<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/NCT03003520</url>
  </required_header>
  <id_info>
    <org_study_id>MEDI4736-DLBCL-001</org_study_id>
    <secondary_id>2015-005173-20</secondary_id>
    <nct_id>NCT03003520</nct_id>
  </id_info>
  <brief_title>A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma</brief_title>
  <official_title>A Phase 2, Open-label, Multicenter Study to Evaluate the Safety and Clinical Activity of Durvalumab in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP) or With Lenalidomide Plus R-CHOP (R2-CHOP) in Subjects With Previously Untreated, High-Risk Diffuse Large B-Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celgene</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 2, two-arm, open-label study is designed to evaluate the safety, clinical&#xD;
      activity, and predictive biomarkers of durvalumab in combination with R-CHOP or R2-CHOP,&#xD;
      followed by durvalumab consolidation therapy in previously untreated subjects with high-risk&#xD;
      diffuse large B-cell lymphoma (DLBCL). Induction treatment with R-CHOP (± lenalidomide) will&#xD;
      last for a total of up to 6 to 8 treatment cycles (21 day cycles), and the total time on&#xD;
      study treatment, including durvalumab consolidation, will last up to 12 months.&#xD;
&#xD;
      On 05-Sep-2017, the US FDA has issued a Partial Clinical Hold on this study resulting in the&#xD;
      discontinuation of enrollment into Arm B (Durvalumab + Lenalidomide + R-CHOP). After the US&#xD;
      FDA Partial Clinical Hold, new eligible participants have been enrolled in Arm A (Durvalumab&#xD;
      + R-CHOP).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is conducted in participants with previously untreated, high-risk diffuse&#xD;
      large B-cell lymphoma (DLBCL). Patients with high-risk DLBCL typically have insufficient&#xD;
      therapeutic outcomes. Therefore, the addition of novel agents to the currently used induction&#xD;
      therapy (R-CHOP) is a rational approach to improve therapeutic outcomes in this disease&#xD;
      setting.&#xD;
&#xD;
      Based on pre-clinical and clinical observations, it is hypothesized that durvalumab will have&#xD;
      activity in DLBCL because the PD 1/PD L1 pathway is involved in the pathophysiology of DLBCL.&#xD;
      In particular, the addition of durvalumab may augment the anti-tumor activity of R-CHOP&#xD;
      against high-risk DLBCL sub-types.&#xD;
&#xD;
      The safety of durvalumab has already been explored. However, as there is limited clinical&#xD;
      experience with durvalumab in DLBCL, the study is divided into two stages:&#xD;
&#xD;
        -  A Safety Run-in Stage to evaluate the safety of the treatment combinations until at&#xD;
           least 10 subjects are included in each of the two treatment arms&#xD;
&#xD;
        -  An Expansion Stage to analyze the clinical activity of the treatment combinations&#xD;
&#xD;
      Results posted following Primary Outcome Completion date are based on a database cut-off of&#xD;
      August 2, 2018.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 28, 2017</start_date>
  <completion_date type="Actual">April 24, 2022</completion_date>
  <primary_completion_date type="Actual">April 24, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Who Achieved a Complete Response (CR) at the End of Induction Therapy</measure>
    <time_frame>From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
    <description>The primary efficacy analysis evaluated the complete response rate (CRR) at the end of the induction therapy in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined as a complete metabolic response and radiographic evidence showing target nodes/nodal masses regressed to ≤ 1.5 cm in longest diameter, no new lesions, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis for the primary endpoint was rejected if the lower limit of the confidence interval for the complete response rate at the completion of the induction therapy in the efficacy evaluable population is above 55%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Responded During Induction and Continued Into Consolidation Therapy (Database Cutoff Date: 02-Aug-2018)</measure>
    <time_frame>From first dose of study drug to completion of at least one cycle in the Consolidation Period (Day 1 up to Week 52)</time_frame>
    <description>The percentage of participants who achieved a partial response (PR) or complete response (CR) at the end of Induction and continued into consolidation period in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined in outcome #1. PR was defined as a partial metabolic response and radiographic evidence showing ≥ 50% decrease in sum of perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites, no new lesions, spleen must have regressed &gt; 50% in length beyond normal, and residual bone marrow involvement improved from baseline. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis was rejected if the lower limit of the confidence interval for the rate of subjects who continue consolidation therapy out of all subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) CD8 T-Cell Density</measure>
    <time_frame>Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
    <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Total Percentage</measure>
    <time_frame>Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
    <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Percentage of Tumor Cells</measure>
    <time_frame>Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
    <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for the Interferon Gamma Score (IFNG-Score) From Ribonucleic Acid (RNA)-Sequencing Data</measure>
    <time_frame>Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
    <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Treatment Emergent Adverse Events (TEAE)</measure>
    <time_frame>From the date of the first dose of study drug to within 90 days after the last dose of durvalumab or 28 days after the last dose of any investigational product (IP) whichever is greater. (Up to approximately 72 weeks)</time_frame>
    <description>An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild (no limitation in activity or intervention); - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); - Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); - Grade 4 = Life-threatening; - Grade 5 = Death. Relation to IP is determined by the investigator.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Lymphoma, Large B-Cell, Diffuse</condition>
  <arm_group>
    <arm_group_label>DUR + R-CHOP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>On Day 1 of each 21-day cycle, participants received durvalumab 1125 mg intravenously (IV) followed by R-CHOP (IV rituximab 375 mg/m^2, doxorubicin 50 mg/m^2, vincristine 1.4 mg/m^2 (maximum dose of 2.0 mg total), and cyclophosphamide 750 mg/m^2); Participants also were administered daily oral or IV prednisone/prednisolone 100 mg from Day 1 to 5. Induction treatment continued for a total of 6-8 cycles.&#xD;
