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/NCT05992597</url>
    </required_header>
    <id_info>
      <org_study_id>ZR2 + RDHAP</org_study_id>
      <nct_id>NCT05992597</nct_id>
    </id_info>
    <brief_title>ZR2 Sequential Immunochemotherapy for Newly Treated MCL</brief_title>
    <official_title>Prospective, Single-arm, Single-center, Phase II Clinical Study of Rituximab, Lenalidomide, Zebutinib Combined Regimen Followed by Sequential Immunochemotherapy in the Treatment of Initially Treated Mantle Cell Lymphoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhejiang Cancer Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Zhejiang Cancer Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Patients with newly diagnosed MCL were treated with ZR2 regimen for 3 cycles, followed by 3&#xD;
        cycles of immunochemotherapy, and zebrutinib maintenance therapy for 2 years after the end of&#xD;
        induction therapy, in order to improve the remission rate and prognosis of patients with&#xD;
        induction therapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        his is a prospective, single-arm, multicenter, Phase II clinical study evaluating sequential&#xD;
        immunochemotherapy followed by rituximab, lenalidomide, and zebutinib combined with or&#xD;
        without autologous hematopoietic stem cell transplantation followed by zebutinib maintenance&#xD;
        therapy for initial treatment of capsular cell lymphoma. There are three stages: screening,&#xD;
        treatment and follow-up. The screening period was 28 days before the first administration.&#xD;
        Treatment period: Enrolled subjects first received 3 cycles of rituximab, lenalidomide,&#xD;
        zebutinib without chemotherapy (21 days for one cycle), followed by 3 cycles of RDHAP&#xD;
        immunochemotherapy (21 days for one cycle); All patients were assessed with interim Positron&#xD;
        Emission Tomography (iPET) after 3 cycles of rituximab, lenalidomide, and zebutinib without&#xD;
        chemotherapy. All patients will continue to receive 3 cycles Of RDHAP, followed by Treatment&#xD;
        End Of Positron Emission Tomography. For patients who have achieved complete metabolic&#xD;
        response (CMR) or partial metabolic response (PMR), autologous hematopoietic stem cell&#xD;
        transplantation (ASCT) can be performed as consolidation therapy after the researchers&#xD;
        evaluate their physical status and their personal wishes. 3 months after ASCT, PET will be&#xD;
        reviewed for efficacy evaluation after transplantation. Zebutinib maintenance therapy was&#xD;
        started 2 months after transplantation for 2 years. For patients without ASCT, zebutinib&#xD;
        maintenance therapy was started directly for 2 years. The follow-up period was entered after&#xD;
        the end of maintenance therapy. Efficacy was evaluated using Lugano2014 criteria. Patients&#xD;
        with disease progression during non-chemotherapy treatment were directly entered into RDHAP&#xD;
        immunochemotherapy, and patients with disease progression during immunochemotherapy were&#xD;
        directly removed from the group and entered second-line treatment. Objective effective rate,&#xD;
        safety index and survival data of patients were observed during the experiment. Subjects will&#xD;
        enter the follow-up period after the study treatment is discontinued or the treatment period&#xD;
        has been completed.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2022</start_date>
    <completion_date type="Anticipated">December 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 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>ORR</measure>
      <time_frame>Time Frame: 21days after the end of treatment</time_frame>
      <description>overall response rate</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>PFS</measure>
      <time_frame>Time Frame: From date of first day of treatment until the date of first documented progression, assessed up to 24 months</time_frame>
      <description>Progression Free Survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS</measure>
      <time_frame>Time Frame: From date of first day of treatment until the date of first documented date of death from any cause, assessed up to 24 months</time_frame>
      <description>Overall Survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AE and SAE</measure>
      <time_frame>Time Frame: From date of first day of treatment until 30 day after last treatment</time_frame>
      <description>Adverse event and serious adverse event</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">48</enrollment>
    <condition>Rituximab, Lenalidomide, Zebutinib ，Mantle Cell Lymphoma</condition>
    <arm_group>
      <arm_group_label>rituximab, lenalidomide, and zebutinib,RDHAP</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ZR2 RDHAP</intervention_name>
      <description>ZR2:Rituximab 375mg/m2, D1, Lenalidomide 24mg qd D1-14, zebutinib 160mg bid RDHAP:Rituximab 375mg/m2 D0, dexamethasone 40mg D1-4, cytarabine 2g/m2 q12h D2, cisplatin 25mg/m2 D1-3.</description>
      <arm_group_label>rituximab, lenalidomide, and zebutinib,RDHAP</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Participate in the clinical study voluntarily: fully understand and be informed of the&#xD;
