<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/NCT03836261</url>
  </required_header>
  <id_info>
    <org_study_id>ACE-CL-311</org_study_id>
    <secondary_id>D8221C00001</secondary_id>
    <secondary_id>2018-002443-28</secondary_id>
    <nct_id>NCT03836261</nct_id>
    <nct_alias>NCT05211856</nct_alias>
  </id_info>
  <brief_title>Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL</brief_title>
  <official_title>A Randomized, Multicenter, Open-Label, Phase 3 Study to Compare the Efficacy and Safety of Acalabrutinib (ACP-196) in Combination With Venetoclax With and Without Obinutuzumab Compared to Investigator's Choice of Chemoimmunotherapy in Subjects With Previously Untreated Chronic Lymphocytic Leukemia Without Del(17p) or TP53 Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Acerta Pharma BV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Acerta Pharma BV</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>
      The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in&#xD;
      combination with venetoclax and acalabrutinib in combination with venetoclax with and without&#xD;
      obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized, global, multicenter, open-label, Phase 3 study will evaluate the efficacy&#xD;
      and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in subjects with previously&#xD;
      untreated CLL without del(17p) or TP53. Subjects will be randomized in a 1:1:1 ratio into 3&#xD;
      arms through a block stratified randomization procedure.&#xD;
&#xD;
      The study includes screening (35 days), treatment (from randomization until study drug&#xD;
      discontinuation) and follow-up phase.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 25, 2019</start_date>
  <completion_date type="Anticipated">January 6, 2027</completion_date>
  <primary_completion_date type="Anticipated">January 6, 2027</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS</measure>
    <time_frame>6 years</time_frame>
    <description>Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS</measure>
    <time_frame>6 years</time_frame>
    <description>PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared with FCR or BR (Arm C): PFS defined the same as above per investigator assessment.</measure>
    <time_frame>6 years</time_frame>
    <description>PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">780</enrollment>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>Acalabrutinib, Venetoclax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acalabrutinib in combination with Venetoclax</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acalabrutinib, Venetoclax, Obinutuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acalabrutinib in combination with Venetoclax with or without Obinutuzumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chemoimmunotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Chemoimmunotherapy&#xD;
FCR: Fludarabine, Cyclophosphamide and Rituximab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acalabrutinib</intervention_name>
    <description>Acalabrutinib,</description>
    <arm_group_label>Acalabrutinib, Venetoclax</arm_group_label>
    <arm_group_label>Acalabrutinib, Venetoclax, Obinutuzumab</arm_group_label>
    <other_name>Calquence (acalabrutinib)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>Venetoclax</description>
    <arm_group_label>Acalabrutinib, Venetoclax</arm_group_label>
    <arm_group_label>Acalabrutinib, Venetoclax, Obinutuzumab</arm_group_label>
    <other_name>Venclyxto, Venclexta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chemoimmunotherapy</intervention_name>
    <description>fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)</description>
    <arm_group_label>Chemoimmunotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Obinutuzumab</intervention_name>
    <description>Obinutuzumab</description>
    <arm_group_label>Acalabrutinib, Venetoclax, Obinutuzumab</arm_group_label>
    <other_name>Gazyva, Gazyvaro</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women ≥18 years of age.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.&#xD;
&#xD;
          -  Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018)&#xD;
&#xD;
          -  Active disease per IWCLL 2018 criteria that requires treatment.&#xD;
&#xD;
          -  Participants must use highly effective birth control throughout the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any prior CLL-specific therapies.&#xD;
&#xD;
          -  Detected del(17p) or TP53 mutation.&#xD;
&#xD;
          -  Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (e.g., Richter's&#xD;
             transformation, prolymphocytic leukemia [PLL], or diffuse large B cell lymphoma&#xD;
             [DLBCL]), or central nervous system (CNS) involvement by leukemia.&#xD;
&#xD;
          -  History of confirmed progressive multifocal leukoencephalopathy (PML).&#xD;
&#xD;
          -  Received any investigational drug within 30 days before first dose of study drug.&#xD;
&#xD;
          -  Major surgical procedure within 30 days before the first dose of study drug.&#xD;
&#xD;
          -  Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart&#xD;
             failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4&#xD;
             cardiac disease. Note: Subjects with controlled, asymptomatic atrial fibrillation are&#xD;
             allowed to enroll on study.&#xD;
&#xD;
          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or&#xD;
             resection of the stomach, or extensive small bowel resection that is likely to affect&#xD;
             absorption, symptomatic inflammatory bowel disease, or partial or complete bowel&#xD;
             obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.&#xD;
&#xD;
          -  Received a live virus vaccination within 28 days of first dose of study drug.&#xD;
&#xD;
          -  Known history of infection with human immunodeficiency virus (HIV).&#xD;
&#xD;
          -  Serologic status reflecting active hepatitis B or C infection.&#xD;
&#xD;
          -  History of known hypersensitivity or anaphylactic reactions to study drugs or&#xD;
             excipients.&#xD;
&#xD;
          -  History of stroke or intracranial hemorrhage within 6 months before first dose of&#xD;
             study drug.&#xD;
&#xD;
          -  Known bleeding disorders.&#xD;
&#xD;
          -  Requires or receiving anticoagulation with warfarin or equivalent vitamin K&#xD;
             antagonists.&#xD;
&#xD;
          -  Female participants must not be breastfeeding or pregnant.&#xD;
&#xD;
          -  Concurrent participation in another therapeutic clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>AstraZeneca Clinical Study Information Center</last_name>
    <phone>1-877-240-9479</phone>
    <email>information.center@astrazeneca.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Redondo Beach</city>
        <state>California</state>
        <zip>90277</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <zip>93105</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40207</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70056</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fort Sam Houston</city>
        <state>Texas</state>
        <zip>78234</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99208</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1114</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1426ANZ</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Capital Federal</city>
        <zip>1118</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Córdoba</city>
        <zip>5000</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Adelaide</city>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Darlinghurst</city>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Heidelberg</city>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kogarah</city>
