812-21</secondary_id>
    <nct_id>NCT02220842</nct_id>
  </id_info>
  <brief_title>A Safety and Pharmacology Study of Atezolizumab (MPDL3280A) Administered With Obinutuzumab or Tazemetostat in Participants With Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-cell Lymphoma</brief_title>
  <official_title>A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Obinutuzumab in Patients With Relapsed/Refractory Follicular Lymphoma or Atezolizumab Administered With Obinutuzumab or Tazemetostat in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This open-label, multicenter, global study is designed to assess the safety, tolerability,&#xD;
      preliminary efficacy, and pharmacokinetics of intravenous atezolizumab (MPDL3280A) and&#xD;
      obinutuzumab in participants with refractory or relapsed follicular lymphoma (FL) or&#xD;
      atezolizumab and obinutuzumab or tazemetostat administered in participants with refractory or&#xD;
      relapsed diffuse large B-cell lymphoma (DLBCL). The anticipated duration of this study is&#xD;
      approximately 4.5 years.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 18, 2014</start_date>
  <completion_date type="Actual">January 21, 2020</completion_date>
  <primary_completion_date type="Actual">January 21, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Phase 2 Dose (RP2D) of Atezolizumab</measure>
    <time_frame>21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Obinutuzumab Minimum Serum Concentration (Cmin)</measure>
    <time_frame>Preinfusion (hour 0) on Day 1, 8, 15 of Cycle 1, Day 1 of Cycles 2, 3, 4, 6, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events (AEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)</measure>
    <time_frame>Baseline up to approximately 4.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Anti-therapeutic Antibody Response to Atezolizumab and Obinutuzumab</measure>
    <time_frame>Baseline up to approximately 4.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atezolizumab Maximum Serum Concentration (Cmax)</measure>
    <time_frame>Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)</time_frame>
    <description>Arm 1: preinfusion (hour 0) on Day 1 of Cycle 1, 30 minutes post end of atezolizumab infusion (infusion over 30-60 minutes) on Day 1 of Cycle 2, preinfusion on Day 1 of Cycles 3, 4, 6, 8, and every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks), additionally preinfusion on Day 1 of Cycle 9; Arm 2: preinfusion (hour 0) and 30 minutes post end of atezolizumab infusion (infusion over 30-60 minutes) on Day 1 of Cycles 1 and 3, preinfusion on Day 1 of Cycles 2, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atezolizumab Minimum Serum Concentration (Cmin)</measure>
    <time_frame>Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)</time_frame>
    <description>Arm 1: preinfusion (hour 0) on Day 1 of Cycles 1, 3, 4, 6, 8, and every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks), pre-infusion on Day 1 of Cycle 9; Arm 2: preinfusion (hour 0) on Day 1 of Cycles 1, 2, 3, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle = 21 days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Obinutuzumab Maximum Serum Concentration (Cmax)</measure>
    <time_frame>Arm 1: Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)</time_frame>
    <description>Arm 1: preinfusion (hour 0) on Day 1, 4-hour post start of infusion on Day 2, preinfusion (hour 0) and 4-hour post start of infusion on Day 8, 15 of Cycle 1, Day 1 of Cycles 2, 3, 4, 6, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Best Overall Response According to Lugano Classification</measure>
    <time_frame>Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Objective Response (Complete Response or Partial Response) According to Lugano Classification</measure>
    <time_frame>Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) According to Lugano Classification</measure>
    <time_frame>Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Baseline until death due to any cause (up to approximately 4.5 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Objective Response (DOR) According to Lugano Classification</measure>
    <time_frame>From first documented complete or partial response up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tazemetostat Plasma Concentrations</measure>
    <time_frame>Arm 2: predose (hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8, every 8 cycles thereafter up to Cycle 17; 1, 2, 4 hours post dose on Day 1 of Cycles 1 and 3; additionally (in Cohort E only) 0.5, 6, 8 hours post dose on Cycle 3 Day 1 (Cycle=21 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">96</enrollment>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relapsed/refractory FL and DLBCL participants will receive obinutuzumab alone on Days 1, 8, and 15 of Cycle 1 (Cycle length = 21 days), followed by atezolizumab and obinutuzumab on Day 1 of Cycles 2-8, and then atezolizumab alone on Day 1 of Cycle 9 and every cycle thereafter until unacceptable toxicities or disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relapsed/refractory FL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relapsed/refractory DLBCL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relapsed/refractory DLBCL participants will receive atezolizumab (on Day 1) and tazemetostat (on Days 1-21) of each 21-day cycle until unacceptable toxicities or disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relapsed/refractory DLBCL participants will receive atezolizumab and tazemetostat as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.</description>
