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/NCT05979948</url>
    </required_header>
    <id_info>
      <org_study_id>CZ-WM01</org_study_id>
      <nct_id>NCT05979948</nct_id>
    </id_info>
    <brief_title>A Phase 2 Clinical Trial to Evaluate Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia</brief_title>
    <acronym>CZ-WM01</acronym>
    <official_title>A Prospective, Open-label, Multicenter Study of Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai Changzheng Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>RenJi Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Huashan Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Shanghai 6th People's Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Huadong Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Shanghai Changzheng Hospital</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>
        This was a single-arm, multicenter, Phase 2 study to evaluate the efficacy of zanubrutinib&#xD;
        combined with BR (Bendamustine/Rituximab) regimen in Chinese participants with&#xD;
        newly-diagnosed Waldenström's macroglobulinemia who exhibited one or more of the criteria for&#xD;
        requiring treatment based on consensus guidelines from the 11th International Workshop on&#xD;
        Waldenström's Macroglobulinemia (IWWM). The investigators propose this combination will&#xD;
        improve the deep remission compared to single Zanubrutinib or BR regimen and can be a&#xD;
        time-limited regimen which will reduce the life-time therapy and benefit the patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study comprised an initial screening phase (up to 7 days), a single-arm treatment phase,&#xD;
        and a follow-up phase. Subjects with newly-diagnosed Waldenström's macroglobulinemia can&#xD;
        participate if all eligibility criteria are met. The participants will receive bendamustine&#xD;
        and rituximab for 6 28-day cycles. Bendamustine will be given intravenously at 70-90 mg/m2 on&#xD;
        days 1 and 2 of each cycle. Rituximab will be given on day 1 of each cycle (375 mg/m2&#xD;
        intravenously), Zanubrutinib will be given orally 160mg Bid per day, up to 12 months. The&#xD;
        participants with WM will also have disease assessment with Lymph node ultrasound and&#xD;
        abdominal ultrasound each cource, serum IgM, serum protein electrophoresis (SPE),&#xD;
        immunofixation (IFA), and viscosity assessments will be measured serially. A bone marrow&#xD;
        aspiration and biopsy flow cytometry examination will be done before treatment and at&#xD;
        response assessment at cycle 6 and 12. Durability of response will also be assessed every 3&#xD;
        months after treatment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">December 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">April 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>Overall Response Rate (ORR)</measure>
      <time_frame>up to the end of 12 cycles of treatment(each cycle is 28 days)</time_frame>
      <description>ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response</description>
    </primary_outcome>
    <primary_outcome>
      <measure>The best deep response rate</measure>
      <time_frame>Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)</time_frame>
      <description>defined as complete response (CR) and very good partial response (VGPR)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Progression-free Survival (PFS)</measure>
      <time_frame>Up to 6 years post first dose</time_frame>
      <description>PFS was defined as from the initiation of treatmentuntil to first documentation of progression or death, whichever comes first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Up to 6 years post first dose</time_frame>
      <description>OS is measured from the date of the initial of treatment to the date of the subject's death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>minimal residual disease (MRD) rate</measure>
      <time_frame>Up to 6 years post first dose</time_frame>
      <description>MRD will be assessed at two on treatment timepoints (before start of cycles 7, 12) and every 6 months thereafter. MRD will be measured through bone marrow samples using flow cytometrey.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Waldenström's Macroglobulinemia</condition>
    <arm_group>
      <arm_group_label>zanubrutinib combined with BR regimen</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: zanubrutinib,160 mg oral capsules twice daily for 12 months Drug: Bendamustine,70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles. Drug: Rituximab,375 mg/m2 intravenously on day 0 of each cycle for 6 cycles.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Zanubrutinib</intervention_name>
      <description>Zanubrutinib, 160 mg oral capsules twice daily for 12 months</description>
      <arm_group_label>zanubrutinib combined with BR regimen</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Bendamustine</intervention_name>
      <description>Bendamustine, 70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles.</description>
      <arm_group_label>zanubrutinib combined with BR regimen</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Rituximab</intervention_name>
      <description>Rituximab, 375 mg/m2 intravenously on day 0 of each cycle for 6 cycles</description>
      <arm_group_label>zanubrutinib combined with BR regimen</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Subjects must meet all of the following criteria to be enrolled:&#xD;
  &#xD;
            1. Newly diagnosed patients with waldenström's macroglobulinemia meeting at least one&#xD;
