<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/NCT02244021</url>
  </required_header>
  <id_info>
    <org_study_id>FIL_BRidge</org_study_id>
    <nct_id>NCT02244021</nct_id>
  </id_info>
  <brief_title>BRENTUXIMAB VEDOTIN as Pre-ASCT Induction Therapy in R/R HL Patients Non Responding to IGEV</brief_title>
  <official_title>A Pilot Phase II Study With BRENTUXIMAB VEDOTIN as Pre-ASCT Induction Therapy in Relapsed/Refractory Hodgkin's Lymphoma Patients Non Responding to IGEV Salvage Treatment</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>
      A pilot phase II study with brentuximab vedotin as pre-ASCT induction therapy in&#xD;
      relapsed/refractory Hodgkin's lymphoma patients non-responding to IGEV salvage treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Brentuximab vedotin emerged as active single-agent in the treatment of relapsed or refractory&#xD;
      HL.&#xD;
&#xD;
      Some patients don't reach a complete response after salvage treatment with IGEV (ifosfamide,&#xD;
      gemcitabine, vinorelbine) and remain PET positive so the idea is to treat this subset of&#xD;
      patients with brentuximab vedotin with the aim of achieving a complete remission before&#xD;
      transplant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">October 2017</completion_date>
  <primary_completion_date type="Actual">July 2016</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>Complete response (CR rate)</measure>
    <time_frame>1 year and half from the beginning of the study</time_frame>
    <description>Complete response will be defined according to recently updated international criteria (Cheson 2007), assuming that a negative PET is defined by DEAUVILLE scores 1 and 2.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>2 years and half from the beginning of the study</time_frame>
    <description>Additional study endpoint is final response to Brentuximab vedotin followed by autologous stem cell transplantation (ASCT), in terms of progression free survival (PFS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurotoxicity rate</measure>
    <time_frame>1 year half from the beginning of the study</time_frame>
    <description>Neurotoxicity of any grade defined as National Cancer Institute Common Terminology Criteria for Adverse Events , version 4.03 (NCI CTCEA, 2010)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of remission (DR)</measure>
    <time_frame>2 years and half from the beginning of the study</time_frame>
    <description>Additional study endpoint is final response to Brentuximab vedotin followed by autologous stem cell transplantation (ASCT), in terms of duration of remission (DR).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Relapsed/Refractory Hodgkin's Lymphoma</condition>
  <arm_group>
    <arm_group_label>BRENTUXIMAB VEDOTIN</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 arm for all patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BRENTUXIMAB VEDOTIN</intervention_name>
    <description>Patients with FDG-PET positive after IGEV will be treated with brentuximab vedotin as followed: 1.8 mg/kg every 3 weeks as a 30-minute outpatient IV infusion for a total of 4 cycles of treatment&#xD;
Growth factors may be used at the discretion of investigators but are not routinely advised.&#xD;
Patients with FDG-PET negative after brentuximab vedotin treatment will be addressed to high dose chemotherapy followed by ASCT.</description>
    <arm_group_label>BRENTUXIMAB VEDOTIN</arm_group_label>
    <other_name>SGN-35</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Classical Hodgkin Lymphoma according to the WHO classification&#xD;
&#xD;
          2. Histologically confirmed CD30+ HL at diagnosis&#xD;
&#xD;
          3. Patients at the first line salvage therapy&#xD;
&#xD;
          4. FDG-PET positivity after two cycles of IGEV treatment&#xD;
&#xD;
          5. PBPCs should have been collected after the first or the second IGEV cycle&#xD;
&#xD;
          6. Age≥ 18 years&#xD;
&#xD;
          7. ECOG PS of 0-2&#xD;
&#xD;
          8. Life expectancy &gt; 6 months.&#xD;
&#xD;
          9. Written informed consent&#xD;
&#xD;
         10. Patients available for periodic blood sampling, study-related assessments and&#xD;
             management of toxicity&#xD;
&#xD;
         11. Females of childbearing potential must have a negative β-HCG pregnancy test result&#xD;
             (pregnancy test should be performed at screening an on day 1 of cycle 1 prior to&#xD;
             brentuximab vedotin treatment).&#xD;
&#xD;
         12. Female patient is either post-menopausal for at least 1 year before the screening&#xD;
             visit or surgically sterile or if of childbearing potential, agree to practice 2&#xD;
             effective methods of contraception, at the same time, from the time of signing the&#xD;
             informed consent through 6 months after the last dose of study drug, or agrees to&#xD;
             completely abstain from heterosexual intercourse.&#xD;
&#xD;
         13. Male patients, even if surgically sterilized, (i.e., status post vasectomy) 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 agrees to completely abstain from&#xD;
             heterosexual intercourse.&#xD;
&#xD;
         14. Required baseline laboratory data: Absolute neutrophil count ≥ 1500/µl, Platelet count&#xD;
             ≥ 75.000/ µl, Haemoglobin must be ≥ 8 g/dL, Serum bilirubin ≤ 1.5 times ULN, Serum&#xD;
             creatinine &lt; 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance&#xD;
             &gt; 40 mL/minute, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤&#xD;
             2.5 times ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Peripheral neuropathy &gt; Grade 1&#xD;
&#xD;
          2. Histologic diagnosis different from Hodgkin Lymphoma&#xD;
&#xD;
          3. First line treatment with BEACOPP&#xD;
&#xD;
          4. Compressive symptoms caused by the presence of Lymphoma&#xD;
&#xD;
          5. Patients treated previously with any anti-CD30 antibody.&#xD;
&#xD;
          6. Known hypersensitivity to any recombinant proteins, murine proteins, or excipients&#xD;
             contained in the brentuximab vedotin formulation.&#xD;
&#xD;
          7. Known human immunodeficiency virus (HIV) positive&#xD;
&#xD;
          8. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C&#xD;
             infection&#xD;
&#xD;
