<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/NCT04436107</url>
  </required_header>
  <id_info>
    <org_study_id>BGB-3111-110</org_study_id>
    <nct_id>NCT04436107</nct_id>
  </id_info>
  <brief_title>Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma</brief_title>
  <official_title>A Phase 1, Open Label, Multiple Dose, Dose Escalation and Expansion Study of Bruton Tyrosine Kinase (BTK) Inhibitor, Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BeiGene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BeiGene</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine the maximum tolerated doses (MTD) and the&#xD;
      recommended Phase 2 dose (RP2D), and safety and tolerability of zanubrutinib in combination&#xD;
      with lenalidomide in participants with R/R DLBCL by dose escalating lenalidomide&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 11, 2020</start_date>
  <completion_date type="Anticipated">January 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Number of Participants Experiencing Adverse Events (AEs)</measure>
    <time_frame>Up to 48 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Number of Participants Experiencing Severe Adverse Events (SAEs)</measure>
    <time_frame>Up to 48 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Overall Response Rate (ORR)</measure>
    <time_frame>Up to 48 months</time_frame>
    <description>The proportion of participants who achieve either a partial response (PR) or complete response (CR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1: Overall Response Rate (ORR)</measure>
    <time_frame>Up to 48 months</time_frame>
    <description>The proportion of participants who achieve either a partial response (PR) or complete response (CR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve from Zero to Last Measurable Concentration (AUC0-t)</measure>
    <time_frame>Cycle 1 Day 1 (C1D1) and C1D21 up to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration (Cmax)</measure>
    <time_frame>C1D1 and C1D21 up to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum plasma concentration (Tmax)</measure>
    <time_frame>C1D1 and C1D21 up to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/F)</measure>
    <time_frame>C1D1 and C1D21 up to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Receptor Occupancy (Ro)</measure>
    <time_frame>C1D1 and C1D21 up to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Response Rate (CRR)</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR)</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">67</enrollment>
  <condition>Relapsed/Refractory Diffuse Large B-Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Part 1 : Zanubrutinib + Lenalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Zanubrutinib for up to 48 months&#xD;
Lenalidomide on Days 1 - 21 of each 28-Day cycle for up to 48 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 : Zanubrutinib+Lenalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Zanubrutinib for up to 48 months&#xD;
Lenalidomide at the RP2D dose determined from Part 1 administered on Days 1 - 21 of each 28-Day cycle for up to 48 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zanubrutinib</intervention_name>
    <description>160 mg administered orally twice daily (BID)</description>
    <arm_group_label>Part 1 : Zanubrutinib + Lenalidomide</arm_group_label>
    <arm_group_label>Part 2 : Zanubrutinib+Lenalidomide</arm_group_label>
    <other_name>BGB-3111</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Administered as specified in the treatment arm</description>
    <arm_group_label>Part 1 : Zanubrutinib + Lenalidomide</arm_group_label>
    <arm_group_label>Part 2 : Zanubrutinib+Lenalidomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed DLBCL, all participants must provide sufficient archival or&#xD;
             fresh tumor tissue samples for evaluation by immunohistochemistry (IHC) and Gene&#xD;
             Expression Profiling (GEP).&#xD;
&#xD;
          2. Relapsed or refractory disease, defined as either: 1) progression of disease after&#xD;
             having achieved disease remission (complete response [CR] or partial response [PR]) ,&#xD;
             or 2) stable disease (SD), or progressive disease (PD) at completion of the treatment&#xD;
             regimen preceding entry to the study.&#xD;
&#xD;
          3. Participants who have not received high dose therapy/stem cell transplantation&#xD;
             (HDT/SCT) must be ineligible for HDT/SCT.&#xD;
&#xD;
          4. Measurable disease as defined by at least 1 lymph node &gt;1.5 cm in longest diameter, or&#xD;
             at least 1 extra-nodal lesion &gt;1.0 cm in longest diameter, and measurable in 2&#xD;
             perpendicular dimensions.&#xD;
&#xD;
          5. Received an appropriate first-line therapy for DLBCL,defined as an anti CD20 antibody&#xD;
             and an appropriate anthracycline-based combination therapy for at least 2 cycles,&#xD;