Participants who achieve a complete response or partial response continue with consolidation therapy treatment consisting of durvalumab monotherapy 1500 mg by IV on Day 1 of each 28-day cycle for up to a total of 12 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DUR + R2-CHOP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants start the study on durvalumab in combination with R-CHOP (as described in Arm DUR + R-CHOP). Based on their DLBCL Cell-of-Origin subtype (test typically done between cycles 1 and 2), participants with ABC subtype continue the study taking durvalumab in combination with R2-CHOP. On Day 1 of each 21-day cycle, participants received durvalumab 1125 mg intravenously (IV) followed by R-CHOP. Participants were also administered daily oral or IV prednisone/prednisolone 100 mg from Day 1 to 5. In addition, a daily oral lenalidomide 15 mg was administered from Day 1 to 14 of each 21-day cycle. Induction treatment continued for a total of 6-8 cycles.&#xD;
Participants who achieve a complete response or partial response continue with consolidation therapy treatment consisting of durvalumab monotherapy 1500 mg by IV on Day 1 of each 28-day cycle for up to a total of 12 months.&#xD;
Enrollment into Arm B was discontinued.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab was supplied in single use vials as a liquid solution containing 500 mg (nominal) of durvalumab at a concentration of 50 mg/mL to be infused by intravenous (IV) injection.&#xD;
Day 1 of each treatment cycle (Induction Period and Consolidation Period) started with the administration of IV durvalumab followed by a 2-hour observation period post infusion.</description>
    <arm_group_label>DUR + R-CHOP</arm_group_label>
    <arm_group_label>DUR + R2-CHOP</arm_group_label>
    <other_name>MEDI4736</other_name>
    <other_name>IMFINZI™</other_name>
    <other_name>DUR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Subsequent to durvalumab infusion, rituximab was administered by IV. Rituximab administration could be split over 2 consecutive days according to local clinical practice. Rapid infusion of rituximab was not allowed in this clinical study.</description>
    <arm_group_label>DUR + R-CHOP</arm_group_label>
    <arm_group_label>DUR + R2-CHOP</arm_group_label>
    <other_name>RITUXAN®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.</description>
    <arm_group_label>DUR + R-CHOP</arm_group_label>
    <arm_group_label>DUR + R2-CHOP</arm_group_label>
    <other_name>Adriamycin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.</description>
    <arm_group_label>DUR + R-CHOP</arm_group_label>
    <arm_group_label>DUR + R2-CHOP</arm_group_label>
    <other_name>leurocristine</other_name>
    <other_name>Oncovin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.</description>
    <arm_group_label>DUR + R-CHOP</arm_group_label>
    <arm_group_label>DUR + R2-CHOP</arm_group_label>
    <other_name>cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Prednisone was administered as an IV infusion or by mouth (PO) on Day 1, followed by PO administration on Days 2-5 of each cycle.&#xD;
Prednisone could be given prior to other drugs of the CHOP therapy. It was administered after lenalidomide dosing in the R2-CHOP treatment arm.</description>
    <arm_group_label>DUR + R-CHOP</arm_group_label>
    <arm_group_label>DUR + R2-CHOP</arm_group_label>
    <other_name>corticosteroid</other_name>
    <other_name>prednisolone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Lenalidomide was administered orally in capsule form on Days 1-14 of the DUR+R2-CHOP treatment arm only.</description>
    <arm_group_label>DUR + R2-CHOP</arm_group_label>
    <other_name>Revlimid®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. CD20+Diffuse Large B-Cell Lymphoma.&#xD;
&#xD;
          2. Ann Arbor stage 3 or 4 or stage 2 with bulky disease&#xD;
&#xD;
          3. High or high-intermediate disease risk.&#xD;
&#xD;
          4. No prior anti-lymphoma treatment.&#xD;
&#xD;
          5. Subject is willing and able to undergo biopsy.&#xD;
&#xD;
          6. Investigator considers R-CHOP immunochemotherapy appropriate.&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.&#xD;
&#xD;
          8. Adequate hematology laboratory results (absolute neutrophil count ≥ 1.5 * 10^9/L,&#xD;
             platelet count ≥ 75 * 10^9/L, hemoglobin ≥ 10.0 g/dL).&#xD;
&#xD;
          9. Adequate biochemistry laboratory results (aspartate aminotransferase (AST/SGOT) and&#xD;
             alanine aminotransferase (ALT/SGPT) ≤ 3.0 * upper limit of normal; bilirubin ≤ 2.0&#xD;
             mg/dL; creatinine clearance of ≥ 40 mL/min).&#xD;
&#xD;
         10. Bi-dimensionally measurable disease (&gt; 2.0 cm).&#xD;
&#xD;
         11. Subject is using effective contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of lymphoma other than Diffuse Large B-Cell Lymphoma.&#xD;
&#xD;
          2. Composite lymphoma or transformed lymphoma.&#xD;
&#xD;
          3. Primary or secondary Central Nervous System involvement by lymphoma.&#xD;
&#xD;
          4. Seropositive or active viral infection with hepatitis B virus, human immunodeficiency&#xD;
             virus or hepatitis C virus.&#xD;
&#xD;
          5. History of other malignancies, unless disease-free for ≥ 5 years.&#xD;
&#xD;
          6. Left ventricular ejection fraction &lt; 50%.&#xD;
&#xD;
          7. Peripheral neuropathy ≥ Grade 2.&#xD;
&#xD;
          8. Prior use of lenalidomide, or monoclonal antibodies against CTLA-4, PD-1, or PD-L1.&#xD;
&#xD;
          9. High risk of developing thromboembolic events, who are unwilling to take venous&#xD;
             thromboembolism prophylaxis.&#xD;
&#xD;
         10. Active or prior documented autoimmune or inflammatory disorders within the past 3&#xD;
             years.&#xD;
&#xD;
         11. Current or prior use of immunosuppressive medication within 28 days before start of&#xD;
             treatment.&#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>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkview Research Center</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid Ohio Oncology Hematology Inc</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Cancer Institute</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innsbruck Medical University Department of Internal Medicine</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Landeskrankenhaus Salzburg</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 101</name>
      <address>
        <city>Vienna</city>
        <zip>1190</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of Vienna Internalmedicine 1, Hematology</name>
      <address>
        <city>Vienna</city>
        <zip>1190</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hanusch Krankenhaus</name>
      <address>
        <city>Wien</city>
        <zip>1140</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aarhus Sygehus</name>
      <address>
        <city>Arhus C</city>
        <zip>DK-8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet, Kobenhavns Universitet - Centre for Clinical Intervention Research - The Copenhagen</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odense Universitetshospital</name>
      <address>
        <city>Odense C</city>
        <zip>DK5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>(North Estonia Medical Centre) - Onkoloogia-ja Hematoloogiakliinik</name>
      <address>
        <city>Tallinn</city>
        <zip>13419</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tartu University Hospital</name>
      <address>
        <city>Tartu</city>
        <zip>51014</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Birmingham</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine</name>
      <address>
        <city>Oxford</city>
