<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/NCT04433156</url>
  </required_header>
  <id_info>
    <org_study_id>HNSZLYYNHL03</org_study_id>
    <nct_id>NCT04433156</nct_id>
  </id_info>
  <brief_title>VR-CAP in the First-line Treatment for Patients With Marginal Zone Lymphoma</brief_title>
  <official_title>A Single Arm, Multi-center, Phase II Clinical Trial of VR-CAP in the First-line Treatment for Patients With Marginal Zone Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Henan Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Henan Cancer 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 arm, multi-center, phase II clinical trial to observe the&#xD;
      efficacy and safety of VR-CAP (Bortezomib and Rituximab-Cyclophosphamide, Epirubicin and&#xD;
      Prednisone) in the first-line treatment for patients with marginal zone lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Marginal zone lymphoma (MZL) is a relatively common group of non-Hodgkin's lymphoma (NHL).&#xD;
      The incidence rate is only inferior to diffuse large B cell lymphoma (DLBCL) and follicular&#xD;
      lymphoma (FL). Currently, NCCN guidelines recommend same treatment plan of FL like R-CHOP as&#xD;
      the primary treatment for MZL. However, due to the great difference in cell origin and&#xD;
      biological characteristics between FL and MZL, some patients can not achieve complete&#xD;
      remission or relapse quickly after standard first-line treatment. A number of phase II&#xD;
      clinical studies have evaluated the good efficacy of rituximab combined with chemotherapy in&#xD;
      the treatment of MZL. Previous studies have shown that NF-κB signaling pathway is in abnormal&#xD;
      activation state in MZL. Bortezomib, a proteasome inhibitor targeting NF-κB pathway, has a&#xD;
      promising therapeutic prospect in relapsed and refractory MZL. The goal of our trial is to&#xD;
      assess the efficacy and safety of VR-CAP (Bortezomib and Rituximab-Cyclophosphamide,&#xD;
      Epirubicin and Prednisone) in the first-line treatment for patients with marginal zone&#xD;
      lymphoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 22, 2020</start_date>
  <completion_date type="Anticipated">April 22, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>2-year progression-free survival</measure>
    <time_frame>from the beginning day of the first cycle (each cycle is 21 days) of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment</time_frame>
    <description>the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurs first</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>objective response rate</measure>
    <time_frame>every 6 weeks from the beginning day of the first cycle (each cycle is 21 days) of induction chemotherapy treatment and every 8 weeks from the day of the first cycle of maintenance treatment to 18 months after last patient's enrollment</time_frame>
    <description>the total proportion of patients with complete response (CR) and partial response (PR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>from the beginning day of the first cycle (each cycle is 21 days) of treatment to the date of death from any cause, assessed up to 5 years</time_frame>
    <description>from date of first day of treatment to the date of death by any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence and relationship with study drugs of grade 3-4 adverse events</measure>
    <time_frame>from the beginning day of the first cycle (each cycle is 21 days) of treatment to 6 months after last patient's enrollment</time_frame>
    <description>the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Marginal Zone Lymphoma</condition>
  <arm_group>
    <arm_group_label>VR-CAP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rituximab, 375 mg/m2, Intravenous administration on day 0, Bortezomib, 1.3 mg/m2 hypodermic injection on day 1 and 4, combined with regimen: Cyclophosphamide, Epirubicin, and Prednisone: repeated every 3 weeks, up to 6 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>1.3 mg/m2, hypodermic injection on day 1 and day 4 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.</description>
    <arm_group_label>VR-CAP</arm_group_label>
    <other_name>Bortezomib Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>375 mg/m2, Intravenous administration on day 0 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.</description>
    <arm_group_label>VR-CAP</arm_group_label>
    <other_name>RiTUXimab Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <description>70 mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.</description>
    <arm_group_label>VR-CAP</arm_group_label>
    <other_name>Epirubicin hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>750 mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.</description>
    <arm_group_label>VR-CAP</arm_group_label>
    <other_name>Cyclophosphamide Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles</description>
    <arm_group_label>VR-CAP</arm_group_label>
    <other_name>Prednisone Oral Product</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age between 18 to 70 years old (including 18 and 70)&#xD;
&#xD;
          2. Diagnosed as marginal zone lymphoma&#xD;
&#xD;
          3. No receiving chemotherapy before enrollment&#xD;
&#xD;
          4. Indications for treatment: 1) symptoms related to tumor; 2) end-organ function damage;&#xD;
             3) large mass; 4) continuous or rapid progress of disease; 5) patient's willingness&#xD;
&#xD;
          5. Having at least one measurable lesions&#xD;
&#xD;
          6. World health organization-Eastern Cooperative Oncology Group Performance tatus (ECOG)&#xD;
             0-1&#xD;
&#xD;
          7. Life expectancy no less than 3 months&#xD;
&#xD;
          8. enough main organ function&#xD;
&#xD;
          9. Pregnancy test within 7 days must be negative for women of childbearing period, and&#xD;
             appropriate measures should be taken for contraception for women in childbearing&#xD;
             period during the study and six months after this study&#xD;
&#xD;
         10. Agreeing to sign the written informed consents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosed as central nervous system lymphoma&#xD;
&#xD;
          2. World health organization-Eastern Cooperative Oncology Group Performance tatus (ECOG)&#xD;
             ≥2&#xD;
&#xD;
