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/NCT06005870</url>
    </required_header>
    <id_info>
      <org_study_id>UHCT22242</org_study_id>
      <nct_id>NCT06005870</nct_id>
    </id_info>
    <brief_title>Zanubrutinib Combined With R-CHOP in the Treatment of Newly Diagnosed DLBCL With p53 Protein Expression</brief_title>
    <official_title>Zanubrutinib Combined With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma With p53 Protein Expression</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Huazhong University of Science and Technology</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Huazhong University of Science and Technology</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 study aim to evaluate the efficacy and safety of zanubrutinib combined with R-CHOP in&#xD;
        the treatment of DLBCL patients with p53 protein expression.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a prospective, single arm, single center study,it plans to recruit 41 newly diagnosed&#xD;
        DLBCL patients with p53 protein expression(≥50%).According to Simon's two-stage optimal&#xD;
        design criteria, 19 eligible patients were recruited in the first phase, and at least 12&#xD;
        patients were required to achieve complete response to enter the second phase. In phase 2,&#xD;
        additional 22 patients were recruited. These patients will receive zanubrutinib plus RCHOP&#xD;
        for 6 cycles. After 4 treatment cycles, an interim response assessment will be performed to&#xD;
        evaluate disease progression for each participant. Participants with progressive or stable&#xD;
        disease will be discontinued from treatment，Participants with complete/partial response will&#xD;
        continue ZRCHOP until 6 cycles are completed.After completion of study drug, participants&#xD;
        will undergo assessment of tumor response based on the Revised Response Criteria for&#xD;
        Malignant Lymphoma.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">November 26, 2022</start_date>
    <completion_date type="Anticipated">December 2026</completion_date>
    <primary_completion_date type="Anticipated">December 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>Complete response rate (CRR)</measure>
      <time_frame>At the end of cycle 6 (each cycle is 21 days )</time_frame>
      <description>To evaluate the efficacy of anti-lymphoma</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall response rate (ORR)</measure>
      <time_frame>At the end of cycle 6 (each cycle is 21 days )</time_frame>
      <description>To evaluate the efficacy of anti-lymphoma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>From date of initiation therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months</time_frame>
      <description>To evaluate the efficacy of anti-lymphoma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>From date of initiation therapy until the date of death from any cause, assessed up to 60 months</time_frame>
      <description>To evaluate the efficacy of anti-lymphoma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of AE and SAE</measure>
      <time_frame>from the initiation of the first dose to 28 days after the last dose</time_frame>
      <description>To identify the incidence of AE and SAE in clinical trial</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">41</enrollment>
    <condition>Diffuse Large B Cell Lymphoma</condition>
    <arm_group>
      <arm_group_label>Z-RCHOP</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with newly diagnosed DLBCL with p53 expression were treated with a combination of Zanubrutinib and RCHOP.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Zanubrutinib plus RCHOP</intervention_name>
      <description>Rituximab 375mg/m2 D1; cyclophosphamide 750mg/m2 D2; adriamycin 50 mg/m2 D2 vincristine 1.4mg/m(Max 2mg) D2; prednisone 100mg/d D2-6; Zanubrutinib 160 mg, the bid D1-21</description>
      <arm_group_label>Z-RCHOP</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years, ≤ 75 years, both sexes;&#xD;
  &#xD;
            2. Diff use large B-cell lymphoma diagnosed by histopathology without previous systemic&#xD;
               DLBCL treatment;&#xD;
  &#xD;
            3. ECOG score: 0-2;&#xD;
  &#xD;
            4. Predicted survival ≥3 months;&#xD;
  &#xD;
            5. Patients with positive p53 expression detected by immunohistochemistry (≥50% );&#xD;
  &#xD;
            6. The patients had certain conditions of organ function reserve, and the laboratory&#xD;
               tests within 1 week before enrollment met the following conditions:&#xD;
  &#xD;
          Blood routine: neutrophil count (NEUT) ≥1.5×10^9/L, platelet count (PLT)&#xD;
  &#xD;
          ≥75×10^9/L, hemoglobin (HGB) ≥80 g/L; G-CSF was not used in the past 7 days (the&#xD;
          researchers judged that the lymphoma-induced cytopenia could be included).&#xD;
  &#xD;
          Liver function: Total bilirubin (TBIL) ≤1.5× upper limit of the normal range (ULN); Alanine&#xD;
          aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; If liver metastases&#xD;
          were present, TBIL≤3×ULN, ALT and AST≤5×ULN; Renal function: serum creatinine (Cr) ≤2.0×ULN&#xD;
          or creatinine clearance (CCr) ≥60ml/min;&#xD;
  &#xD;
          Cardiac function: LVEF≥50%, ECG did not indicate any acute myocardial infarction,&#xD;
          arrhythmia, or atrioventricular conduction block above grade I;&#xD;
  &#xD;
          Thyroid function: thyroid stimulating hormone (TSH) was within the normal range. If TSH is&#xD;
          abnormal, free triiodothyronine (FT3) and free thyroxine (FT4) should be within the normal&#xD;
          range or abnormal without clinical significance.&#xD;
  &#xD;
            1. According to the Lugano2014 assessment criteria, patients must have measurable&#xD;
               lesions, defined as the longest diameter of at least one nodule &gt; 1.5cm, or the&#xD;
               longest diameter of at least one nodule &gt; 1cm, and at least two vertical diameters&#xD;
               that can be accurately measured.&#xD;
  &#xD;
            2. Patients volunteered to participate in the trial, understood the study procedure, and&#xD;
               were able to sign in-person informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with definite lymphoma central nervous system (CNS) infiltration, including&#xD;