        <zip>0X3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Denmark</country>
    <country>Estonia</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czechia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Slovakia</country>
  </removed_countries>
  <link>
    <url>https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html</url>
    <description>BMS Clinical Trial Information</description>
  </link>
  <link>
    <url>https://www.bmsstudyconnect.com/s/US/English/USenHome</url>
    <description>BMS Clinical Trial Patient Recruiting</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <results_first_submitted>August 2, 2019</results_first_submitted>
  <results_first_submitted_qc>September 12, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">September 16, 2019</results_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lymphoma</keyword>
  <keyword>Diffuse-large B-Cell Lymphoma</keyword>
  <keyword>Durvalumab</keyword>
  <keyword>Anti-PD-L1 Antibody</keyword>
  <keyword>MEDI4736</keyword>
  <keyword>Immune Checkpoint</keyword>
  <keyword>Rituximab</keyword>
  <keyword>Cyclophosphamide</keyword>
  <keyword>Doxorubicin</keyword>
  <keyword>Vincristine</keyword>
  <keyword>Prednisone/Prednisolone</keyword>
  <keyword>Lenalidomide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell</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>Prednisone</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT03003520/Prot_SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>DUR + R-CHOP</title>
          <description>Participants receive Induction Therapy (21-day cycles): Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5).&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
        </group>
        <group group_id="P2">
          <title>DUR + R2-CHOP</title>
          <description>Participants receive Induction Therapy (21-day cycles): Cycle 1 - induction therapy of durvalumab in combination with R-CHOP (as described in DUR + R-CHOP arm). Starting at cycle 2 - Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide 15 mg from Day 1 to 14) from the cycle following COO determination until end of induction therapy (Cycle 6 or Cycle 8) or starting Cycle 1 if ABC subtype is identified prior to C1D1.&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Induction Treatment</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Consolidation Treatment</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other reasons</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety population</population>
      <group_list>
        <group group_id="B1">
          <title>DUR + R-CHOP</title>
          <description>Participants receive Induction Therapy (21-day cycles): Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5).&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
        </group>
        <group group_id="B2">
          <title>DUR + R2-CHOP</title>
          <description>Participants receive Induction Therapy (21-day cycles): Cycle 1 - induction therapy of durvalumab in combination with R-CHOP (as described in DUR + R-CHOP arm). Starting at cycle 2 - Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide 15 mg from Day 1 to 14) from the cycle following COO determination until end of induction therapy (Cycle 6 or Cycle 8) or starting Cycle 1 if ABC subtype is identified prior to C1D1.&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="43"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="46"/>
          </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="61.1" spread="12.77"/>
                    <measurement group_id="B2" value="67.7" spread="8.62"/>
                    <measurement group_id="B3" value="61.5" spread="12.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>&lt;65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="22"/>
                  </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="17"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Colected or Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG)</title>
          <description>ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. - 0 = Fully Active (most favorable status); - 1 = Restricted activity but ambulatory; - 2 = Ambulatory but unable to carry out work activities; - 3 = Limited Self-Care; - 4 = Completely Disabled, No self-care (least favorable status)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0 = Fully Active</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1 = Restricted activity but ambulatory</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2 = Ambulatory but unable to work</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3 = Limited Self-Care</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4 = Completely Disabled, No self-care</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ann Arbor Stage at Diagnosis</title>
          <description>The criteria for Clinical Stage (Ann Arbor staging) are as below: - I: involvement of a single nodal region. - II: involvement of 2 or more lymph node regions on the same side of the diaphragm. - III: involvement of lymph node regions on both sides of the diaphragm. - IV: disseminated involvement of 1 or more extra-lymphatic sites with or without associated lymph node involvement.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Stage I</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage IV</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Presence of Bulky Disease at Baseline</title>
          <description>Bulky disease refers to the size of the tumor. - Yes = tumor diameter &gt;= 7.0 cm. - No = tumor diameter &lt; 7.0 cm.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>International Prognostic Index (IPSS) Score</title>
          <description>The IPI assesses risk of central nervous system disease according to the following scale: - 0-1: Low risk - 2: Low-Intermediate risk - 3: High-Intermediate risk - 4-5: High risk</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0-1: Low risk</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2: Low-Intermediate risk</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3: High-Intermediate risk</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4-5: High risk</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Achieved a Complete Response (CR) at the End of Induction Therapy</title>
        <description>The primary efficacy analysis evaluated the complete response rate (CRR) at the end of the induction therapy in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined as a complete metabolic response and radiographic evidence showing target nodes/nodal masses regressed to ≤ 1.5 cm in longest diameter, no new lesions, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis for the primary endpoint was rejected if the lower limit of the confidence interval for the complete response rate at the completion of the induction therapy in the efficacy evaluable population is above 55%.</description>
        <time_frame>From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
        <population>Efficacy Evaluable Population includes participants who completed at least one cycle of their assigned treatment, had a baseline assessment by CT scan and at least one post baseline tumor response assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>DUR + R-CHOP</title>
            <description>Participants receive Induction Therapy (21-day cycles): Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5).&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
