<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/NCT03031483</url>
  </required_header>
  <id_info>
    <org_study_id>IELSG40</org_study_id>
    <nct_id>NCT03031483</nct_id>
  </id_info>
  <brief_title>Clarithromycin + Lenalidomide Combination: a Full Oral Treatment for Patients With Relapsed/Refractory Extranodal Marginal Zone Lymphoma</brief_title>
  <official_title>A Phase II Trial Addressing Feasibility and Activity of Clarithromycin + Lenalidomide Combination: a Full Oral Treatment for Patients With Relapsed/Refractory Extranodal Marginal Zone Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Extranodal Lymphoma Study Group (IELSG)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>International Extranodal Lymphoma Study Group (IELSG)</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>
      Patients with lymphoid tissue lymphoma mucosa-associated (MALT) for which the standard&#xD;
      treatments with radiotherapy, chemotherapy and / or immunotherapy show lack of efficacy&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 3, 2017</start_date>
  <completion_date type="Anticipated">November 2029</completion_date>
  <primary_completion_date type="Actual">November 13, 2019</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>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Tumor response assessment</measure>
    <time_frame>During the active treatment period after the 3rd cycles of both drugs administration</time_frame>
    <description>The primary outcome measure is tumour response assessed according to the Revised Response Criteria for Malignant Lymphoma, either clinically (including appropriate imaging procedures) or endoscopically and histologically (in patients affected by gastric lymphoma, according to the GELA scoring system).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events assessments</measure>
    <time_frame>During the active treatment period</time_frame>
    <description>Treatment-emergent adverse events (AEs) incidence, severity and relationship to study treatment.&#xD;
Time from first IMP administration to assessment of disease progression or death due to any cause, whichever occurs earlier.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Mucosa Associated Lymphoid Tissue (MALT) Lymphoma</condition>
  <arm_group>
    <arm_group_label>Experimental: clarithromycin and lenalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CLARITHROMYCIN: daily orally administration in cycles of 28 days; 500mg film-coated tablets LENALIDOMIDE: every cycle of treatment lasts 28 days; daily orally administration is of 21 consecutive days with a week of rest. 20mg capsule hard. The maximum treatment duration is 12 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>clarithromycin and lenalidomide</intervention_name>
    <description>Each treatment course will consist of:&#xD;
Oral Lenalidomide (Revlimid) once daily for 21 days at a dose 20 mg; in case of drug-related adverse events the dose can be reduced to 15 and 10 mg/day; Oral Clarithromycin 500 mg twice daily for 28 days. Courses will be repeated every 28 days. After the first 3 courses patients with stable disease or better response will be given another three courses. Patients with complete remission or disease progression after 6 courses will be taken off study, while patients with partial response or stable disease will receive 3 further courses of treatment. Again, patients with complete response or disease progression will stop therapy, while patients with partial response/stable disease will receive 3 further courses up to a maximum of 12 courses in total.</description>
    <arm_group_label>Experimental: clarithromycin and lenalidomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically verified diagnosis of MALT lymphoma arising at any extranodal site&#xD;
&#xD;
          -  Disease refractory to or in first or greater relapse after prior radiotherapy and/ or&#xD;
             chemotherapy and/or immunotherapy&#xD;
&#xD;
          -  Measurable or non-measurable lesions where the response is nevertheless evaluable by&#xD;
             non-imaging means (e.g., gastric or bone marrow infiltrations)&#xD;
&#xD;
          -  Ann Arbor Stage I-IV&#xD;
&#xD;
          -  ECOG performance status of 0, 1 or 2&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
          -  Adequate haematological status: ANC (absolute neutrophil count [segmented + bands])&#xD;
             ≥1.0 x 109/L, platelet count ≥ 75 x 109/L , haemoglobin ≥8 g/dL.&#xD;
&#xD;
          -  Adequate cardiac, renal and liver function tests (LVEF &gt; 40%, serum creatinine &lt; 2.5&#xD;
             mg/dl, ALAT or ASAT &lt; 2.5 x upper limit of normal range, alkaline phosphatase &lt; 2.5 x&#xD;
             upper limit of normal range, serum bilirubin &lt; 2.0 mg/dl)&#xD;
&#xD;
          -  Patient must be willing and able to comply with the protocol for the entire study&#xD;
             duration&#xD;
&#xD;
          -  Female patients of childbearing potential must agree to use, and be able to comply&#xD;
             with, effective contraception and agree to have medically supervised pregnancy tests&#xD;
             prior to starting the study treatment and during therapy&#xD;
&#xD;
          -  Male patients must agree to always use a condom during any sexual contact with females&#xD;
             of reproductive potential and agree to not donate sperm while taking lenalidomide&#xD;
&#xD;
          -  Patient must agree to abstain from donating blood while taking study drug therapy&#xD;
&#xD;
          -  Patient must agree not to share study medication with another person and to return all&#xD;
             unused study drug to the investigator&#xD;
&#xD;
          -  Patient must be willing and able to comply with the protocol&#xD;
&#xD;
          -  Patient must be capable of understanding&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lymphoma histology other than MALT lymphoma or MALT lymphoma with a diffuse large cell&#xD;
             lymphoma (&quot;high grade lymphoma&quot;) component&#xD;
&#xD;
          -  Use of any investigational agent within 28 days prior to initiation of treatment&#xD;
&#xD;
          -  History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the&#xD;
             skin or carcinoma in situ of the uterine cervix within the last 5 years unless in&#xD;
             complete remission since at least 3 years&#xD;
&#xD;
          -  Dependency on red blood cell and/or platelet transfusions&#xD;
&#xD;
          -  HBsAg positivity&#xD;
&#xD;
          -  Evidence of central nervous system involvement&#xD;
&#xD;
          -  A history of uncontrolled seizures, central nervous system disorders or psychiatric&#xD;
