<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/NCT02227433</url>
  </required_header>
  <id_info>
    <org_study_id>FIL_BVHD01</org_study_id>
    <nct_id>NCT02227433</nct_id>
  </id_info>
  <brief_title>Brentuximab Vedotin in the Elderly Hodgkin Lymphoma Patients at First Relapse or With Primary Refractory Disease.</brief_title>
  <acronym>FIL_BVHD01</acronym>
  <official_title>A Phase II Study of Brentuximab Vedotin (BV) in the Treatment of Elderly Hodgkin Lymphoma (HL) Patients at First Relapse or With Primary Refractory Disease.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione Italiana Linfomi - ETS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione Italiana Linfomi - ETS</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-arm, open-label, multicenter, clinical trial to evaluate the efficacy and&#xD;
      safety of BV as a single agent in elderly patients at first relapse or with primary&#xD;
      refractory HL.&#xD;
&#xD;
      BV will be administered as a single IV infusion on Day 1 of each 21-day cycle. Measures of&#xD;
      anti-cancer activity will be assessed using the revised response criteria for malignant&#xD;
      lymphoma (Cheson et al. 2007).&#xD;
&#xD;
      Computed tomography (CT) scans (chest, neck, abdomen, and pelvis) will be performed at&#xD;
      baseline and Cycles 4, 8, 12, and 16 and positron emission tomography (PET) scans will be&#xD;
      done at baseline and Cycles 4, 8, 12 and 16. Patients will have an End of Treatment (EOT)&#xD;
      assessment 30 ± 7 days after receiving their final dose of study drug. Long-term follow-up&#xD;
      assessments (including survival and disease status information) will be performed every 12&#xD;
      weeks until either patient death or study closure, whichever occurs first. Patients who&#xD;
      discontinue study treatment with stable disease or better will have CT scans done every 12&#xD;
      weeks until disease progression.&#xD;
&#xD;
      Study Objectives&#xD;
&#xD;
      Primary:&#xD;
&#xD;
      • To determine the antitumor efficacy of single-agent brentuximab vedotin (BV) (1.8 mg/kg&#xD;
      administered intravenously every 3 weeks) as measured by the overall objective response rate&#xD;
      in elderly patients at first relapse or with primary refractory Hodgkin lymphoma (HL).&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
        -  To assess duration of tumor control, including duration of response and progression-free&#xD;
           survival&#xD;
&#xD;
        -  To assess survival&#xD;
&#xD;
        -  To assess the safety and tolerability of BV&#xD;
&#xD;
      Additional:&#xD;
&#xD;
      • To assess disease-related symptoms Study Population Eligible patients are those with first&#xD;
      relapsed or primary refractory elderly HL. Patients must also have histologically-confirmed&#xD;
      CD30-positive disease, fluorodeoxyglucose (FDG)-avid and measurable disease of at least 1.5&#xD;
      cm, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate&#xD;
      hematologic, kidney, and liver function. Eligible patients must not previously have been&#xD;
      treated with BV, patients must not have congestive heart failure, known cerebral/meningeal&#xD;
      disease, or any active viral, bacterial, or fungal infection requiring treatment with&#xD;
      antimicrobial therapy within 2 weeks prior to first study dose.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 4, 2013</start_date>
  <completion_date type="Actual">April 2020</completion_date>
  <primary_completion_date type="Actual">April 3, 2018</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>Antitumor Efficacy</measure>
    <time_frame>two years</time_frame>
    <description>• The antitumor efficacy of single-agent brentuximab vedotin (BV) (1.8 mg/kg administered intravenously every 3 weeks) as measured by the overall objective response rate in elderly patients at first relapse or with primary refractory Hodgkin lymphoma (HL).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival, safety and tolerability</measure>
    <time_frame>two years</time_frame>
    <description>• The duration of tumor control, including duration of response and progression-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>Two years</time_frame>
    <description>• The survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of Brentuximab Vedotin</measure>
    <time_frame>Two years</time_frame>
    <description>• The safety and tolerability of BV</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease related symptoms</measure>
    <time_frame>Two years</time_frame>
    <description>Additional:&#xD;
• The disease-related symptoms</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>brentuximab vedotin (BV)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin</intervention_name>
    <arm_group_label>brentuximab vedotin (BV)</arm_group_label>
    <other_name>SGN</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed CD30-positive disease&#xD;
&#xD;
          2. Elderly patients at first relapse or with primary refractory HL (i.e. patients who&#xD;
             have previously received only 1 line of treatment.&#xD;
&#xD;
          3. Patients must have completed any prior treatment with radiation, chemotherapy,&#xD;
             biologics, immunotherapy and/or other investigational agents greater than 5 half-lives&#xD;
             of the last dose of that prior treatment prior to the first dose of BV and must have&#xD;
             fully recovered from the acute toxic effects prior to entering this study.&#xD;