          </group>
          <group group_id="O2">
            <title>DUR + R2-CHOP</title>
            <description>Participants receive Induction Therapy (21-day cycles): Cycle 1 - induction therapy of durvalumab in combination with R-CHOP (as described in DUR + R-CHOP arm). Starting at cycle 2 - Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide 15 mg from Day 1 to 14) from the cycle following COO determination until end of induction therapy (Cycle 6 or Cycle 8) or starting Cycle 1 if ABC subtype is identified prior to C1D1.&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved a Complete Response (CR) at the End of Induction Therapy</title>
          <description>The primary efficacy analysis evaluated the complete response rate (CRR) at the end of the induction therapy in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined as a complete metabolic response and radiographic evidence showing target nodes/nodal masses regressed to ≤ 1.5 cm in longest diameter, no new lesions, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis for the primary endpoint was rejected if the lower limit of the confidence interval for the complete response rate at the completion of the induction therapy in the efficacy evaluable population is above 55%.</description>
          <population>Efficacy Evaluable Population includes participants who completed at least one cycle of their assigned treatment, had a baseline assessment by CT scan and at least one post baseline tumor response assessment.</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="37"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.1" lower_limit="36.9" upper_limit="70.5"/>
                    <measurement group_id="O2" value="66.7" lower_limit="9.4" upper_limit="99.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Responded During Induction and Continued Into Consolidation Therapy (Database Cutoff Date: 02-Aug-2018)</title>
        <description>The percentage of participants who achieved a partial response (PR) or complete response (CR) at the end of Induction and continued into consolidation period in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined in outcome #1. PR was defined as a partial metabolic response and radiographic evidence showing ≥ 50% decrease in sum of perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites, no new lesions, spleen must have regressed &gt; 50% in length beyond normal, and residual bone marrow involvement improved from baseline. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis was rejected if the lower limit of the confidence interval for the rate of subjects who continue consolidation therapy out of all subjects.</description>
        <time_frame>From first dose of study drug to completion of at least one cycle in the Consolidation Period (Day 1 up to Week 52)</time_frame>
        <population>Efficacy Evaluable Population includes participants who completed at least one cycle of their assigned treatment, had a baseline assessment by CT scan and at least one post baseline tumor response assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>DUR + R-CHOP</title>
            <description>Participants receive Induction Therapy (21-day cycles): Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5).&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
          </group>
          <group group_id="O2">
            <title>DUR + R2-CHOP</title>
            <description>Participants receive Induction Therapy (21-day cycles): Cycle 1 - induction therapy of durvalumab in combination with R-CHOP (as described in DUR + R-CHOP arm). Starting at cycle 2 - Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide 15 mg from Day 1 to 14) from the cycle following COO determination until end of induction therapy (Cycle 6 or Cycle 8) or starting Cycle 1 if ABC subtype is identified prior to C1D1.&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Responded During Induction and Continued Into Consolidation Therapy (Database Cutoff Date: 02-Aug-2018)</title>
          <description>The percentage of participants who achieved a partial response (PR) or complete response (CR) at the end of Induction and continued into consolidation period in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined in outcome #1. PR was defined as a partial metabolic response and radiographic evidence showing ≥ 50% decrease in sum of perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites, no new lesions, spleen must have regressed &gt; 50% in length beyond normal, and residual bone marrow involvement improved from baseline. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis was rejected if the lower limit of the confidence interval for the rate of subjects who continue consolidation therapy out of all subjects.</description>
          <population>Efficacy Evaluable Population includes participants who completed at least one cycle of their assigned treatment, had a baseline assessment by CT scan and at least one post baseline tumor response assessment.</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="37"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.6" lower_limit="50.2" upper_limit="82.0"/>
                    <measurement group_id="O2" value="66.7" lower_limit="9.4" upper_limit="99.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) CD8 T-Cell Density</title>
        <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
        <time_frame>Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
        <population>The RNA Biomarker Analysis Set included all Efficacy Evaluable participants who have RNA Sequencing analysis performed on a biopsy sample and collected from the participant before treatment on the protocol. Population included participants who received durvalumab. Samples with whole transcriptome data of low quality were excluded from the set.</population>
        <group_list>
          <group group_id="O1">
            <title>High Group for CD8 Density</title>
            <description>Participants had IHC analysis performed on a biopsy sample collected before treatment on this protocol. The result of their CD8 density evaluation was above threshold,defined as the median of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods. Participants with values above threshold were predicted to be responders.</description>
          </group>
          <group group_id="O2">
            <title>Low Group for CD8 Density</title>
            <description>Participants had IHC analysis performed on a biopsy sample collected before treatment on this protocol. The result of their CD8 density evaluation was below threshold,defined as the median of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods. Participants with values below threshold were predicted to be non-responders.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) CD8 T-Cell Density</title>
          <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
          <population>The RNA Biomarker Analysis Set included all Efficacy Evaluable participants who have RNA Sequencing analysis performed on a biopsy sample and collected from the participant before treatment on the protocol. Population included participants who received durvalumab. Samples with whole transcriptome data of low quality were excluded from the set.</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="15"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67"/>