        <zip>2217</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Melbourne</city>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nedlands</city>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Waratah</city>
        <zip>2298</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Woolloongabba</city>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Krems</city>
        <zip>3500</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Vienna</city>
        <zip>1140</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Goiania</city>
        <zip>74605-020</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90020-090</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90035-003</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90110-270</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>20230-130</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>22793-080</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>01236-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>01509-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>05403-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>São Paulo</city>
        <zip>01308-050</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Plovdiv</city>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1606</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1606</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Vratsa</city>
        <zip>3000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4J 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Quebec</city>
        <zip>G1J 1Z4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beijing</city>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beijing</city>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beijing</city>
        <zip>100191</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Changchun</city>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Changsha</city>
        <zip>410008</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chengdu</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chongqing</city>
        <zip>400037</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fuzhou</city>
        <zip>350001</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Guangzhou</city>
        <zip>510100</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Guangzhou</city>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Haikou</city>
        <zip>570311</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hangzhou</city>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nanchang</city>
        <zip>330006</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nanjing</city>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shengyang</city>
        <zip>110004</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shenyang</city>
        <zip>110001</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shenzhen</city>
        <zip>518039</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tianjin</city>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Urumchi</city>
        <zip>830054</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wenzhou</city>
        <zip>325000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wuhan</city>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wuhan</city>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Xian</city>
        <zip>710061</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zhengzhou</city>
        <zip>450008</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zhengzhou</city>
        <zip>450052</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zhongshan</city>
        <zip>528403</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brno</city>
        <zip>625 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Olomouc</city>
        <zip>779 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ostrava</city>
        <zip>708 52</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Plzen</city>
        <zip>304 60</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Praha</city>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Odense C</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Roskilde</city>
        <zip>4000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Montpellier Cedex 5</city>
        <zip>34090</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Paris Cedex 10</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pessac</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pierre Benite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rennes Cedex 9</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rouen Cedex 1</city>
        <zip>76038</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toulouse Cedex 9</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hamburg</city>
        <zip>20099</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Köln</city>
        <zip>50924</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Paderborn</city>
        <zip>33098</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Potsdam</city>
        <zip>14467</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Würzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Budapest</city>
        <zip>1083</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Budapest</city>
        <zip>1125</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kaposvár</city>
        <zip>7400</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Haifa</city>
        <zip>31999</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Petah Tiqva</city>
        <zip>49100</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tel Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tel Hashomer</city>
        <zip>52620</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Meldola</city>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Milano</city>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ravenna</city>
        <zip>48121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Incheon</city>
        <zip>21565</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>D.F</city>
        <zip>14050</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Mexico</city>
        <zip>01710</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Monterrey</city>
        <zip>64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Monterrey</city>
        <zip>64570</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Morelia</city>
        <zip>58260</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Almere</city>
        <zip>1315 RA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Arnhem</city>
        <zip>6815 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Breda</city>
        <zip>4818 CK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Den Bosch</city>
        <zip>5223 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nieuwegein</city>
        <zip>3435 CM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brzozów</city>
        <zip>36-200</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-168</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gdynia</city>
        <zip>81-519</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Krakow</city>
        <zip>30-727</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lublin</city>
        <zip>20-081</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wrocław</city>
        <zip>50-367</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wrocław</city>
        <zip>50-556</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Łódź</city>
        <zip>93-510</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Moscow</city>