             unless the patient is intolerant or had disease progression before Cycle 2..&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Current or history of central nervous system (CNS) lymphoma.&#xD;
&#xD;
          2. Histologically transformed lymphoma.&#xD;
&#xD;
          3. History of allogeneic stem-cell transplantation.&#xD;
&#xD;
          4. Prior exposure to a BTK inhibitor.&#xD;
&#xD;
          5. Prior exposure to lenalidomide or thalidomide.&#xD;
&#xD;
        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hui Yao, MD</last_name>
    <role>Study Director</role>
    <affiliation>BeiGene</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>BeiGene</last_name>
    <phone>1-877-828-5568</phone>
    <email>clinicaltrials@beigene.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Friendship Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Henan Cancer Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450008</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Union Hospital of Tongji Medical College, Huazhong University of Science and Technology</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Jilin Cancer Hospital</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>West China Hospital · Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Zhejiang Cancer Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Shanghai East Hospital</name>
      <address>
        <city>Shanghai</city>
        <zip>200120</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Tianjin Medical University Cancer Institute and Hospital</name>
      <address>
        <city>Tianjin</city>
        <zip>300060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>May 22, 2023</last_update_submitted>
  <last_update_submitted_qc>May 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, 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>Lenalidomide</mesh_term>
    <mesh_term>Zanubrutinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04436107
org study id: BGB-3111-110
nct id: NCT04436107
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to determine the maximum tolerated doses (MTD) and the
      recommended Phase 2 dose (RP2D), and safety and tolerability of zanubrutinib in combination
      with lenalidomide in participants with R/R DLBCL by dose escalating lenalidomide
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part 1: Number of Participants Experiencing Adverse Events (AEs)
time frame: Up to 48 months
measure: Part 1: Number of Participants Experiencing Severe Adverse Events (SAEs)
time frame: Up to 48 months
measure: Part 2: Overall Response Rate (ORR)
time frame: Up to 48 months
description: The proportion of participants who achieve either a partial response (PR) or complete response (CR)
measure: Part 1: Overall Response Rate (ORR)
time frame: Up to 48 months
description: The proportion of participants who achieve either a partial response (PR) or complete response (CR)
measure: Area Under the Curve from Zero to Last Measurable Concentration (AUC0-t)
time frame: Cycle 1 Day 1 (C1D1) and C1D21 up to 8 hours post-dose
measure: Maximum Concentration (Cmax)
time frame: C1D1 and C1D21 up to 8 hours post-dose
measure: Time to reach maximum plasma concentration (Tmax)
time frame: C1D1 and C1D21 up to 8 hours post-dose
measure: Apparent Clearance (CL/F)
time frame: C1D1 and C1D21 up to 8 hours post-dose
measure: Receptor Occupancy (Ro)
time frame: C1D1 and C1D21 up to 8 hours post-dose
measure: Complete Response Rate (CRR)
time frame: Up to 48 months
measure: Time to Response (TTR)
time frame: Up to 48 months
measure: Progression-Free Survival (PFS)
time frame: Up to 48 months
measure: Duration of Response (DOR)
time frame: Up to 48 months
arm group label: Part 1 : Zanubrutinib + Lenalidomide
arm group type: Experimental
description: Zanubrutinib for up to 48 months
Lenalidomide on Days 1 - 21 of each 28-Day cycle for up to 48 months
arm group label: Part 2 : Zanubrutinib+Lenalidomide
arm group type: Experimental
description: Zanubrutinib for up to 48 months
Lenalidomide at the RP2D dose determined from Part 1 administered on Days 1 - 21 of each 28-Day cycle for up to 48 months
intervention type: Drug
intervention name: Zanubrutinib
description: 160 mg administered orally twice daily (BID)
arm group label: Part 1 : Zanubrutinib + Lenalidomide
arm group label: Part 2 : Zanubrutinib+Lenalidomide
other name: BGB-3111
intervention type: Drug
intervention name: Lenalidomide
description: Administered as specified in the treatment arm
arm group label: Part 1 : Zanubrutinib + Lenalidomide
arm group label: Part 2 : Zanubrutinib+Lenalidomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hui Yao, MD
role: Study Director
affiliation: BeiGene
last name: BeiGene
phone: 1-877-828-5568
email: clinicaltrials@beigene.com
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
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Lenalidomide
mesh term: Zanubrutinib
sharing ipd: Yes