                    <measurement group_id="O2" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <p_value_desc>Significance defined as 0.05.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The Area Under the Receiver Operator Characteristic Curve (AUC-ROC) is the estimated parameter. Responders were compared to non-responders by ranking them according to their CD8 density.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.872</p_value>
            <p_value_desc>Significance defined as 0.05.</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>AUC-ROC</param_type>
            <param_value>0.477</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Total Percentage</title>
        <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
        <time_frame>Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
        <population>The RNA Biomarker Analysis Set included all Efficacy Evaluable participants who have RNA Sequencing analysis performed on a biopsy sample and collected from the participant before treatment on the protocol. Population included participants who received durvalumab. Samples with whole transcriptome data of low quality were excluded from the set.</population>
        <group_list>
          <group group_id="O1">
            <title>High Group for PDL1 % of Total Cells</title>
            <description>Participants had IHC analysis performed on a biopsy sample collected before treatment on this protocol. The result of their PDL1 % of total cell evaluation was above threshold,defined as the median of 13.8% found in commercial DLBCL samples using matched analytical methods. Participants with values above threshold were predicted to be responders.</description>
          </group>
          <group group_id="O2">
            <title>Low Group for PDL1 % of Total Cells</title>
            <description>Participants had IHC analysis performed on a biopsy sample collected before treatment on this protocol. The result of their PDL1 % of total cell evaluation was below threshold,defined as the median of 13.8% found in commercial DLBCL samples using matched analytical methods. Participants with values below threshold were predicted to be non-responders.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Total Percentage</title>
          <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
          <population>The RNA Biomarker Analysis Set included all Efficacy Evaluable participants who have RNA Sequencing analysis performed on a biopsy sample and collected from the participant before treatment on the protocol. Population included participants who received durvalumab. Samples with whole transcriptome data of low quality were excluded from the set.</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="20"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0403</p_value>
            <p_value_desc>Significance defined as 0.05.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The Area Under the Receiver Operator Characteristic Curve (AUC-ROC) is the estimated parameter. Responders were compared to non-responders by ranking them according to their PDL1 % of total cells.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.523</p_value>
            <p_value_desc>Significance defined as 0.05.</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>AUC-ROC</param_type>
            <param_value>0.583</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Percentage of Tumor Cells</title>
        <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
        <time_frame>Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
        <population>The RNA Biomarker Analysis Set included all Efficacy Evaluable participants who have RNA Sequencing analysis performed on a biopsy sample and collected from the participant before treatment on the protocol. Population included participants who received durvalumab. Samples with whole transcriptome data of low quality were excluded from the set.</population>
        <group_list>
          <group group_id="O1">
            <title>High Group for PDL1 % of Tumor Cells</title>
            <description>Participants had IHC analysis performed on a biopsy sample collected before treatment on this protocol. The result of their PD-1 % of tumor cell evaluation was above threshold,defined as the median of 6.2% found in commercial DLBCL samples using matched analytical methods. Participants with values above threshold were predicted to be responders.</description>
          </group>
          <group group_id="O2">
            <title>Low Group for PDL1 % of Tumor Cells</title>
            <description>Participants had IHC analysis performed on a biopsy sample collected before treatment on this protocol. The result of their PDL1 % of tumor cell evaluation was below threshold,defined as the median of 6.2% found in commercial DLBCL samples using matched analytical methods. Participants with values below threshold were predicted to be non-responders.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Percentage of Tumor Cells</title>
          <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
          <population>The RNA Biomarker Analysis Set included all Efficacy Evaluable participants who have RNA Sequencing analysis performed on a biopsy sample and collected from the participant before treatment on the protocol. Population included participants who received durvalumab. Samples with whole transcriptome data of low quality were excluded from the set.</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="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                    <measurement group_id="O2" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <p_value_desc>Significance defined as 0.05.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The Area Under the Receiver Operator Characteristic Curve (AUC-ROC) is the estimated parameter. Responders were compared to non-responders by ranking them according to their PDL1 % of tumor cells.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.557</p_value>
            <p_value_desc>Significance defined as 0.05.</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>AUC-ROC</param_type>
            <param_value>0.583</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for the Interferon Gamma Score (IFNG-Score) From Ribonucleic Acid (RNA)-Sequencing Data</title>
        <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
        <time_frame>Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).</time_frame>
        <population>The RNA Biomarker Analysis Set included all Efficacy Evaluable participants who have RNA Sequencing analysis performed on a biopsy sample and collected from the participant before treatment on the protocol. Population included participants who received durvalumab. Samples with whole transcriptome data of low quality were excluded from the set.</population>
        <group_list>
          <group group_id="O1">
            <title>High Group for RNA IFN Gamma Score</title>
            <description>Participants had RNA IFN Gamma Score calculated based on a biopsy sample collected before treatment on this protocol. The result of their RNA IFN Gamma Score was above threshold,defined as the median of 3.28 found in commercial DLBCL samples using matched analytical methods. Participants with values above threshold were predicted to be responders.</description>
          </group>
          <group group_id="O2">
