xml: <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/NCT06033820</url>
    </required_header>
    <id_info>
      <org_study_id>IIT-2022-0229</org_study_id>
      <nct_id>NCT06033820</nct_id>
    </id_info>
    <brief_title>Zanubrutinib+Lenalidomide+R-ICE in Relapsed/Refractory DLBCL</brief_title>
    <official_title>A Prospective, Single Arm, Open Label Study to Evaluate the Safety and Efficacy of Zanubrutinib, Lenalidomide With R-ICE Chemotherapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>RenJi Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>RenJi Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a prospective, single center, single arm, open label study of zanubrutinib,&#xD;
        lenalidomide in combination with Rituximab-ICE for treatment of relapsed/refractory diffuse&#xD;
        large B-cell lymphoma.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2025</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>Objective response rate (ORR)</measure>
      <time_frame>9 weeks</time_frame>
      <description>To evaluate the efficacy in terms of objective response rate including CR and PR rate after three cycles of ZR2-ICE</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Complete remission rate (CR)</measure>
      <time_frame>9 weeks</time_frame>
      <description>To evaluate the efficacy in terms of Complete Response Rate after three cycles of ZR2-ICE</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DOR</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Among participants who experience an objective response, DOR is defined as the date of their first objective response (which is subsequently confirmed) to disease progression</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Progression-free survival is defined as the time from enrolment to progression or death due to any cause. The distribution of PFS will be estimated using the method of Kaplan-Meier.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Overall survival is defined as the time from enrolment to death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Management Study</measure>
      <time_frame>Up to 100 days</time_frame>
      <description>Incidence and Severity of Toxicities</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Diffuse Large B Cell Lymphoma | Diffuse Large B-Cell Lymphoma Recurrent/Refractory</condition>
    <arm_group>
      <arm_group_label>Participant Group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>All patients will receive 3 cycles of ZR2-ICE immunochemotherapy every three weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ZR2-ICE</intervention_name>
      <description>Drug: zanubrutinib Oral Capsule&#xD;
  Drug: lenalidomide Oral Capsule&#xD;
  Drug: R-ICE chemotherapy</description>
      <arm_group_label>Participant Group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          1. Age between 18 years and 75 years 2. Histologically confirmed diagnosis of DLBCL, CD20&#xD;
          positive 3. Patients received at least one systemic regimens for the treatment of DLBCL,&#xD;
          and one therapy line must have included a CD20-targeted therapy.&#xD;
  &#xD;
          4. Relapsed or refractory disease 5. Eastern Cooperative Oncology Group (ECOG) performance&#xD;
          status of 0-2. 6. Measurable disease on cross section imaging by PET and/or CT that is at&#xD;
          least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions as&#xD;
          defined by IWG criteria.&#xD;
  &#xD;
          7. Patients must meet the following laboratory criteria at screening, including:&#xD;
  &#xD;
            1. Absolute neutrophil count (ANC) ≥1.5 x 109/L or ≥0.75 x 109/L if bone marrow&#xD;
               involvement&#xD;
  &#xD;
            2. Platelets ≥90 x 109/L or ≥50 x 109/L if bone marrow involvement&#xD;
  &#xD;
            3. Hemoglobin ≥75 g/dL or ≥50 g/dL if bone marrow involvement&#xD;
  &#xD;
            4. Total bilirubin ≤2.5 x upper limit of normal (ULN) unless bilirubin rise is due to&#xD;
               Gilbert's syndrome or of hepatic involvement.&#xD;
  &#xD;
            5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline&#xD;
               phosphatase (ALP) ≤3 x (ULN) or &lt; 5 x ULN if hepatic involvement.&#xD;
  &#xD;
            6. Creatinine Clearance Rate ≥60 mL/min.&#xD;
  &#xD;
            7. INR ≤1.5 x ULN and aPTT ≤1.5 x ULN 8. Women of childbearing potential must have a&#xD;
               negative serum (beta-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at&#xD;
               Screening. Women who are pregnant or breastfeeding are ineligible for this study.&#xD;
               Women of childbearing potential and men who are sexually active must be practicing a&#xD;
               highly effective method of birth control during and after the study consistent with&#xD;
               local regulations regarding the use of birth control methods for subjects&#xD;
               participating in clinical trials. For females, these restrictions apply for 3 month&#xD;
               after the last dose of study drug.&#xD;
  &#xD;
          9. Male subject agrees to use an acceptable method for contraception for the duration of&#xD;
          the study. Men must agree to not donate sperm during and after the study. For males, these&#xD;