    <arm_group_label>Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab</arm_group_label>
    <arm_group_label>Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab</arm_group_label>
    <arm_group_label>Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab</arm_group_label>
    <arm_group_label>Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat</arm_group_label>
    <arm_group_label>Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat</arm_group_label>
    <other_name>Tecentriq</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Obinutuzumab</intervention_name>
    <description>During safety evaluation stage, obinutuzumab will be administered as 1000 mg IV infusion. During expansion stage, obinutuzumab will be administered as either 1000 mg IV infusion or at dose decided from safety evaluation stage.</description>
    <arm_group_label>Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab</arm_group_label>
    <arm_group_label>Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tazemetostat</intervention_name>
    <description>Tazemetostat 800 mg will be administered orally, twice daily, on Days 1 to 21.</description>
    <arm_group_label>Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab</arm_group_label>
    <arm_group_label>Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat</arm_group_label>
    <arm_group_label>Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat</arm_group_label>
    <other_name>EPZ6438</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically documented, CD20-positive, relapsed or refractory (defined as having&#xD;
             relapsed within 6 months to the previous treatment) FL or DLBCL (including primary&#xD;
             mediastinal large B-cell lymphoma [PMLBCL])&#xD;
&#xD;
          -  Bone marrow biopsy at screening (unless it was performed within 3 months prior to&#xD;
             screening)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2&#xD;
&#xD;
          -  Life expectancy greater than or equal to (&gt;=) 12 weeks&#xD;
&#xD;
          -  Has a QT interval corrected by Fridericia's formula (QTcF) less than or equal to (&lt;=)&#xD;
             480 milliseconds (msec)&#xD;
&#xD;
          -  At least one bi-dimensionally measurable nodal lesion &gt;1.5 cm in its longest diameter&#xD;
             by computed tomography (CT) scan or MRI, as defined by the Lugano Classification&#xD;
&#xD;
          -  Adequate hematologic and end-organ function&#xD;
&#xD;
          -  Archival tumor tissue&#xD;
&#xD;
          -  For women of childbearing potential: agreement to remain abstinent (refrain from&#xD;
             heterosexual intercourse) or use contraceptive methods that result in a failure rate&#xD;
             of &lt; 1% per year during the treatment period and for at least 90 days after the last&#xD;
             dose of atezolizumab or 18 months after the last dose of obinutuzumab, whichever is&#xD;
             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;
          -  Known central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence&#xD;
             of transformation from an indolent lymphoma to a high-grade or DLBCL&#xD;
&#xD;
          -  Grade 3b FL, small lymphocytic lymphoma (SLL), or Waldenström's macroglobulinemia (WM)&#xD;
             or other lymphoma subtypes except as stated in the inclusion criteria&#xD;
&#xD;
          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent&#xD;
             drainage procedures (once monthly or more frequently); participants with indwelling&#xD;
             catheters are eligible&#xD;
&#xD;
          -  Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of&#xD;
             bisphosphonate therapy or denosumab&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy&#xD;
&#xD;
          -  Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste&#xD;
             homolog 2 (EZH2)&#xD;
&#xD;
          -  Regular treatment with corticosteroids within the 2 or 4 weeks prior to the start of&#xD;
             Cycle 1, unless administered for indications other than non-Hodgkin's lymphoma at a&#xD;
             dose equivalent to &lt; 30 mg/day prednisone/prednisolone&#xD;
&#xD;
          -  Pregnant and lactating women&#xD;
&#xD;
          -  History of autoimmune disease&#xD;
&#xD;
          -  Participants with history of confirmed progressive multifocal leukoencephalopathy&#xD;
             (PML)&#xD;
&#xD;