            <title>Low Group for RNA IFN Gamma Score</title>
            <description>Participants had RNA IFN Gamma Score calculated based on a biopsy sample collected before treatment on this protocol. The result of their RNA IFN Gamma Score was below threshold,defined as the median of 3.28 found in commercial DLBCL samples using matched analytical methods. Participants with values below threshold were predicted to be non-responders.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for the Interferon Gamma Score (IFNG-Score) From Ribonucleic Acid (RNA)-Sequencing Data</title>
          <description>Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.</description>
          <population>The RNA Biomarker Analysis Set included all Efficacy Evaluable participants who have RNA Sequencing analysis performed on a biopsy sample and collected from the participant before treatment on the protocol. Population included participants who received durvalumab. Samples with whole transcriptome data of low quality were excluded from the set.</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="7"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43"/>
                    <measurement group_id="O2" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.662</p_value>
            <p_value_desc>Significance defined as 0.05.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The Area Under the Receiver Operator Characteristic Curve (AUC-ROC) is the estimated parameter. Responders were compared to non-responders by ranking them according to their IFNG-Score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.399</p_value>
            <p_value_desc>Significance defined as 0.05.</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>AUC-ROC</param_type>
            <param_value>0.6</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Treatment Emergent Adverse Events (TEAE)</title>
        <description>An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild (no limitation in activity or intervention); - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); - Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); - Grade 4 = Life-threatening; - Grade 5 = Death. Relation to IP is determined by the investigator.</description>
        <time_frame>From the date of the first dose of study drug to within 90 days after the last dose of durvalumab or 28 days after the last dose of any investigational product (IP) whichever is greater. (Up to approximately 72 weeks)</time_frame>
        <population>Safety Population, which consists of all participants who received at least 1 dose of the study medications. Participants were analyzed in the arm of the actual treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>DUR + R-CHOP</title>
            <description>Participants receive Induction Therapy (21-day cycles): Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5).&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
          </group>
          <group group_id="O2">
            <title>DUR + R2-CHOP</title>
            <description>Participants receive Induction Therapy (21-day cycles): Cycle 1 - induction therapy of durvalumab in combination with R-CHOP (as described in DUR + R-CHOP arm). Starting at cycle 2 - Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide 15 mg from Day 1 to 14) from the cycle following COO determination until end of induction therapy (Cycle 6 or Cycle 8) or starting Cycle 1 if ABC subtype is identified prior to C1D1.&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Treatment Emergent Adverse Events (TEAE)</title>
          <description>An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild (no limitation in activity or intervention); - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); - Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); - Grade 4 = Life-threatening; - Grade 5 = Death. Relation to IP is determined by the investigator.</description>
          <population>Safety Population, which consists of all participants who received at least 1 dose of the study medications. Participants were analyzed in the arm of the actual treatment received.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>&gt;= 1 Treatment-emergent adverse event (TEAE)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE related to durvalumab</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE related to R-CHOP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE related to lenalidomide</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE related to durvalumab or any other IP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE severity grade 3-4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE severity grade 3-4 related to durvalumab</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE severity grade 3-4 related to R-CHOP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE severity grade 3-4 related to lenalidomid</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE severity grade 3-4 related to any IP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE severity grade 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 TEAE severity grade 5 related to any IP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 serious TEAE</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 serious TEAE related to durvalumab</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 serious TEAE related to R-CHOP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 serious TEAE related to lenalidomide</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 serious TEAE related to any IP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to discontinuation of durvalumab</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to discontinuation of R-CHOP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to discontinuation of lenalidomide</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to discontinuation of any IP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to interruption of durvalumab</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to interruption of R-CHOP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to interruption of lenalidomide</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to interruption of any IP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to infusion interruption of durvalumab</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to dose reduction of vincristine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=1 leading to dose reduction of lenalidomide</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs and SAEs were assessed from first dose to 90 days after the last dose of durvalumab or 28 days after the last dose of any other IP, whichever is later (up to approximately 72 weeks) and up to 5 years after enrollment (C1D1) of the last participant to receive lenalidomide (up to approximately 5 years). All-Cause Mortality was assessed in participants from their first dose to their study completion (up to approximately 5 years).</time_frame>
      <desc>Participants treated with lenalidomide during any stage of the study will be continued to be followed for Second Primary Malignancies (SPM) for up to 5 years after enrollment (C1D1) of the last participant to receive lenalidomide as part of their study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>DUR + R-CHOP</title>
          <description>Participants receive Induction Therapy (21-day cycles): Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5).&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