               brain parenchyma, meningeal invasion, or spinal cord compression;&#xD;
  &#xD;
            2. severe or uncontrolled infection;&#xD;
  &#xD;
            3. with active autoimmune disease;&#xD;
  &#xD;
            4. Other serious medical conditions, such as uncontrolled diabetes, gastric ulcers, other&#xD;
               serious cardiopulmonary diseases, etc. (the decision was left to the investigator);&#xD;
  &#xD;
            5. patients who received the live attenuated vaccine within 4 weeks before the first dose&#xD;
               or planned to receive the live attenuated vaccine during the study;&#xD;
  &#xD;
            6. The subject has previous or co -e xis ting other malignant tumors; Patients with basal&#xD;
               cell carcinoma of the skin and uterine and neck carcinoma in situ who had been cured&#xD;
               for more than 3 years, and patients with other malignant tumors who had been cured for&#xD;
               more than 5 years were considered for inclusion.&#xD;
  &#xD;
            7. HIV-positive patients with active hepatitis B ( HBV-DNA &gt; 100 copies/m L), positive&#xD;
               HCV antibody, or abnormal HCV-RNA&#xD;
  &#xD;
            8. Women who were pregnant or lactating, women who planned to become pregnant between the&#xD;
               study period and 6 months after the last dose, or men whose partners planned to become&#xD;
               pregnant, who were unwilling to use a medically approve defective contraceptive method&#xD;
               (e.g., intrauterine device or condom ) during the trial;&#xD;
  &#xD;
            9. were allergic to any of the drugs in the study protocol;&#xD;
  &#xD;
           10. ineligible for inclusion as judged by the investigator ;&#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_official>
      <last_name>Liling Zhang, M.D</last_name>
      <role>Study Chair</role>
      <affiliation>Wuhan Union Hospital, China</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Liling Zhang, M.D</last_name>
      <phone>15871725926</phone>
      <email>15871725926lily1228@sina.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Union Hospital, Tongji Medical College, Huazhong University of Science and Technology</name>
        <address>
          <city>Wuhan</city>
          <state>Hubei</state>
          <zip>430022</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Liling Zhang, M.D</last_name>
        <phone>15871725926</phone>
        <email>15871725926lily1228@sina.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Huazhong University of Science and Technology</investigator_affiliation>
      <investigator_full_name>Liling Zhang</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>DLBCL</keyword>
    <keyword>Diffuse Large b-cell lymphoma</keyword>
    <keyword>p53</keyword>
    <keyword>zanubrutinib</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphoma</mesh_term>
      <mesh_term>Lymphoma, B-Cell</mesh_term>
      <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Zanubrutinib</mesh_term>
    </intervention_browse>
    <!-- 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/NCT06005870
  org study id: UHCT22242
  nct id: NCT06005870
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This study aim to evaluate the efficacy and safety of zanubrutinib combined with R-CHOP in
        the treatment of DLBCL patients with p53 protein expression.
  This is a prospective, single arm, single center study,it plans to recruit 41 newly diagnosed
        DLBCL patients with p53 protein expression(≥50%).According to Simon's two-stage optimal
        design criteria, 19 eligible patients were recruited in the first phase, and at least 12
        patients were required to achieve complete response to enter the second phase. In phase 2,
        additional 22 patients were recruited. These patients will receive zanubrutinib plus RCHOP
        for 6 cycles. After 4 treatment cycles, an interim response assessment will be performed to
        evaluate disease progression for each participant. Participants with progressive or stable
        disease will be discontinued from treatment，Participants with complete/partial response will
        continue ZRCHOP until 6 cycles are completed.After completion of study drug, participants
        will undergo assessment of tumor response based on the Revised Response Criteria for
        Malignant Lymphoma.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Complete response rate (CRR)
  time frame: At the end of cycle 6 (each cycle is 21 days )
  description: To evaluate the efficacy of anti-lymphoma
  measure: Overall response rate (ORR)
  time frame: At the end of cycle 6 (each cycle is 21 days )
  description: To evaluate the efficacy of anti-lymphoma
  measure: Progression-free survival (PFS)
  time frame: From date of initiation therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
  description: To evaluate the efficacy of anti-lymphoma
  measure: Overall survival (OS)
  time frame: From date of initiation therapy until the date of death from any cause, assessed up to 60 months
  description: To evaluate the efficacy of anti-lymphoma
  measure: Rate of AE and SAE
  time frame: from the initiation of the first dose to 28 days after the last dose
  description: To identify the incidence of AE and SAE in clinical trial
  arm group label: Z-RCHOP
  arm group type: Experimental
  description: Patients with newly diagnosed DLBCL with p53 expression were treated with a combination of Zanubrutinib and RCHOP.
  intervention type: Drug
  intervention name: Zanubrutinib plus RCHOP
  description: Rituximab 375mg/m2 D1; cyclophosphamide 750mg/m2 D2; adriamycin 50 mg/m2 D2 vincristine 1.4mg/m(Max 2mg) D2; prednisone 100mg/d D2-6; Zanubrutinib 160 mg, the bid D1-21
  arm group label: Z-RCHOP
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Liling Zhang, M.D
  role: Study Chair
  affiliation: Wuhan Union Hospital, China
  last name: Liling Zhang, M.D
  phone: 15871725926
  email: 15871725926lily1228@sina.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Huazhong University of Science and Technology
  investigator full name: Liling Zhang
  investigator title: Professor
  mesh term: Lymphoma
  mesh term: Lymphoma, B-Cell
  mesh term: Lymphoma, Large B-Cell, Diffuse
  mesh term: Zanubrutinib