          -  Participants with prior allogeneic bone marrow transplantation or prior solid organ&#xD;
             transplantation&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis&#xD;
             obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active&#xD;
             pneumonitis per chest CT scan at screening. History of radiation pneumonitis in the&#xD;
             radiation field (fibrosis) is allowed&#xD;
&#xD;
          -  Positive test for Human Immunodeficiency Virus (HIV)&#xD;
&#xD;
          -  History of chronic hepatitis B infection or positive test results for active or&#xD;
             chronic hepatitis B or hepatitis C&#xD;
&#xD;
          -  Significant cardiovascular disease, such as cardiac disease (New York Heart&#xD;
             Association Class II or greater), myocardial infarction within the previous 3 months,&#xD;
             unstable arrhythmias, or unstable angina&#xD;
&#xD;
          -  Hypersensitivity or prior treatment with obinutuzumab&#xD;
&#xD;
          -  Fludarabine or Campath within 12 months prior to study entry&#xD;
&#xD;
          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including&#xD;
             anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies&#xD;
&#xD;
          -  Treatment with systemic immunostimulatory agents (including but not limited to&#xD;
             interferon, interleukin-2) within 6 weeks or 5 half-lives of the drug, whichever is&#xD;
             shorter, prior to Cycle 1, Day 1&#xD;
&#xD;
          -  Treatment with systemic immunosuppressive medications, including but not limited to&#xD;
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor&#xD;
             necrosis factor (anti-TNF) agents within 2 weeks prior to Cycle 1, Day 1; inhaled&#xD;
             corticosteroids and mineralocorticoids are allowed&#xD;
&#xD;
          -  Participants with active tuberculosis (TB) will be excluded from the clinical trial&#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>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Neurological Center</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065-6007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UW- Fred Hutchinson Cancer Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Claude Huriez - CHU Lille; Service des maladies du sang</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Eloi</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint-Louis</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre Benite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Freiburg</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Città della Salute e della Scienza di Torino</name>
      <address>
        <city>Torino</city>
        <state>Piemonte</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Hospital</name>
      <address>
        <city>London</city>
        <zip>E1 2EF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>January 22, 2020</last_update_submitted>
  <last_update_submitted_qc>January 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atezolizumab</mesh_term>
    <mesh_term>Obinutuzumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02220842
org study id: GO29383
secondary id: 2014-001812-21
nct id: NCT02220842
lead sponsor: 
This open-label, multicenter, global study is designed to assess the safety, tolerability,
      preliminary efficacy, and pharmacokinetics of intravenous atezolizumab (MPDL3280A) and
      obinutuzumab in participants with refractory or relapsed follicular lymphoma (FL) or
      atezolizumab and obinutuzumab or tazemetostat administered in participants with refractory or
      relapsed diffuse large B-cell lymphoma (DLBCL). The anticipated duration of this study is
      approximately 4.5 years.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Dose Limiting Toxicities (DLTs)
time frame: 21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)
measure: Recommended Phase 2 Dose (RP2D) of Atezolizumab
time frame: 21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)
measure: Obinutuzumab Minimum Serum Concentration (Cmin)
time frame: Preinfusion (hour 0) on Day 1, 8, 15 of Cycle 1, Day 1 of Cycles 2, 3, 4, 6, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)
measure: Percentage of Participants With Adverse Events (AEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
time frame: Baseline up to approximately 4.5 years
measure: Percentage of Participants With Anti-therapeutic Antibody Response to Atezolizumab and Obinutuzumab
time frame: Baseline up to approximately 4.5 years
measure: Atezolizumab Maximum Serum Concentration (Cmax)
time frame: Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)
description: Arm 1: preinfusion (hour 0) on Day 1 of Cycle 1, 30 minutes post end of atezolizumab infusion (infusion over 30-60 minutes) on Day 1 of Cycle 2, preinfusion on Day 1 of Cycles 3, 4, 6, 8, and every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks), additionally preinfusion on Day 1 of Cycle 9; Arm 2: preinfusion (hour 0) and 30 minutes post end of atezolizumab infusion (infusion over 30-60 minutes) on Day 1 of Cycles 1 and 3, preinfusion on Day 1 of Cycles 2, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)