             disability judged by the investigator to be clinically significant and adversely&#xD;
             affecting compliance to study drugs&#xD;
&#xD;
          -  Severe peripheral polyneuropathy&#xD;
&#xD;
          -  Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic&#xD;
             coronary artery disease and cardiac arrhythmias not well controlled with medication)&#xD;
             or myocardial infarction within the last 6 months and/or long QT-syndrome&#xD;
&#xD;
          -  HIV seropositivity&#xD;
&#xD;
          -  Presence of active opportunistic infections&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus&#xD;
&#xD;
          -  Pre-existing thromboembolic conditions at study entry&#xD;
&#xD;
          -  Known hypersensitivity to thalidomide or lenalidomide or macrolide antibiotics&#xD;
&#xD;
          -  Presence of any contraindication reported on the Summary of Product Characteristics&#xD;
             (SmPC) of Clarithromycin&#xD;
&#xD;
          -  Hypersensitivity to any active principle and/or any excipient according to the&#xD;
             contraindications reported in the SmPC of clarithromycin and in the Investigator's&#xD;
             Brochure (IB) of lenalidomide&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emanuele Zucca, Prof</last_name>
    <role>Study Director</role>
    <affiliation>International Extranodal Lymphoma Study Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <state>FI</state>
        <zip>50141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Centro di Riferimento Oncologico di Aviano</name>
      <address>
        <city>Aviano</city>
        <state>PN</state>
        <zip>33061</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Ospedali Riuniti</name>
      <address>
        <city>Ancona</city>
        <zip>60100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS AOU San Martino - IST Genova</name>
      <address>
        <city>Genova</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Papardo</name>
      <address>
        <city>Messina</city>
        <zip>98158</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS - Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera di Padova</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS - Policlinico San Matteo</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Civile Spirito Santo Pescara</name>
      <address>
        <city>Pescara</city>
        <zip>65124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Guglielmo da Saliceto</name>
      <address>
        <city>Piacenza</city>
        <zip>29121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Arcispedale Santa maria Nuova IRCCS</name>
      <address>
        <city>Reggio Emilia</city>
        <zip>42123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale di Circolo e Fondazione Macchi di Varese</name>
      <address>
        <city>Varese</city>
        <zip>21100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOUI Verona - Ospedale Borgo Roma</name>
      <address>
        <city>Verona</city>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Sanitaria ULSS 6 - Ospedale S.Bortolo</name>
      <address>
        <city>Vicenza</city>
        <zip>36100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Enfermedades Hematológicas y Oncológicas</name>
      <address>
        <city>Barcelona</city>
        <state>Barcellona</state>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Català D'Oncologia Hospital Duran I Reynals</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Madrid</city>
        <zip>28033</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Italy</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>November 4, 2022</last_update_submitted>
  <last_update_submitted_qc>November 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 7, 2022</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clarithromycin</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03031483
org study id: IELSG40
nct id: NCT03031483
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with lymphoid tissue lymphoma mucosa-associated (MALT) for which the standard
      treatments with radiotherapy, chemotherapy and / or immunotherapy show lack of efficacy
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: Tumor response assessment
time frame: During the active treatment period after the 3rd cycles of both drugs administration
description: The primary outcome measure is tumour response assessed according to the Revised Response Criteria for Malignant Lymphoma, either clinically (including appropriate imaging procedures) or endoscopically and histologically (in patients affected by gastric lymphoma, according to the GELA scoring system).
measure: Adverse Events assessments
time frame: During the active treatment period
description: Treatment-emergent adverse events (AEs) incidence, severity and relationship to study treatment.
Time from first IMP administration to assessment of disease progression or death due to any cause, whichever occurs earlier.
arm group label: Experimental: clarithromycin and lenalidomide
arm group type: Experimental
description: CLARITHROMYCIN: daily orally administration in cycles of 28 days; 500mg film-coated tablets LENALIDOMIDE: every cycle of treatment lasts 28 days; daily orally administration is of 21 consecutive days with a week of rest. 20mg capsule hard. The maximum treatment duration is 12 months.
intervention type: Drug
intervention name: clarithromycin and lenalidomide
description: Each treatment course will consist of:
Oral Lenalidomide (Revlimid) once daily for 21 days at a dose 20 mg; in case of drug-related adverse events the dose can be reduced to 15 and 10 mg/day; Oral Clarithromycin 500 mg twice daily for 28 days. Courses will be repeated every 28 days. After the first 3 courses patients with stable disease or better response will be given another three courses. Patients with complete remission or disease progression after 6 courses will be taken off study, while patients with partial response or stable disease will receive 3 further courses of treatment. Again, patients with complete response or disease progression will stop therapy, while patients with partial response/stable disease will receive 3 further courses up to a maximum of 12 courses in total.
arm group label: Experimental: clarithromycin and lenalidomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Emanuele Zucca, Prof
role: Study Director
affiliation: International Extranodal Lymphoma Study Group
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country: Austria
country: Italy
country: Spain
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Clarithromycin
mesh term: Lenalidomide