        </group>
        <group group_id="E2">
          <title>DUR + R2-CHOP</title>
          <description>Participants receive Induction Therapy (21-day cycles): Cycle 1 - induction therapy of durvalumab in combination with R-CHOP (as described in DUR + R-CHOP arm). Starting at cycle 2 - Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide 15 mg from Day 1 to 14) from the cycle following COO determination until end of induction therapy (Cycle 6 or Cycle 8) or starting Cycle 1 if ABC subtype is identified prior to C1D1.&#xD;
Participants then receive Consolidation Therapy (28-day cycles): Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1 of induction therapy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>22.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune hepatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemophagocytic lymphohistiocytosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Meningitis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Perirectal abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Viral diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </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" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Spinal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Clear cell renal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diffuse large B-cell lymphoma recurrent</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lymphoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Seborrhoeic dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Venous thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>22.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoacusis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Spinal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Histiocytic necrotising lymphadenitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Sensory disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Taste disorder</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Generalised erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </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>Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>After the US FDA Partial Clinical Hold, enrollment of new participants into Arm B was discontinued. If receiving clinical benefit at the discretion of the Investigator, participants could continue treatment in Arm B after being reconsented. Any newly enrolled participant with DLBCL of ABC COO subtype after the US FDA Partial Clinical Hold could continue induction therapy on Arm A after Cycle 1.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Bristol-Myers Squibb Study Director</name_or_title>
      <organization>Bristol-Myers Squibb</organization>
      <phone>Please email</phone>
      <email>Clinical.Trials@bms.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/NCT03003520
org study id: MEDI4736-DLBCL-001
secondary id: 2015-005173-20
nct id: NCT03003520
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This Phase 2, two-arm, open-label study is designed to evaluate the safety, clinical
      activity, and predictive biomarkers of durvalumab in combination with R-CHOP or R2-CHOP,
      followed by durvalumab consolidation therapy in previously untreated subjects with high-risk
      diffuse large B-cell lymphoma (DLBCL). Induction treatment with R-CHOP (± lenalidomide) will
      last for a total of up to 6 to 8 treatment cycles (21 day cycles), and the total time on
      study treatment, including durvalumab consolidation, will last up to 12 months.

      On 05-Sep-2017, the US FDA has issued a Partial Clinical Hold on this study resulting in the
      discontinuation of enrollment into Arm B (Durvalumab + Lenalidomide + R-CHOP). After the US
      FDA Partial Clinical Hold, new eligible participants have been enrolled in Arm A (Durvalumab
      + R-CHOP).
This research study is conducted in participants with previously untreated, high-risk diffuse
      large B-cell lymphoma (DLBCL). Patients with high-risk DLBCL typically have insufficient
      therapeutic outcomes. Therefore, the addition of novel agents to the currently used induction
      therapy (R-CHOP) is a rational approach to improve therapeutic outcomes in this disease
      setting.

      Based on pre-clinical and clinical observations, it is hypothesized that durvalumab will have
      activity in DLBCL because the PD 1/PD L1 pathway is involved in the pathophysiology of DLBCL.
      In particular, the addition of durvalumab may augment the anti-tumor activity of R-CHOP
      against high-risk DLBCL sub-types.

      The safety of durvalumab has already been explored. However, as there is limited clinical
      experience with durvalumab in DLBCL, the study is divided into two stages:

        -  A Safety Run-in Stage to evaluate the safety of the treatment combinations until at
           least 10 subjects are included in each of the two treatment arms

        -  An Expansion Stage to analyze the clinical activity of the treatment combinations

      Results posted following Primary Outcome Completion date are based on a database cut-off of
      August 2, 2018.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Who Achieved a Complete Response (CR) at the End of Induction Therapy
time frame: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
description: The primary efficacy analysis evaluated the complete response rate (CRR) at the end of the induction therapy in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined as a complete metabolic response and radiographic evidence showing target nodes/nodal masses regressed to ≤ 1.5 cm in longest diameter, no new lesions, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis for the primary endpoint was rejected if the lower limit of the confidence interval for the complete response rate at the completion of the induction therapy in the efficacy evaluable population is above 55%.
measure: Percentage of Participants Who Responded During Induction and Continued Into Consolidation Therapy (Database Cutoff Date: 02-Aug-2018)
time frame: From first dose of study drug to completion of at least one cycle in the Consolidation Period (Day 1 up to Week 52)
description: The percentage of participants who achieved a partial response (PR) or complete response (CR) at the end of Induction and continued into consolidation period in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined in outcome #1. PR was defined as a partial metabolic response and radiographic evidence showing ≥ 50% decrease in sum of perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites, no new lesions, spleen must have regressed > 50% in length beyond normal, and residual bone marrow involvement improved from baseline. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis was rejected if the lower limit of the confidence interval for the rate of subjects who continue consolidation therapy out of all subjects.
measure: Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) CD8 T-Cell Density
time frame: Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
description: Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.
measure: Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Total Percentage
time frame: Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
description: Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.