measure: Atezolizumab Minimum Serum Concentration (Cmin)
time frame: Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)
description: Arm 1: preinfusion (hour 0) on Day 1 of Cycles 1, 3, 4, 6, 8, and every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks), pre-infusion on Day 1 of Cycle 9; Arm 2: preinfusion (hour 0) on Day 1 of Cycles 1, 2, 3, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle = 21 days)
measure: Obinutuzumab Maximum Serum Concentration (Cmax)
time frame: Arm 1: Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)
description: Arm 1: preinfusion (hour 0) on Day 1, 4-hour post start of infusion on Day 2, preinfusion (hour 0) and 4-hour post start of infusion on Day 8, 15 of Cycle 1, Day 1 of Cycles 2, 3, 4, 6, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)
measure: Percentage of Participants With Best Overall Response According to Lugano Classification
time frame: Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)
measure: Percentage of Participants With Objective Response (Complete Response or Partial Response) According to Lugano Classification
time frame: Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)
measure: Progression Free Survival (PFS) According to Lugano Classification
time frame: Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)
measure: Overall Survival (OS)
time frame: Baseline until death due to any cause (up to approximately 4.5 years)
measure: Duration of Objective Response (DOR) According to Lugano Classification
time frame: From first documented complete or partial response up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years)
measure: Tazemetostat Plasma Concentrations
time frame: Arm 2: predose (hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8, every 8 cycles thereafter up to Cycle 17; 1, 2, 4 hours post dose on Day 1 of Cycles 1 and 3; additionally (in Cohort E only) 0.5, 6, 8 hours post dose on Cycle 3 Day 1 (Cycle=21 days)
arm group label: Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab
arm group type: Experimental
description: Relapsed/refractory FL and DLBCL participants will receive obinutuzumab alone on Days 1, 8, and 15 of Cycle 1 (Cycle length = 21 days), followed by atezolizumab and obinutuzumab on Day 1 of Cycles 2-8, and then atezolizumab alone on Day 1 of Cycle 9 and every cycle thereafter until unacceptable toxicities or disease progression.
arm group label: Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab
arm group type: Experimental
description: Relapsed/refractory FL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.
arm group label: Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab
arm group type: Experimental
description: Relapsed/refractory DLBCL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.
arm group label: Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat
arm group type: Experimental
description: Relapsed/refractory DLBCL participants will receive atezolizumab (on Day 1) and tazemetostat (on Days 1-21) of each 21-day cycle until unacceptable toxicities or disease progression.
arm group label: Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat
arm group type: Experimental
description: Relapsed/refractory DLBCL participants will receive atezolizumab and tazemetostat as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.
intervention type: Drug
intervention name: Atezolizumab
description: During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.
arm group label: Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab
arm group label: Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab
arm group label: Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab
arm group label: Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat
arm group label: Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat
other name: Tecentriq
intervention type: Drug
intervention name: Obinutuzumab
description: During safety evaluation stage, obinutuzumab will be administered as 1000 mg IV infusion. During expansion stage, obinutuzumab will be administered as either 1000 mg IV infusion or at dose decided from safety evaluation stage.
arm group label: Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab
arm group label: Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab
intervention type: Drug
intervention name: Tazemetostat
description: Tazemetostat 800 mg will be administered orally, twice daily, on Days 1 to 21.
arm group label: Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab
arm group label: Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat
arm group label: Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat
other name: EPZ6438
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: France
country: Germany
country: Italy
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Atezolizumab
mesh term: Obinutuzumab