<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/NCT04460248</url>
  </required_header>
  <id_info>
    <org_study_id>ZR2</org_study_id>
    <nct_id>NCT04460248</nct_id>
  </id_info>
  <brief_title>Zanubrutinib, Lenalidomide and Rituximab (ZR2) in Elderly Treatment-naive Patients With Diffuse Large B-cell Lymphoma (DLBCL)</brief_title>
  <official_title>The Efficacy and Safety of Zanubrutinib, Lenalidomide and Rituximab (ZR2) Regimen in Elderly Treatment-naive Patients With Diffuse Large B-cell Lymphoma (DLBCL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ruijin Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is a prospective, single-center, open-label, single-arm clinical study designed to&#xD;
      evaluate the efficacy and safety of the Zanubrutinib, Lenalidomide and Rituximab (ZR2)&#xD;
      regimen in elderly treatment-naive patient with diffuse large B-cell lymphomas.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 22, 2020</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Actual">February 16, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete response rate</measure>
    <time_frame>At the end of Cycle 6 (each cycle is 21 days)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>2-year progression-free survival</measure>
    <time_frame>2 years after enrollment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2-year overall survival</measure>
    <time_frame>2 years after enrollment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of adverse events</measure>
    <time_frame>From enrollment to study completion, a maximum of 3 years.</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Single-cell ribonucleic acid (scRNA) sequencing</measure>
    <time_frame>From enrollment to study completion, a maximum of 3 years.</time_frame>
    <description>scRNA sequencing in tumor tissue</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Zanubrutinib, Lenalidomide and Rituximab (ZR2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zanubrutinib, Lenalidomide and Rituximab (ZR2)</intervention_name>
    <description>Induction therapy:&#xD;
The ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles.&#xD;
Dosage:&#xD;
Zanubrutinib, 160 mg bid, po, day 1-21;&#xD;
Lenalidomide, 25 mg qd, po, day 2-11;&#xD;
Rituximab, 375 mg/m2, ivgtt, day 1.&#xD;
Maintenance therapy:&#xD;
Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days, for a maximum of 2 years.</description>
    <arm_group_label>Zanubrutinib, Lenalidomide and Rituximab (ZR2)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Treatment-naive pathologically confirmed patients with diffuse large B-cell lymphoma&#xD;
             (DLBCL)&#xD;
&#xD;
          -  Reluctant to undergo systemic chemotherapy or not suitable for chemotherapy defined as&#xD;
             ECOG&gt;2, ADL&lt;100 or CCI&gt;1&#xD;
&#xD;
          -  Radiography detects measurable lesions defined as at least 1 clearly defined&#xD;
             lesion/nodule with both long and short diameters longer than or equal to 1.5cm&#xD;
&#xD;
          -  Life expectancy of at least 3 months determined by researchers&#xD;
&#xD;
          -  The patient or his or her legal representative must provide written informed consent&#xD;
             prior to any special examination or procedure for the research&#xD;
&#xD;
          -  Research drugs have not been used before&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The patient has received systemic or local anti-lymphoma treatment, including&#xD;
             chemotherapy, within three weeks before enrollment&#xD;
&#xD;
          -  The patient has complications of uncontrolled cardiovascular diseases, blood clotting&#xD;
             disorders, connective tissue diseases, serious infectious diseases and other diseases&#xD;
&#xD;
          -  Laboratory measures meet the following criteria at screening (unless caused by&#xD;
             lymphoma):&#xD;
&#xD;
               1. Neutrophils&lt;1.5 x 10^9/L&#xD;
&#xD;
               2. Platelets&lt;80 x 10^9/L&#xD;
&#xD;
               3. ALT or AST is 2 times higher than the normal upper limit, AKP and bilirubin are&#xD;
                  1.5 times higher than normal upper limit&#xD;
&#xD;
               4. Creatinine is 1.5 times higher than the normal upper limit&#xD;
&#xD;
          -  Other concurrent and uncontrolled medical conditions that the researchers believe that&#xD;
             they will affect the patient's participation in the study, including patients with&#xD;
             psychosis or other known or suspected patients who cannot fully comply with the&#xD;
             research protocol&#xD;
&#xD;
          -  HIV-infected patients&#xD;
&#xD;
          -  Patients with HbsAg positive are required to have negative HBV DNA before entering the&#xD;
             group. In addition, if the patient is HBsAg negative but HBcAb positive (regardless of&#xD;
             HBsAb status), HBV DNA test is also required, and if the result is positive,&#xD;
             anti-viral treatment is also required, and negative HBV DNA is required before&#xD;
             entering the group&#xD;
&#xD;
          -  Other medical conditions determined by the researchers that may affect the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>75 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shanghai Ruijin Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>April 19, 2022</last_update_submitted>
  <last_update_submitted_qc>April 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ruijin Hospital</investigator_affiliation>
    <investigator_full_name>Zhao Weili</investigator_full_name>
    <investigator_title>First Deputy Director of Shanghai Institute of Hematology</investigator_title>
  </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>Rituximab</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Zanubrutinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04460248
org study id: ZR2
nct id: NCT04460248
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective, single-center, open-label, single-arm clinical study designed to
      evaluate the efficacy and safety of the Zanubrutinib, Lenalidomide and Rituximab (ZR2)
      regimen in elderly treatment-naive patient with diffuse large B-cell lymphomas.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete response rate
time frame: At the end of Cycle 6 (each cycle is 21 days)
measure: 2-year progression-free survival
time frame: 2 years after enrollment
measure: 2-year overall survival
time frame: 2 years after enrollment
measure: Incidence rate of adverse events
time frame: From enrollment to study completion, a maximum of 3 years.
measure: Single-cell ribonucleic acid (scRNA) sequencing
time frame: From enrollment to study completion, a maximum of 3 years.
description: scRNA sequencing in tumor tissue
arm group label: Zanubrutinib, Lenalidomide and Rituximab (ZR2)
arm group type: Experimental
intervention type: Drug
intervention name: Zanubrutinib, Lenalidomide and Rituximab (ZR2)
description: Induction therapy:
The ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles.
Dosage:
Zanubrutinib, 160 mg bid, po, day 1-21;
Lenalidomide, 25 mg qd, po, day 2-11;
Rituximab, 375 mg/m2, ivgtt, day 1.
Maintenance therapy:
Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days, for a maximum of 2 years.
arm group label: Zanubrutinib, Lenalidomide and Rituximab (ZR2)
criteria: 
gender: All
minimum age: 75 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Ruijin Hospital
investigator full name: Zhao Weili
investigator title: First Deputy Director of Shanghai Institute of Hematology
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Rituximab
mesh term: Lenalidomide
mesh term: Zanubrutinib
sharing ipd: No