measure: Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Percentage of Tumor Cells
time frame: Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
description: Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.
measure: Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for the Interferon Gamma Score (IFNG-Score) From Ribonucleic Acid (RNA)-Sequencing Data
time frame: Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
description: Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome.
measure: Participants With Treatment Emergent Adverse Events (TEAE)
time frame: From the date of the first dose of study drug to within 90 days after the last dose of durvalumab or 28 days after the last dose of any investigational product (IP) whichever is greater. (Up to approximately 72 weeks)
description: An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild (no limitation in activity or intervention); - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); - Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); - Grade 4 = Life-threatening; - Grade 5 = Death. Relation to IP is determined by the investigator.
arm group label: DUR + R-CHOP
arm group type: Experimental
description: On Day 1 of each 21-day cycle, participants received durvalumab 1125 mg intravenously (IV) followed by R-CHOP (IV rituximab 375 mg/m^2, doxorubicin 50 mg/m^2, vincristine 1.4 mg/m^2 (maximum dose of 2.0 mg total), and cyclophosphamide 750 mg/m^2); Participants also were administered daily oral or IV prednisone/prednisolone 100 mg from Day 1 to 5. Induction treatment continued for a total of 6-8 cycles.
Participants who achieve a complete response or partial response continue with consolidation therapy treatment consisting of durvalumab monotherapy 1500 mg by IV on Day 1 of each 28-day cycle for up to a total of 12 months.
arm group label: DUR + R2-CHOP
arm group type: Experimental
description: Participants start the study on durvalumab in combination with R-CHOP (as described in Arm DUR + R-CHOP). Based on their DLBCL Cell-of-Origin subtype (test typically done between cycles 1 and 2), participants with ABC subtype continue the study taking durvalumab in combination with R2-CHOP. On Day 1 of each 21-day cycle, participants received durvalumab 1125 mg intravenously (IV) followed by R-CHOP. Participants were also administered daily oral or IV prednisone/prednisolone 100 mg from Day 1 to 5. In addition, a daily oral lenalidomide 15 mg was administered from Day 1 to 14 of each 21-day cycle. Induction treatment continued for a total of 6-8 cycles.
Participants who achieve a complete response or partial response continue with consolidation therapy treatment consisting of durvalumab monotherapy 1500 mg by IV on Day 1 of each 28-day cycle for up to a total of 12 months.
Enrollment into Arm B was discontinued.
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab was supplied in single use vials as a liquid solution containing 500 mg (nominal) of durvalumab at a concentration of 50 mg/mL to be infused by intravenous (IV) injection.
Day 1 of each treatment cycle (Induction Period and Consolidation Period) started with the administration of IV durvalumab followed by a 2-hour observation period post infusion.
arm group label: DUR + R-CHOP
arm group label: DUR + R2-CHOP
other name: MEDI4736
other name: IMFINZI™
other name: DUR
intervention type: Drug
intervention name: Rituximab
description: Subsequent to durvalumab infusion, rituximab was administered by IV. Rituximab administration could be split over 2 consecutive days according to local clinical practice. Rapid infusion of rituximab was not allowed in this clinical study.
arm group label: DUR + R-CHOP
arm group label: DUR + R2-CHOP
other name: RITUXAN®
intervention type: Drug
intervention name: Doxorubicin
description: A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
arm group label: DUR + R-CHOP
arm group label: DUR + R2-CHOP
other name: Adriamycin
intervention type: Drug
intervention name: Vincristine
description: A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
arm group label: DUR + R-CHOP
arm group label: DUR + R2-CHOP
other name: leurocristine
other name: Oncovin
intervention type: Drug
intervention name: Cyclophosphamide
description: A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
arm group label: DUR + R-CHOP
arm group label: DUR + R2-CHOP
other name: cytophosphane
other name: Cytoxan
intervention type: Drug
intervention name: Prednisone
description: Prednisone was administered as an IV infusion or by mouth (PO) on Day 1, followed by PO administration on Days 2-5 of each cycle.
Prednisone could be given prior to other drugs of the CHOP therapy. It was administered after lenalidomide dosing in the R2-CHOP treatment arm.
arm group label: DUR + R-CHOP
arm group label: DUR + R2-CHOP
other name: corticosteroid
other name: prednisolone
intervention type: Drug
intervention name: Lenalidomide
description: Lenalidomide was administered orally in capsule form on Days 1-14 of the DUR+R2-CHOP treatment arm only.
arm group label: DUR + R2-CHOP
other name: Revlimid®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Denmark
country: Estonia
country: United Kingdom
country: United States
country: Czechia
country: France
country: Germany
country: Poland
country: Portugal
country: Slovakia
url: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
description: BMS Clinical Trial Information
url: https://www.bmsstudyconnect.com/s/US/English/USenHome
description: BMS Clinical Trial Patient Recruiting
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Prednisone
mesh term: Prednisolone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Doxorubicin
mesh term: Vincristine
mesh term: Lenalidomide
mesh term: Durvalumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: After the US FDA Partial Clinical Hold, enrollment of new participants into Arm B was discontinued. If receiving clinical benefit at the discretion of the Investigator, participants could continue treatment in Arm B after being reconsented. Any newly enrolled participant with DLBCL of ABC COO subtype after the US FDA Partial Clinical Hold could continue induction therapy on Arm A after Cycle 1.
point of contact: 