&#xD;
          4. Age greater than or equal to 60 years.&#xD;
&#xD;
          5. Fluorodeoxyglucose (FDG)-avid and measurable disease of at least 1.5 cm as documented&#xD;
             by both PET and spiral CT.&#xD;
&#xD;
          6. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          7. The following required baseline laboratory data: absolute neutrophil count (ANC)&#xD;
             ≥1500/µL, unless known marrow involvement due to disease, platelets ≥75,000/µL, unless&#xD;
             known marrow involvement due to disease, bilirubin ≤1.5X upper limit of normal (ULN)&#xD;
             or ≤3X ULN for patients with Gilbert's disease, serum creatinine ≤1.5X ULN, alanine&#xD;
             aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5X ULN.&#xD;
&#xD;
          8. Females of childbearing potential must have a negative serum or urine β-hCG pregnancy&#xD;
             test result prior to the first dose of brentuximab vedotin. Females of&#xD;
             non-childbearing potential are those who are postmenopausal greater than 1 year or who&#xD;
             have had a bilateral tubal ligation or hysterectomy.&#xD;
&#xD;
          9. Females of childbearing potential must agree to use two effective contraceptive&#xD;
             methods during the study and for 6 months following the last dose of study drug or&#xD;
             agree to completely abstain from heterosexual intercourse.&#xD;
&#xD;
         10. Males, even if surgically sterilized, (i.e., status post vasectomy) must agree to&#xD;
             practice effective barrier contraception during the entire study period and through 6&#xD;
             months after the last dose of study drug or agree to completely abstain from&#xD;
             heterosexual intercourse.&#xD;
&#xD;
         11. Patients must provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with BV&#xD;
&#xD;
          2. Peripheral neuropathy &gt; grade 1.&#xD;
&#xD;
          3. Known history of any of the following cardiovascular conditions:&#xD;
&#xD;
               1. Myocardial infarction within 2 years of study entry.&#xD;
&#xD;
               2. Congestive heart failure, Class III or IV, by the NYHA criteria.&#xD;
&#xD;
               3. Evidence of current uncontrolled cardiac arrhythmias, angina, or&#xD;
                  electrocardiographic evidence of acute ischemia or active conduction system&#xD;
                  abnormalities.&#xD;
&#xD;
               4. Recent evidence (within 6 months of study entry) of a left ventricular ejection&#xD;
                  fraction &lt;50%4) History of another primary malignancy for within 3 years of study&#xD;
                  entry. (The following are exempt from the 3-year limit: nonmelanoma skin cancer,&#xD;
                  curatively treated localized prostate cancer, and cervical carcinoma in situ on&#xD;
                  biopsy or a squamous intraepithelial lesion on PAP smear.)&#xD;
&#xD;
        5) Known cerebral/meningeal disease. 6) Signs or symptoms of progressive multifocal&#xD;
        leukoencephalopathy (PML). 7) Any active systemic viral, bacterial, or fungal infection&#xD;
        requiring treatment with antimicrobial therapy within 2 weeks prior to the first dose of&#xD;
        BV. 8) Current therapy with other systemic anti-neoplastic or investigational agents.&#xD;
&#xD;
        9) Therapy with corticosteroids at greater than or equal to 20 mg/day prednisone equivalent&#xD;
        within 1 week prior to the first dose of BV. 10) Women who are pregnant or lactating and&#xD;
        breastfeeding. 11) Patients with a known hypersensitivity to recombinant proteins, murine&#xD;
        proteins, or any excipient contained in the drug formulation of brentuximab vedotin. 12)&#xD;
        Known human immunodeficiency virus (HIV) positive. 13) Known hepatitis B surface antigen&#xD;
        positive, or known or suspected active hepatitis C infection.&#xD;
&#xD;
        14) Patients with dementia or an altered mental state that would preclude the understanding&#xD;
        and rendering of informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vittorio Stefoni</last_name>
    <role>Principal Investigator</role>
    <affiliation>AO S. Orsola Malpighi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ASST Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irccs Centro Di Riferimento Oncologico Di Aviano (Pn)</name>
      <address>
        <city>Aviano</city>
        <state>Italia</state>
        <zip>33081</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico S.Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irccs Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale Di Napoli</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Umberto I - Università &quot;La Sapienza&quot; - Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione</name>
      <address>
        <city>Rome</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>December 21, 2020</last_update_submitted>
  <last_update_submitted_qc>December 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hodgkin Lymphoma, Elderly Patients, brentuximab vedotin (BV)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brentuximab Vedotin</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/NCT02227433
org study id: FIL_BVHD01
nct id: NCT02227433
lead sponsor: 
has dmc: No
This is a single-arm, open-label, multicenter, clinical trial to evaluate the efficacy and
      safety of BV as a single agent in elderly patients at first relapse or with primary
      refractory HL.