               criterion for treatment according to consensus panel criteria from the eleventh IWWM.&#xD;
  &#xD;
            2. ECOG score: 0-3 points, estimated survival time exceeding 3 months.&#xD;
  &#xD;
            3. Did not receive any treatment for Waldenström's macroglobulinemia before screening,&#xD;
               except for glucocorticoid therapy for autoimmune hemolysis.&#xD;
  &#xD;
            4. No serious damage to main organs, and meet the following laboratory examination&#xD;
               indicators: creatinine clearance rate≥40ml/min, total bilirubin≤1.5 times of the upper&#xD;
               limit of normal range; AST and ALT≤2.5 times of the upper limit of normal range;&#xD;
               Myocardial enzyme≤2 times of the upper limit of normal range; ECHO must demonstrate&#xD;
               left ventricular ejection fraction (LVEF) within the normal range, and no ECG&#xD;
               abnormality with clinical significance.&#xD;
  &#xD;
            5. Neutrophil count≥1.5×10^9/L without growth factor therapy within 7 days before&#xD;
               screening; Platelet count≥50×10^9/L without growth factor support or transfusion&#xD;
               within 7 days before screening; Hemoglobin≥60 g/L without erythropoietin (EPO) support&#xD;
               or transfusion within within 7 days before screening.&#xD;
  &#xD;
            6. No history of paroxysmal atrial fibrillation or chronic persistent atrial&#xD;
               fibrillation.&#xD;
  &#xD;
            7. Able to swallow and Oral administration.&#xD;
  &#xD;
            8. The subjects complete all screening and evaluations listed in all trial protocols.&#xD;
  &#xD;
            9. The subjects who signed the informed consent form for chemotherapy.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Waldenström's macroglobulinemia with amyloidosis or POEM syndrome&#xD;
  &#xD;
            2. HIV positive, or patients with active hepatitis A, hepatitis B, and hepatitis C&#xD;
               infection; Or the number of copies of hepatitis B virus&gt;10^2.&#xD;
  &#xD;
            3. Accompanied by other serious unstable diseases, including heart failure, renal&#xD;
               failure, liver failure, hemorrhagic diseases, uncontrollable diabetes, etc.&#xD;
  &#xD;
            4. In the past two years, the terminal organ was damaged due to autoimmune diseases (such&#xD;
               as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the&#xD;
               systemic use of immunosuppressive or other systemic disease control drugs was&#xD;
               required.&#xD;
  &#xD;
            5. Serious infectious diseases (uncured pulmonary tuberculosis, pulmonary aspergillosis,&#xD;
               etc.).&#xD;
  &#xD;
            6. Other uncontrolled malignancies (excluding non Melanoma skin cancer, cervical cancer&#xD;
               in situ, bladder cancer cancer and breast cancer with disease-free survival of more&#xD;
               than 5 years).&#xD;
  &#xD;
            7. Individuals with epilepsy, dementia, and other mental disorders who require medication&#xD;
               treatment and are unable to understand or follow the research protocol.&#xD;
  &#xD;
            8. Drug use, medical, psychological, or social conditions that may interfere with&#xD;
               participants' participation in the study or evaluation of the results.&#xD;
  &#xD;
            9. Pregnant and lactating women.&#xD;
  &#xD;
           10. Patients who are accounted to be not appropriate for this trail by 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>Juan Du, Doctor</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shanghai Changzheng Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Haiyan He, Master</last_name>
      <phone>+8613661513012</phone>
      <email>doctorhehaiyan@126.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shanghai Changzheng Hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200020</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Juan Du, Doctor</last_name>
        <phone>+86 02181885424</phone>
        <email>Juan_du@live.com</email>
      </contact>
      <contact_backup>
        <last_name>Haiyan He, Master</last_name>
        <phone>+86 13661513012</phone>
        <email>doctorhehaiyan@126.com</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shanghai Changzheng Hospital</investigator_affiliation>
      <investigator_full_name>Juan Du</investigator_full_name>
      <investigator_title>Director</investigator_title>
    </responsible_party>
    <keyword>Waldenström's macroglobulinemia</keyword>
    <keyword>Zanubrutinib</keyword>
    <keyword>BR regimen</keyword>
    <keyword>newly-diagnosed</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Rituximab</mesh_term>
      <mesh_term>Bendamustine Hydrochloride</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>
  
  
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/NCT05979948
  org study id: CZ-WM01
  nct id: NCT05979948
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This was a single-arm, multicenter, Phase 2 study to evaluate the efficacy of zanubrutinib
        combined with BR (Bendamustine/Rituximab) regimen in Chinese participants with
        newly-diagnosed Waldenström's macroglobulinemia who exhibited one or more of the criteria for
        requiring treatment based on consensus guidelines from the 11th International Workshop on
        Waldenström's Macroglobulinemia (IWWM). The investigators propose this combination will
        improve the deep remission compared to single Zanubrutinib or BR regimen and can be a
        time-limited regimen which will reduce the life-time therapy and benefit the patients.