          restrictions apply for 3 months after the last dose of study drug.&#xD;
  &#xD;
          10. Sign an informed consent document indicating that they understand the purpose of and&#xD;
          procedures required for the study, and are willing to participate in the study. Must be&#xD;
          able to adhere to study visit schedules and other protocol requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          1. Patients who have a history of &quot;double/triple hit&quot; genetics. 2. Patients who have,&#xD;
          within 14 days prior to Day 1 dosing:&#xD;
  &#xD;
            1. not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational&#xD;
               anticancer therapy or other lymphoma specific therapy.&#xD;
  &#xD;
            2. undergone major surgery or suffered from significant traumatic injury.&#xD;
  &#xD;
            3. received live vaccines.&#xD;
  &#xD;
            4. required parenteral antimicrobial therapy for active, intercurrent infections. 3.&#xD;
               Patients who have use investigational agents within the period ≤ 3 months prior to Day&#xD;
               1 dosing.&#xD;
  &#xD;
          4. Patients who have,&#xD;
  &#xD;
            1. Adverse events (AEs) due to previous anti-tumor therapy have not recovered&#xD;
  &#xD;
            2. Known allergy or sensitivity to any drug contained in the regimen&#xD;
  &#xD;
            3. have undergone ASCT within the period ≤3 months prior to signing the informed consent&#xD;
               form.&#xD;
  &#xD;
            4. have undergone previous allogenic stem cell transplantation.&#xD;
  &#xD;
            5. have a history of deep venous thrombosis/embolism and who are not willing/able to take&#xD;
               venous thromboembolic event prophylaxis during the entire treatment period.&#xD;
  &#xD;
            6. concurrently use other anticancer or experimental treatments. 5. Coexistent second&#xD;
               malignancy or history of prior malignancy within previous 5 years.&#xD;
  &#xD;
          6. Patients who have,&#xD;
  &#xD;
            1. Known history of active Hepatitis C Virus or active Hepatitis B Virus infection or any&#xD;
               uncontrolled active systemic infection requiring intravenous (IV) antibiotics.&#xD;
  &#xD;
            2. Known history of human immunodeficiency virus (HIV) infection.&#xD;
  &#xD;
            3. Any significant medical or psychiatric condition that might prevent the patient from&#xD;
               complying with all study procedures.&#xD;
  &#xD;
            4. History of gastrointestinal disorder or defect that would interfere with the&#xD;
               absorption of the study drug.&#xD;
  &#xD;
            5. Patients with history of severe hemorrhagic disorders.&#xD;
  &#xD;
            6. History of stroke or intracranial hemorrhage within 6 months prior to registration&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Hong-Hui Huang, Professor</last_name>
      <phone>008613661793444</phone>
      <email>huanghonghui@renji.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 5, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 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>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06033820
  org study id: IIT-2022-0229
  nct id: NCT06033820
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This is a prospective, single center, single arm, open label study of zanubrutinib,
        lenalidomide in combination with Rituximab-ICE for treatment of relapsed/refractory diffuse
        large B-cell lymphoma.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective response rate (ORR)
  time frame: 9 weeks
  description: To evaluate the efficacy in terms of objective response rate including CR and PR rate after three cycles of ZR2-ICE
  measure: Complete remission rate (CR)
  time frame: 9 weeks
  description: To evaluate the efficacy in terms of Complete Response Rate after three cycles of ZR2-ICE
  measure: DOR
  time frame: Up to 2 years
  description: Among participants who experience an objective response, DOR is defined as the date of their first objective response (which is subsequently confirmed) to disease progression
  measure: Progression-free survival
  time frame: Up to 2 years
  description: Progression-free survival is defined as the time from enrolment to progression or death due to any cause. The distribution of PFS will be estimated using the method of Kaplan-Meier.
  measure: Overall survival
  time frame: Up to 2 years
  description: Overall survival is defined as the time from enrolment to death due to any cause.
  measure: Safety Management Study
  time frame: Up to 100 days
  description: Incidence and Severity of Toxicities
  arm group label: Participant Group
  arm group type: Experimental
  description: All patients will receive 3 cycles of ZR2-ICE immunochemotherapy every three weeks.
  intervention type: Drug
  intervention name: ZR2-ICE
  description: Drug: zanubrutinib Oral Capsule
  Drug: lenalidomide Oral Capsule
  Drug: R-ICE chemotherapy
  arm group label: Participant Group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Hong-Hui Huang, Professor
  phone: 008613661793444
  email: huanghonghui@renji.com
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Lymphoma, B-Cell
  mesh term: Lymphoma, Large B-Cell, Diffuse
  sharing ipd: No