        <zip>125284</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197347</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Samara</city>
        <zip>443095</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sochi</city>
        <zip>354057</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>St Petersburg</city>
        <zip>197341</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tula</city>
        <zip>300053</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Volgograd</city>
        <zip>400138</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dammam</city>
        <zip>31444</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jeddah</city>
        <zip>21423</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Riyadh</city>
        <zip>12713</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Riyadh</city>
        <zip>14611</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bratislava</city>
        <zip>83310</zip>
        <country>Slovakia</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bloemfontein</city>
        <zip>9301</zip>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cape Town</city>
        <zip>7925</zip>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Johannesburg</city>
        <zip>2013</zip>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pretoria</city>
        <zip>0044</zip>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Randburg</city>
        <zip>2125</zip>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Badalona(Barcelona)</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28031</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Majadahonda</city>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santander</city>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Valencia</city>
        <zip>46009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Göteborg</city>
        <zip>41345</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Uppsala</city>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Örebro</city>
        <zip>70185</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kaohsiung</city>
        <zip>833</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taichung</city>
        <zip>404</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tainan City</city>
        <zip>70403</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taoyuan City</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Izmir</city>
        <zip>35340</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kurupelit</city>
        <zip>55139</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Talas</city>
        <zip>38280</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cherkasy</city>
        <zip>18009</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dnipro</city>
        <zip>49102</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ivano-Frankivsk</city>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kharkiv Region</city>
        <zip>61070</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Khmelnytskyi</city>
        <zip>29000</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kyiv</city>
        <zip>03022</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zhytomyr</city>
        <zip>10002</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Canterbury</city>
        <zip>CT1 3NG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wolverhampton</city>
        <zip>WV10 OQP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Brazil</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>China</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Saudi Arabia</country>
    <country>Slovakia</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Belgium</country>
    <country>Peru</country>
  </removed_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CLL</keyword>
  <keyword>Chronic Leukemia Lymphocytic</keyword>
  <keyword>Leukemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Venetoclax</mesh_term>
    <mesh_term>Obinutuzumab</mesh_term>
    <mesh_term>Acalabrutinib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03836261
org study id: ACE-CL-311
secondary id: D8221C00001
secondary id: 2018-002443-28
nct id: NCT03836261
nct alias: NCT05211856
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in
      combination with venetoclax and acalabrutinib in combination with venetoclax with and without
      obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL
This randomized, global, multicenter, open-label, Phase 3 study will evaluate the efficacy
      and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in subjects with previously
      untreated CLL without del(17p) or TP53. Subjects will be randomized in a 1:1:1 ratio into 3
      arms through a block stratified randomization procedure.

      The study includes screening (35 days), treatment (from randomization until study drug
      discontinuation) and follow-up phase.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS
time frame: 6 years
description: Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria
measure: To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS
time frame: 6 years
description: PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment
measure: To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared with FCR or BR (Arm C): PFS defined the same as above per investigator assessment.
time frame: 6 years
description: PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment
arm group label: Acalabrutinib, Venetoclax
arm group type: Experimental
description: Acalabrutinib in combination with Venetoclax
arm group label: Acalabrutinib, Venetoclax, Obinutuzumab
arm group type: Experimental
description: Acalabrutinib in combination with Venetoclax with or without Obinutuzumab
arm group label: Chemoimmunotherapy
arm group type: Active Comparator
description: Chemoimmunotherapy
FCR: Fludarabine, Cyclophosphamide and Rituximab
intervention type: Drug
intervention name: Acalabrutinib
description: Acalabrutinib,
arm group label: Acalabrutinib, Venetoclax
arm group label: Acalabrutinib, Venetoclax, Obinutuzumab
other name: Calquence (acalabrutinib)
intervention type: Drug
intervention name: Venetoclax
description: Venetoclax
arm group label: Acalabrutinib, Venetoclax
arm group label: Acalabrutinib, Venetoclax, Obinutuzumab
other name: Venclyxto, Venclexta
intervention type: Drug
intervention name: Chemoimmunotherapy
description: fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)
arm group label: Chemoimmunotherapy
intervention type: Drug
intervention name: Obinutuzumab
description: Obinutuzumab
arm group label: Acalabrutinib, Venetoclax, Obinutuzumab
other name: Gazyva, Gazyvaro
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
last name: AstraZeneca Clinical Study Information Center
phone: 1-877-240-9479
email: information.center@astrazeneca.com
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Completed
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Completed
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Not yet recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Completed
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
country: Argentina
country: Australia
country: Austria
country: Brazil
country: Bulgaria
country: Canada
country: China
country: Czechia
country: Denmark
country: France
country: Germany
country: Hungary
country: Israel
country: Italy
country: Korea, Republic of
country: Mexico
country: Netherlands
country: Poland
country: Russian Federation
country: Saudi Arabia
country: Slovakia
country: South Africa
country: Spain
country: Sweden
country: Taiwan
country: Turkey
country: Ukraine
country: United Kingdom
country: United States
country: Belgium
country: Peru
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Venetoclax
mesh term: Obinutuzumab
mesh term: Acalabrutinib