               study and sign the informed consent in person; Willing to follow and be able to&#xD;
               complete all test procedures.&#xD;
  &#xD;
            2. 18~75 years old (inclusive), male and female.&#xD;
  &#xD;
            3. histopathologically confirmed mantle cell lymphoma, including positive&#xD;
               immunohistochemical CyclinD1 (CyclinD1 or CCND1) and/or chromosomal t (11; 14) (q13;&#xD;
               Q32) ectopic.&#xD;
  &#xD;
            4. No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or&#xD;
               biotherapy (tumor vaccine, cytokine, or growth factor controlling cancer).&#xD;
  &#xD;
            5. there must be at least one evaluable or measurable lesion that meets Lugano2014&#xD;
               criteria (evaluable lesion: PET/CT examination showing increased uptake in lymph nodes&#xD;
               or extratodal areas (higher than liver) and PET/CT and/or CT features consistent with&#xD;
               lymphoma; Measurable lesions: nodular lesions &gt;15mm in length or extragendal lesions&#xD;
               &gt;10mm in length with increased FDG uptake).&#xD;
  &#xD;
            6. Adequate organ and bone marrow function, no serious hematopoietic dysfunction,&#xD;
               abnormal heart, lung, liver, kidney function and immune deficiency (no blood&#xD;
               transfusion, granulocytic colony stimulating factor or other relevant medical support&#xD;
               within 14 days prior to the use of the study drug) :&#xD;
  &#xD;
               A) Blood routine: neutrophil absolute count (ANC) ≥1.5×109/L (1500/mm3), platelet&#xD;
               ≥75×109/L, hemoglobin ≥100g/L (if bone marrow is involved, platelet ≥50×109/L, ANC&#xD;
               ≥1.0×109/L, hemoglobin ≥80g/L).&#xD;
  &#xD;
               B) Liver function: serum bilirubin ≤2.5 times the upper limit of normal value,&#xD;
               aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 times the&#xD;
               upper limit of normal value (AST is allowed if liver is involved, ALT≤5 times the&#xD;
               upper limit of normal value).&#xD;
  &#xD;
               C) Renal function: creatinine clearance ≥60 mL/min (estimated according to the&#xD;
               Cockcroft-Gault formula).&#xD;
  &#xD;
               D) Coagulation function: INR≤1.5 times the upper limit of normal value; PT and&#xD;
               APTT≤1.5 times the upper limit of normal value.&#xD;
  &#xD;
            7. Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination.&#xD;
  &#xD;
            8. Male subjects used effective contraception from signing informed consent until 6&#xD;
               months after the last chemotherapy.&#xD;
  &#xD;
            9. Life expectancy &gt; 3 months.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. The diagnosis was leukemic mantle cell lymphoma.&#xD;
  &#xD;
            2. Central nervous system involvement secondary to lymphoma.&#xD;
  &#xD;
            3. history of other active malignant diseases within 2 years prior to study entry, but&#xD;
               eligibility for inclusion :(1) adequately treated carcinoma in situ of the cervix; (2)&#xD;
               local basal cell carcinoma or squamous cell carcinoma of skin; (3) Pre-existing&#xD;
               malignant disease that is under control and has undergone local radical treatment&#xD;
               (surgical or other forms).&#xD;
  &#xD;
            4. People with a known history of Human Immunodeficiency Virus (HIV) infection and/or&#xD;
               acquired Immunodeficiency syndrome. Screening stage of hepatitis b surface antigen or&#xD;
               hepatitis c virus antibody positive patients, must further by hepatitis b virus DNA&#xD;
               (no more than 1000 iu/ml) and HCV RNA detection (shall not exceed the method detection&#xD;
               limit), in the activity of the ruled out the need for treatment after hepatitis b or&#xD;
               hepatitis c infection, before the experiment. Patients with hepatitis B virus&#xD;
               carriers, stabilized hepatitis B after drug treatment and cured hepatitis C can be&#xD;
               included.&#xD;
  &#xD;
          (5) Major surgery was performed within 28 days prior to study initiation. 6) Any active&#xD;
          infections, including but not limited to bacterial, fungal or viral infections, that&#xD;
          require systemic antiinfective therapy within 14 days prior to initiation of treatment.&#xD;
  &#xD;
          7) combined with severe or uncontrolled disease, including but not limited to symptomatic&#xD;
          of congestive heart failure, uncontrolled hypertension, unstable angina, active peptic&#xD;
          ulcer or A history of severe hemorrhagic diseases, such as hemophilia a., hemophilia B, von&#xD;
          willebrand disease or blood transfusion or other medical intervention history of&#xD;
          spontaneous bleeding.&#xD;
  &#xD;
          8) History of stroke or intracranial hemorrhage within 6 months prior to first&#xD;
          administration of the study drug.&#xD;
  &#xD;
          9) A history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12&#xD;
          months.&#xD;
  &#xD;
          10) Patients who must take antiplatelet drugs and anticoagulant drugs at the same time due&#xD;
          to underlying diseases and have no alternative treatment plan.&#xD;
  &#xD;