          9. Diagnosed or treated for another malignancy within 3 years before the first dose or&#xD;
             previously diagnosed with another malignancy and have evidence of residual disease.&#xD;
             Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not&#xD;
             excluded if they have undergone complete resection.&#xD;
&#xD;
         10. Patients with known history of any of the following cardiovascular&#xD;
             conditions:Myocardial infarction within 2 years of randomization, New York Heart&#xD;
             Association (NYHA) Class III or IV heart failure, Evidence of current uncontrolled&#xD;
             cardiovascular conditions, including cardiac arrhythmias, congestive heart failure&#xD;
             (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction&#xD;
             system abnormalities, Recent evidence (within 6 months before first dose of study&#xD;
             drug) of a left-ventricular ejection fraction &lt;50%&#xD;
&#xD;
         11. Patients with known active viral, bacterial, or fungal infection requiring treatment&#xD;
             with antimicrobial therapy within 2 weeks prior to the first dose of brentuximab&#xD;
             vedotin.&#xD;
&#xD;
         12. Patients with known active Grade 3 or higher viral, bacterial, or fungal infection&#xD;
             within 2 weeks prior to the first dose of brentuximab vedotin.&#xD;
&#xD;
         13. Patients with known cerebral/meningeal disease (HL or any other etiology), including&#xD;
             signs or symptoms of Progressive Multifocal Leukoencephalopathy&#xD;
&#xD;
         14. Any serious medical or psychiatric illness that could, in the investigator's opinion,&#xD;
             potentially interfere with the completion of treatment according to protocol.&#xD;
&#xD;
         15. Symptomatic neurologic disease compromising normal activities of daily living or&#xD;
             requiring medications.&#xD;
&#xD;
         16. Patients who are pregnant, or lactating and breastfeeding.&#xD;
&#xD;
         17. Patients that have not completed any prior treatment chemotherapy and/or other&#xD;
             investigational agents within at least 5 half-lives of last dose of that prior&#xD;
             treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Angelo Michele Carella, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hematology Division, IRCCS AOU San Martino, Genova, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Istituto di Ematologia &quot;L. &amp; A. Seragnoli&quot; , Policlinico S. Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia, IRCCS AOU San Martino-IST</name>
      <address>
        <city>Genova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia Ospedale Vito Fazzi</name>
      <address>
        <city>Lecce</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia e Unità BMT IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università degli Studi di Modena e Reggio Emilia, D.A.I di Medicina diagnostica clinica e sanità pubblica, AOU Policlinico</name>
      <address>
        <city>Modena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dipartimento di Oncologia Medica ed Ematologia, Istituto Humanitas</name>
      <address>
        <city>Rozzano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC Ematologia - Azienda Ospedaliera AO Città della Salute e della Scienza</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2014</study_first_posted>
  <last_update_submitted>February 8, 2018</last_update_submitted>
  <last_update_submitted_qc>February 8, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HD</keyword>
  <keyword>Hodgkin's Lymphoma</keyword>
  <keyword>RELAPSED-REFRACTORY</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/NCT02244021
org study id: FIL_BRidge
nct id: NCT02244021
lead sponsor: 
has dmc: No
A pilot phase II study with brentuximab vedotin as pre-ASCT induction therapy in
      relapsed/refractory Hodgkin's lymphoma patients non-responding to IGEV salvage treatment.
Brentuximab vedotin emerged as active single-agent in the treatment of relapsed or refractory
      HL.

      Some patients don't reach a complete response after salvage treatment with IGEV (ifosfamide,
      gemcitabine, vinorelbine) and remain PET positive so the idea is to treat this subset of
      patients with brentuximab vedotin with the aim of achieving a complete remission before
      transplant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete response (CR rate)
time frame: 1 year and half from the beginning of the study
description: Complete response will be defined according to recently updated international criteria (Cheson 2007), assuming that a negative PET is defined by DEAUVILLE scores 1 and 2.
measure: PFS
time frame: 2 years and half from the beginning of the study
description: Additional study endpoint is final response to Brentuximab vedotin followed by autologous stem cell transplantation (ASCT), in terms of progression free survival (PFS).
measure: Neurotoxicity rate
time frame: 1 year half from the beginning of the study
description: Neurotoxicity of any grade defined as National Cancer Institute Common Terminology Criteria for Adverse Events , version 4.03 (NCI CTCEA, 2010)
measure: Duration of remission (DR)
time frame: 2 years and half from the beginning of the study
description: Additional study endpoint is final response to Brentuximab vedotin followed by autologous stem cell transplantation (ASCT), in terms of duration of remission (DR).
arm group label: BRENTUXIMAB VEDOTIN
arm group type: Experimental
description: 1 arm for all patients
intervention type: Drug
intervention name: BRENTUXIMAB VEDOTIN
description: Patients with FDG-PET positive after IGEV will be treated with brentuximab vedotin as followed: 1.8 mg/kg every 3 weeks as a 30-minute outpatient IV infusion for a total of 4 cycles of treatment
Growth factors may be used at the discretion of investigators but are not routinely advised.
Patients with FDG-PET negative after brentuximab vedotin treatment will be addressed to high dose chemotherapy followed by ASCT.
arm group label: BRENTUXIMAB VEDOTIN
other name: SGN-35
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Angelo Michele Carella, Prof.
role: Principal Investigator
affiliation: Hematology Division, IRCCS AOU San Martino, Genova, Italy
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Brentuximab Vedotin