  The study comprised an initial screening phase (up to 7 days), a single-arm treatment phase,
        and a follow-up phase. Subjects with newly-diagnosed Waldenström's macroglobulinemia can
        participate if all eligibility criteria are met. The participants will receive bendamustine
        and rituximab for 6 28-day cycles. Bendamustine will be given intravenously at 70-90 mg/m2 on
        days 1 and 2 of each cycle. Rituximab will be given on day 1 of each cycle (375 mg/m2
        intravenously), Zanubrutinib will be given orally 160mg Bid per day, up to 12 months. The
        participants with WM will also have disease assessment with Lymph node ultrasound and
        abdominal ultrasound each cource, serum IgM, serum protein electrophoresis (SPE),
        immunofixation (IFA), and viscosity assessments will be measured serially. A bone marrow
        aspiration and biopsy flow cytometry examination will be done before treatment and at
        response assessment at cycle 6 and 12. Durability of response will also be assessed every 3
        months after treatment.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall Response Rate (ORR)
  time frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
  description: ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response
  measure: The best deep response rate
  time frame: Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
  description: defined as complete response (CR) and very good partial response (VGPR)
  measure: Progression-free Survival (PFS)
  time frame: Up to 6 years post first dose
  description: PFS was defined as from the initiation of treatmentuntil to first documentation of progression or death, whichever comes first.
  measure: Overall Survival (OS)
  time frame: Up to 6 years post first dose
  description: OS is measured from the date of the initial of treatment to the date of the subject's death.
  measure: minimal residual disease (MRD) rate
  time frame: Up to 6 years post first dose
  description: MRD will be assessed at two on treatment timepoints (before start of cycles 7, 12) and every 6 months thereafter. MRD will be measured through bone marrow samples using flow cytometrey.
  arm group label: zanubrutinib combined with BR regimen
  arm group type: Experimental
  description: Drug: zanubrutinib,160 mg oral capsules twice daily for 12 months Drug: Bendamustine,70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles. Drug: Rituximab,375 mg/m2 intravenously on day 0 of each cycle for 6 cycles.
  intervention type: Drug
  intervention name: Zanubrutinib
  description: Zanubrutinib, 160 mg oral capsules twice daily for 12 months
  arm group label: zanubrutinib combined with BR regimen
  intervention type: Drug
  intervention name: Bendamustine
  description: Bendamustine, 70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles.
  arm group label: zanubrutinib combined with BR regimen
  intervention type: Drug
  intervention name: Rituximab
  description: Rituximab, 375 mg/m2 intravenously on day 0 of each cycle for 6 cycles
  arm group label: zanubrutinib combined with BR regimen
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Juan Du, Doctor
  role: Principal Investigator
  affiliation: Shanghai Changzheng Hospital
  last name: Haiyan He, Master
  phone: +8613661513012
  email: doctorhehaiyan@126.com
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Shanghai Changzheng Hospital
  investigator full name: Juan Du
  investigator title: Director
  mesh term: Waldenstrom Macroglobulinemia
  mesh term: Rituximab
  mesh term: Bendamustine Hydrochloride
  mesh term: Zanubrutinib
  sharing ipd: No