          3. Other malignant tumor history or active malignant tumor need be treated&#xD;
&#xD;
          4. Serious surgery and trauma less than two weeks&#xD;
&#xD;
          5. Systemic therapy for serious acute/chronic infection&#xD;
&#xD;
          6. Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart&#xD;
             infarction less than 6 months&#xD;
&#xD;
          7. Active tuberculosis. Patients suspected of active TB need to be examined for chest&#xD;
             X-ray, sputum and clinical symptoms and signs&#xD;
&#xD;
          8. HIV-positive, AIDS patients and untreated active hepatitis（HBV/HBV and HCV）&#xD;
&#xD;
          9. Patients with a history of deep vein thrombosis or pulmonary embolism less than 12&#xD;
             months&#xD;
&#xD;
         10. Patients with a history of mental illness&#xD;
&#xD;
         11. Researchers determine unsuited to participate in this trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yanyan Liu, M.D. Ph.D</last_name>
    <role>Study Director</role>
    <affiliation>Henan Cancer Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yanyan Liu, M.D. Ph.D</last_name>
    <phone>+8613818176375</phone>
    <email>yyliu@zzu.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yanyan Liu, M.D. Ph.D</last_name>
      <phone>+8613818176375</phone>
      <email>yyliu@zzu.edu.cn</email>
    </contact>
    <investigator>
      <last_name>Yanyan Liu, M.D. Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>May 17, 2023</last_update_submitted>
  <last_update_submitted_qc>May 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Henan Cancer Hospital</investigator_affiliation>
    <investigator_full_name>Yanyan Liu</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>Marginal Zone Lymphoma</keyword>
  <keyword>VR-CAP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
    <mesh_term>Epirubicin</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/NCT04433156
org study id: HNSZLYYNHL03
nct id: NCT04433156
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective single arm, multi-center, phase II clinical trial to observe the
      efficacy and safety of VR-CAP (Bortezomib and Rituximab-Cyclophosphamide, Epirubicin and
      Prednisone) in the first-line treatment for patients with marginal zone lymphoma.
Marginal zone lymphoma (MZL) is a relatively common group of non-Hodgkin's lymphoma (NHL).
      The incidence rate is only inferior to diffuse large B cell lymphoma (DLBCL) and follicular
      lymphoma (FL). Currently, NCCN guidelines recommend same treatment plan of FL like R-CHOP as
      the primary treatment for MZL. However, due to the great difference in cell origin and
      biological characteristics between FL and MZL, some patients can not achieve complete
      remission or relapse quickly after standard first-line treatment. A number of phase II
      clinical studies have evaluated the good efficacy of rituximab combined with chemotherapy in
      the treatment of MZL. Previous studies have shown that NF-κB signaling pathway is in abnormal
      activation state in MZL. Bortezomib, a proteasome inhibitor targeting NF-κB pathway, has a
      promising therapeutic prospect in relapsed and refractory MZL. The goal of our trial is to
      assess the efficacy and safety of VR-CAP (Bortezomib and Rituximab-Cyclophosphamide,
      Epirubicin and Prednisone) in the first-line treatment for patients with marginal zone
      lymphoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 2-year progression-free survival
time frame: from the beginning day of the first cycle (each cycle is 21 days) of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment
description: the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurs first
measure: objective response rate
time frame: every 6 weeks from the beginning day of the first cycle (each cycle is 21 days) of induction chemotherapy treatment and every 8 weeks from the day of the first cycle of maintenance treatment to 18 months after last patient's enrollment
description: the total proportion of patients with complete response (CR) and partial response (PR)
measure: overall survival
time frame: from the beginning day of the first cycle (each cycle is 21 days) of treatment to the date of death from any cause, assessed up to 5 years
description: from date of first day of treatment to the date of death by any cause
measure: incidence and relationship with study drugs of grade 3-4 adverse events
time frame: from the beginning day of the first cycle (each cycle is 21 days) of treatment to 6 months after last patient's enrollment
description: the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03
arm group label: VR-CAP
arm group type: Experimental
description: Rituximab, 375 mg/m2, Intravenous administration on day 0, Bortezomib, 1.3 mg/m2 hypodermic injection on day 1 and 4, combined with regimen: Cyclophosphamide, Epirubicin, and Prednisone: repeated every 3 weeks, up to 6 cycles.
intervention type: Drug
intervention name: Bortezomib
description: 1.3 mg/m2, hypodermic injection on day 1 and day 4 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
arm group label: VR-CAP
other name: Bortezomib Injection
intervention type: Drug
intervention name: Rituximab
description: 375 mg/m2, Intravenous administration on day 0 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
arm group label: VR-CAP
other name: RiTUXimab Injection
intervention type: Drug
intervention name: Epirubicin
description: 70 mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
arm group label: VR-CAP
other name: Epirubicin hydrochloride
intervention type: Drug
intervention name: Cyclophosphamide
description: 750 mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
arm group label: VR-CAP
other name: Cyclophosphamide Injection
intervention type: Drug
intervention name: Prednisone
description: 100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles
arm group label: VR-CAP
other name: Prednisone Oral Product
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yanyan Liu, M.D. Ph.D
role: Study Director
affiliation: Henan Cancer Hospital
last name: Yanyan Liu, M.D. Ph.D
phone: +8613818176375
email: yyliu@zzu.edu.cn
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Henan Cancer Hospital
investigator full name: Yanyan Liu
investigator title: Director
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Bortezomib
mesh term: Epirubicin
sharing ipd: No