      BV will be administered as a single IV infusion on Day 1 of each 21-day cycle. Measures of
      anti-cancer activity will be assessed using the revised response criteria for malignant
      lymphoma (Cheson et al. 2007).

      Computed tomography (CT) scans (chest, neck, abdomen, and pelvis) will be performed at
      baseline and Cycles 4, 8, 12, and 16 and positron emission tomography (PET) scans will be
      done at baseline and Cycles 4, 8, 12 and 16. Patients will have an End of Treatment (EOT)
      assessment 30 ± 7 days after receiving their final dose of study drug. Long-term follow-up
      assessments (including survival and disease status information) will be performed every 12
      weeks until either patient death or study closure, whichever occurs first. Patients who
      discontinue study treatment with stable disease or better will have CT scans done every 12
      weeks until disease progression.

      Study Objectives

      Primary:

      • To determine the antitumor efficacy of single-agent brentuximab vedotin (BV) (1.8 mg/kg
      administered intravenously every 3 weeks) as measured by the overall objective response rate
      in elderly patients at first relapse or with primary refractory Hodgkin lymphoma (HL).

      Secondary:

        -  To assess duration of tumor control, including duration of response and progression-free
           survival

        -  To assess survival

        -  To assess the safety and tolerability of BV

      Additional:

      • To assess disease-related symptoms Study Population Eligible patients are those with first
      relapsed or primary refractory elderly HL. Patients must also have histologically-confirmed
      CD30-positive disease, fluorodeoxyglucose (FDG)-avid and measurable disease of at least 1.5
      cm, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate
      hematologic, kidney, and liver function. Eligible patients must not previously have been
      treated with BV, patients must not have congestive heart failure, known cerebral/meningeal
      disease, or any active viral, bacterial, or fungal infection requiring treatment with
      antimicrobial therapy within 2 weeks prior to first study dose.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Antitumor Efficacy
time frame: two years
description: • The antitumor efficacy of single-agent brentuximab vedotin (BV) (1.8 mg/kg administered intravenously every 3 weeks) as measured by the overall objective response rate in elderly patients at first relapse or with primary refractory Hodgkin lymphoma (HL).
measure: Survival, safety and tolerability
time frame: two years
description: • The duration of tumor control, including duration of response and progression-free survival
measure: Survival
time frame: Two years
description: • The survival
measure: Safety and tolerability of Brentuximab Vedotin
time frame: Two years
description: • The safety and tolerability of BV
measure: Disease related symptoms
time frame: Two years
description: Additional:
• The disease-related symptoms
arm group label: brentuximab vedotin (BV)
arm group type: Experimental
intervention type: Drug
intervention name: Brentuximab Vedotin
arm group label: brentuximab vedotin (BV)
other name: SGN
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Vittorio Stefoni
role: Principal Investigator
affiliation: AO S. Orsola Malpighi
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Brentuximab Vedotin