<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/NCT02987127</url>
  </required_header>
  <id_info>
    <org_study_id>201511025MINC</org_study_id>
    <nct_id>NCT02987127</nct_id>
  </id_info>
  <brief_title>Prospective Study of Frontline H Pylori Eradication in the Treatment of Early-stage Extragastric MALT Lymphoma</brief_title>
  <official_title>Prospective Study of Frontline Helicobacter Pylori Eradication Therapy in the Treatment of Early-stage Extragastric Mucosa-associated Lymphoid Tissue Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gastric low-grade mucosa-associated lymphoid tissue lymphoma (MALToma) is associated with&#xD;
      Helicobacter pylori (HP) infection, and around 70% of these tumors can be cured by HP&#xD;
      eradication therapy (HPE). However, the role of antibiotics in the frontline treatment of&#xD;
      extragastric MALToma remains unclear. In addition to anecdotal case reports showing&#xD;
      histologic regression of extragastric MALTomas after antibiotics, our explorative study found&#xD;
      that frontline HPE (clarithromycin, amoxicillin, and omeprazole) resulted in complete&#xD;
      remission (CR) in this subgroup patients (2 salivary gland, 1 lung, 1 colon, and 4 ocular&#xD;
      adnexal MALToma [OAML]). Interestingly, two patients with OAML who do not respond to&#xD;
      Chlamydia psittaci (CP) eradication using doxycycline achieved CR after HPE. These findings&#xD;
      suggest that bacterial infections, including HP, may be involved in the lymphomagenesis of&#xD;
      these extragastric MALTomas. Our preliminary results also revealed that 5 (23.8%) of 21&#xD;
      HP-negative gastric MALToma patients achieved CR after HPE, indicating that antibiotics may&#xD;
      also have ability to eradicate non-HP bacteria. Based on our preliminary findings and the&#xD;
      indolent biologic behavior of MALToma, it is reasonable to use frontline HPE in the treatment&#xD;
      of early-stage low-grade extragastric MALToma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Through a prospective trial of frontline HPE in the treatment of early-stage extragastric&#xD;
      MALToma, investigators will evaluate and investigate the following issues:&#xD;
&#xD;
        1. The CR and partial remission (PR) rate for antibiotics as 1st-line therapy for stage IE&#xD;
           and stage IIE extragastric MALToma&#xD;
&#xD;
        2. The durability of CR and PR (relapse-free survival) after antibiotics treatment (HPE) in&#xD;
           early-stage extragastric MALToma&#xD;
&#xD;
        3. The assessment of the evidence of bacterial infection, such as HP, in extragastric&#xD;
           MALToma.&#xD;
&#xD;
        4. The identification of potential biomarkers that help us predict whether extragastric&#xD;
           MALToma can respond to frontline HPE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>February 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">September 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The complete and partial remission rate for antibiotics as 1st-line therapy for stage IE-IIE1 extragastric MALT lymphoma.</measure>
    <time_frame>5 years</time_frame>
    <description>The complete remission rate and partial remission rate for antibiotics (HP eradicaiton) as 1st-line therapy for early-stage extragastric MALT lymphoma</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The overall survival of early-stage extragastric MALT lymphoma patients who received frontline HP eradication therapy</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The assessment of the evidence of bacterial infection in all extragstric MALT lymphoma</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The usefulness of pattern of NF-κB, BCL10, BAFF, API2-MALT1, and IgH-MALT1 by IHC staining or FISH in prospectively predicting the antibiotics responsiveness of extragastric MALT lymphoma</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The relapse-free survival of early-stage extragastric MALT lymphoma patients who received antibiotics as 1st-line therapy</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>The complete remission rate and durability of second-line chemotherapy with chlorambucil plus prednisolone for progressive disease after frontline HP eradication therapy</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <enrollment type="Anticipated">21</enrollment>
  <condition>Mucosa-Associated Lymphoid Tissue Lymphoma</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Extragastric mucosa-associated lymphoid tissue lymphoma&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patients must have histologically confirmed low-grade mucosa-associated&#xD;
&#xD;
          2. lymphoid tissue lymphoma of extragastric sites.&#xD;
&#xD;
          3. Patients must have evaluable disease by physical examination, endoscopy (also include&#xD;
             colonfibroscopy, and bronchoscopy) or computed tomography.&#xD;
&#xD;
          4. Patients must receive examination of documented HP infection or not before treatment,&#xD;
             which will be evaluated by the following tests: histology, rapid urease test&#xD;
             (CLO-test), C-13 urease breath test and serology.&#xD;
&#xD;
          5. Patients must have either stage IE or IIE-1 disease, according to an adaptation of the&#xD;
             Ann Arbor staging system modified by Musshoff for primary extranodal lymphoma.&#xD;
&#xD;
          6. Patients must have signed the informed consent and agree to provide achieved&#xD;
             pathologic material for immunohistochemical staining of BCL10, NF-KB, BAFF, CagA,&#xD;
             CagA-signaling molecules, for fluorescence in situ hybridization study for&#xD;
             t(11;18)(q21;q21)/API2-MALT1 and t(14;18)(q32;q21)/IGH-MALT1 determination, and for&#xD;
             PCR of Chlamydia psittaci and Borrelia burgdorferi.&#xD;
&#xD;
          7. Patients must have signed the informed consent and agree to provide achieve blood&#xD;
             samples for CYP2C19 genetic polymorphisms evaluation and potential serum molecular&#xD;
             studies, such as serum BAFF level&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. In the diagnosis of the disease over the past five years with a history of other&#xD;
             cancers but non-melanoma skin cancer, breast and cervical carcinoma in situ carcinoma&#xD;
             in situ (leafy or tubular) can still meet the conditions of admission to this case&#xD;
             study&#xD;
&#xD;
          2. Patients receiving chemotherapy or radiotherapy of nodules outside the low-grade&#xD;
             malignant lymphoma, but has not yet been cured, the excluded&#xD;
&#xD;
          3. The second more, and not in the lymph nodes adjacent to the tumor (IIE-2 period or&#xD;
             more), the excluded&#xD;
&#xD;
          4. The state can not afford this clinical cardiopulmonary ㄧ inspection after the test&#xD;
             series, the excluded&#xD;
&#xD;
          5. suffering from primary gastric outside MALToma before and had received chemotherapy or&#xD;
             radiation therapy in patients of.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sung-Hsin Kuo, M.D.,Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sung-Hsin Kuo, M.D.,Ph.D</last_name>
    <phone>+886-2-23123456</phone>
    <phone_ext>67144</phone_ext>
    <email>shkuo101@ntu.edu.tw</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Shu-Ling Wu, MS</last_name>
    <phone>+886-2-23123456</phone>
    <phone_ext>67573</phone_ext>
    <email>shulingwu.ntuh@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sung-Hsin Kuo, M.D.,Ph.D</last_name>
      <phone>+886-2-23123456</phone>
      <phone_ext>67144</phone_ext>
      <email>shkuo101@ntu.edu.tw</email>
    </contact>
    <contact_backup>
      <last_name>Shu-Ling Wu, MS</last_name>
      <phone>+886-2-23123456</phone>
      <phone_ext>67573</phone_ext>
      <email>shulingwu.ntuh@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>December 6, 2016</last_update_submitted>
  <last_update_submitted_qc>December 6, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 8, 2016</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, Marginal Zone</mesh_term>
  </condition_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/NCT02987127
org study id: 201511025MINC
nct id: NCT02987127
lead sponsor: 
has dmc: No
Gastric low-grade mucosa-associated lymphoid tissue lymphoma (MALToma) is associated with
      Helicobacter pylori (HP) infection, and around 70% of these tumors can be cured by HP
      eradication therapy (HPE). However, the role of antibiotics in the frontline treatment of
      extragastric MALToma remains unclear. In addition to anecdotal case reports showing
      histologic regression of extragastric MALTomas after antibiotics, our explorative study found
      that frontline HPE (clarithromycin, amoxicillin, and omeprazole) resulted in complete
      remission (CR) in this subgroup patients (2 salivary gland, 1 lung, 1 colon, and 4 ocular
      adnexal MALToma [OAML]). Interestingly, two patients with OAML who do not respond to
      Chlamydia psittaci (CP) eradication using doxycycline achieved CR after HPE. These findings
      suggest that bacterial infections, including HP, may be involved in the lymphomagenesis of
      these extragastric MALTomas. Our preliminary results also revealed that 5 (23.8%) of 21
      HP-negative gastric MALToma patients achieved CR after HPE, indicating that antibiotics may
      also have ability to eradicate non-HP bacteria. Based on our preliminary findings and the
      indolent biologic behavior of MALToma, it is reasonable to use frontline HPE in the treatment
      of early-stage low-grade extragastric MALToma.
Through a prospective trial of frontline HPE in the treatment of early-stage extragastric
      MALToma, investigators will evaluate and investigate the following issues:

        1. The CR and partial remission (PR) rate for antibiotics as 1st-line therapy for stage IE
           and stage IIE extragastric MALToma

        2. The durability of CR and PR (relapse-free survival) after antibiotics treatment (HPE) in
           early-stage extragastric MALToma

        3. The assessment of the evidence of bacterial infection, such as HP, in extragastric
           MALToma.

        4. The identification of potential biomarkers that help us predict whether extragastric
           MALToma can respond to frontline HPE.
observational model: Case-Only
time perspective: Prospective
measure: The complete and partial remission rate for antibiotics as 1st-line therapy for stage IE-IIE1 extragastric MALT lymphoma.
time frame: 5 years
description: The complete remission rate and partial remission rate for antibiotics (HP eradicaiton) as 1st-line therapy for early-stage extragastric MALT lymphoma
measure: The overall survival of early-stage extragastric MALT lymphoma patients who received frontline HP eradication therapy
time frame: 5 years
measure: The assessment of the evidence of bacterial infection in all extragstric MALT lymphoma
time frame: 5 years
measure: The usefulness of pattern of NF-κB, BCL10, BAFF, API2-MALT1, and IgH-MALT1 by IHC staining or FISH in prospectively predicting the antibiotics responsiveness of extragastric MALT lymphoma
time frame: 5 years
measure: The relapse-free survival of early-stage extragastric MALT lymphoma patients who received antibiotics as 1st-line therapy
time frame: 5 years
measure: The complete remission rate and durability of second-line chemotherapy with chlorambucil plus prednisolone for progressive disease after frontline HP eradication therapy
time frame: 5 years
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Sung-Hsin Kuo, M.D.,Ph.D
role: Principal Investigator
affiliation: National Taiwan University Hospital
last name: Sung-Hsin Kuo, M.D.,Ph.D
phone: +886-2-23123456
phone ext: 67144
email: shkuo101@ntu.edu.tw
last name: Shu-Ling Wu, MS
phone: +886-2-23123456
phone ext: 67573
email: shulingwu.ntuh@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Taiwan
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell, Marginal Zone
sharing ipd: No