          11) Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is&#xD;
          required. Patients were excluded if they had taken a CYP3A potent or moderate-acting&#xD;
          inhibitor or inducer within 7 days prior to the first administration of the study drug (or&#xD;
          had taken these drugs for less than 5 half-lives).&#xD;
  &#xD;
          12) Patients deemed unsuitable for the study by other investigators.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Zhejiang Cancer Hospital</name>
        <address>
          <city>Hangzhou</city>
          <state>Zhejiang</state>
          <zip>310022</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Haiyan Yang, PhD</last_name>
        <phone>0086-571-88122192</phone>
        <email>yanghy@zjcc.org.cn</email>
      </contact>
      <contact_backup>
        <last_name>Xi Chen, MD</last_name>
        <phone>0086-571-88122192</phone>
        <email>zjuchenxi@126.com</email>
      </contact_backup>
      <investigator>
        <last_name>Xi Chen, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Zhejiang Cancer Hospital</investigator_affiliation>
      <investigator_full_name>Yang haiyan</investigator_full_name>
      <investigator_title>MD</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, Mantle-Cell</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/NCT05992597
  org study id: ZR2 + RDHAP
  nct id: NCT05992597
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Patients with newly diagnosed MCL were treated with ZR2 regimen for 3 cycles, followed by 3
        cycles of immunochemotherapy, and zebrutinib maintenance therapy for 2 years after the end of
        induction therapy, in order to improve the remission rate and prognosis of patients with
        induction therapy.
  his is a prospective, single-arm, multicenter, Phase II clinical study evaluating sequential
        immunochemotherapy followed by rituximab, lenalidomide, and zebutinib combined with or
        without autologous hematopoietic stem cell transplantation followed by zebutinib maintenance
        therapy for initial treatment of capsular cell lymphoma. There are three stages: screening,
        treatment and follow-up. The screening period was 28 days before the first administration.
        Treatment period: Enrolled subjects first received 3 cycles of rituximab, lenalidomide,
        zebutinib without chemotherapy (21 days for one cycle), followed by 3 cycles of RDHAP
        immunochemotherapy (21 days for one cycle); All patients were assessed with interim Positron
        Emission Tomography (iPET) after 3 cycles of rituximab, lenalidomide, and zebutinib without
        chemotherapy. All patients will continue to receive 3 cycles Of RDHAP, followed by Treatment
        End Of Positron Emission Tomography. For patients who have achieved complete metabolic
        response (CMR) or partial metabolic response (PMR), autologous hematopoietic stem cell
        transplantation (ASCT) can be performed as consolidation therapy after the researchers
        evaluate their physical status and their personal wishes. 3 months after ASCT, PET will be
        reviewed for efficacy evaluation after transplantation. Zebutinib maintenance therapy was
        started 2 months after transplantation for 2 years. For patients without ASCT, zebutinib
        maintenance therapy was started directly for 2 years. The follow-up period was entered after
        the end of maintenance therapy. Efficacy was evaluated using Lugano2014 criteria. Patients
        with disease progression during non-chemotherapy treatment were directly entered into RDHAP
        immunochemotherapy, and patients with disease progression during immunochemotherapy were
        directly removed from the group and entered second-line treatment. Objective effective rate,
        safety index and survival data of patients were observed during the experiment. Subjects will
        enter the follow-up period after the study treatment is discontinued or the treatment period
        has been completed.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: ORR
  time frame: Time Frame: 21days after the end of treatment
  description: overall response rate
  measure: PFS
  time frame: Time Frame: From date of first day of treatment until the date of first documented progression, assessed up to 24 months
  description: Progression Free Survival
  measure: OS
  time frame: Time Frame: From date of first day of treatment until the date of first documented date of death from any cause, assessed up to 24 months
  description: Overall Survival
  measure: AE and SAE
  time frame: Time Frame: From date of first day of treatment until 30 day after last treatment
  description: Adverse event and serious adverse event
  arm group label: rituximab, lenalidomide, and zebutinib,RDHAP
  arm group type: Experimental
  intervention type: Drug
  intervention name: ZR2 RDHAP
  description: ZR2:Rituximab 375mg/m2, D1, Lenalidomide 24mg qd D1-14, zebutinib 160mg bid RDHAP:Rituximab 375mg/m2 D0, dexamethasone 40mg D1-4, cytarabine 2g/m2 q12h D2, cisplatin 25mg/m2 D1-3.
  arm group label: rituximab, lenalidomide, and zebutinib,RDHAP
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Zhejiang Cancer Hospital
  investigator full name: Yang haiyan
  investigator title: MD
  mesh term: Lymphoma
  mesh term: Lymphoma, Mantle-Cell
  sharing ipd: No