<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/NCT02247869</url>
  </required_header>
  <id_info>
    <org_study_id>FIL - DDABVD</org_study_id>
    <nct_id>NCT02247869</nct_id>
  </id_info>
  <brief_title>Dose-dense ABVD First Line Therapy in Early Stage Unfavorable Hodgkin's Lymphoma</brief_title>
  <official_title>Dose-dense ABVD as First Line Therapy in Early Stage Unfavorable Hodgkin's Lymphoma: a Phase II, Prospective, Multi-center Study</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>
      Prospective, multicenter, Phase II trial designed to assess whether intensification of ABVD&#xD;
      (dd-ABVD) is feasible and can improve the outcome of patients with early stage Hodgkin&#xD;
      Lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dose-density has been shown to be an important factor for complete remission rate and&#xD;
      longterm survival in lymphomas.&#xD;
&#xD;
      The aims of this study were to find out whether intensification of ABVD (dd-ABVD) is feasible&#xD;
      and can improve the outcome of patients with early stage Hodgkin Lymphoma. In view of&#xD;
      emerging data on the role of early PET in defining prognosis in Hodgkin Lymphoma patients,&#xD;
      the percentage of FDG-PET (fluorodeoxyglucose positron emission tomography) negativity after&#xD;
      two cycle was chosen as the parameter to evaluate dd-ABVD activity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2012</start_date>
  <completion_date type="Actual">April 29, 2017</completion_date>
  <primary_completion_date type="Actual">June 2015</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>Feasibility</measure>
    <time_frame>After 4 dd-ABVD cycles (12 weeks after starting treatment)</time_frame>
    <description>Proportion of patient with a dose intensity reduction (lower than 85% of planned dose)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Activity</measure>
    <time_frame>After 2 dd-ABVD cycles (6 week after starting treatment)</time_frame>
    <description>Percentage of FDG PET negativity after 2 dd-ABVD cycles will be considered as primary endpoints.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall accuracy of each interim PET interpretation criteria after a minimum follow-up of three years</measure>
    <time_frame>After 3 years of follow-up</time_frame>
    <description>Concordance between pet results and patients prognosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>2 years from the activation of therapy in the last patient enrolled onto the study.</time_frame>
    <description>Progression free survival estimate (prognosis outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>2 years from the activation of therapy in the last patient enrolled onto the study.</time_frame>
    <description>Overall survival estimate (prognosis outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity</measure>
    <time_frame>2 years from the activation of therapy in the last patient enrolled onto the study.</time_frame>
    <description>Proportion of early and late toxicities (G3/4 acute toxicities, secondary malignancies, cardiovascular and pulmonary events, infertility)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive Value of each interim PET interpretation criteria after a minimum follow-up of three years</measure>
    <time_frame>After 3 years of follow-up</time_frame>
    <description>Concordance between pet results and patients prognosis</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>dose dense ABVD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 arm for all patients (dose dense ABVD on day 1 and 8 every 21 days)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dose dense ABVD</intervention_name>
    <description>dose dense ABVD will be administered intravenously on day 1 and 8 every 21 days Chemotherapy regimen&#xD;
Doxorubicin 25 mg/m2 i.v. day 1 and 8&#xD;
Bleomycin 10 mg/m2 i.v. day 1 and 8&#xD;
Vinblastine 6 mg/m2 i.v. day 1 and 8&#xD;
Dacarbazine 375 mg/m2 i.v. day 1 and 8&#xD;
Granulocyte colony-stimulating factor (G-CSF): days 9 to 14</description>
    <arm_group_label>dose dense ABVD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-70 years&#xD;
&#xD;
          -  Histologically confirmed Hodgkin Lymphoma stage I, II unfavorable according to EORTC&#xD;
             (European Organisation for Research and Treatment of Cancer) criteria, with exclusion&#xD;
             of stage II B bulky.&#xD;
&#xD;
          -  Previously untreated&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Oncology Group) performance status 0 - 2&#xD;
&#xD;
          -  Staging with FDG-PET (fluorodeoxyglucose positron emission tomography)&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Adequate liver and renal function (total serum bilirubin &lt; 2.5 x ULN, AST/SGOT and/or&#xD;
             ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase&#xD;
             elevation is due to disease involvement, serum creatinine &lt; 2.5 x ULN)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant cardiac, pulmonary, neurologic, psychiatric or metabolic severe disease.&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus (with fasting glucose levels above 200mg/dl)&#xD;
&#xD;
          -  Other prior malignancies except for adequately treated basal cell carcinoma, squamous&#xD;
             cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the&#xD;
             breast or other cancer from which the patient has been disease-free for ≥ 3 years&#xD;
&#xD;
          -  Patients with a known history of HIV seropositivity&#xD;
&#xD;
          -  Active HCV infection (PCR + ; AST&gt; 1.5-2x UN)&#xD;
&#xD;
          -  Woman who is pregnant or breast feeding. Fertile patients not willing to use effective&#xD;
             contraception during the study and 3 months after the end of treatment. Women of&#xD;
             childbearing potential (WOCBP) are defined as sexually mature women who have not&#xD;
             undergone a hysterectomy or who have not been naturally postmenopausal for at least 12&#xD;
             consecutive months.&#xD;
&#xD;
          -  Negative pregnancy test at baseline is required (serum β HCG).&#xD;
&#xD;
          -  Male patient whose sexual partner(s) are WOCBP who are not willing to use a effective&#xD;
             contraception during the study and 3 months after the end of treatment&#xD;
&#xD;
          -  Nodular lymphocyte prevalence histological subtype&#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>Armando Santoro, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Humanitas Cancer Center - Department of Medical Oncology and Haematology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UO Ematologia Casa Sollievo della Sofferenza</name>
      <address>
        <city>San Giovanni Rotondo</city>
        <state>Foggia</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dipartimento di Oncologia Medica ed Ematologia Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncologia HSR Giglio</name>
      <address>
        <city>Cefalù</city>
        <state>Palermo</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncologia Medica A Centro di Riferimento Oncologico</name>
      <address>
        <city>Aviano</city>
        <state>Pordenone</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U.O. Oncoematologia Ospedale &quot;Andrea Tortora&quot;</name>
      <address>
        <city>Pagani</city>
        <state>Salerno</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Ematologia Ospedale San Donato</name>
      <address>
        <city>Arezzo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Ematologia con trapianto AOU Policlinico Consorziale</name>
      <address>
        <city>Bari</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SOS Ematologia Divisione Medicina Interna Ospedale degli Infermi</name>
      <address>
        <city>Biella</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia e CTMO Ospedale Businco</name>
      <address>
        <city>Cagliari</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UOC Oncoematologia Garibaldi Nesima</name>
      <address>
        <city>Catania</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UOC Ematologia Azienda Ospedaliera Cosenza</name>
      <address>
        <city>Cosenza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unità Funzionale di Ematologia AOU Careggi</name>
      <address>
        <city>Firenze</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia- AOU San Martino IRCCS - IST</name>
      <address>
        <city>Genova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC Medicina Trasfusionale ed Ematologia SS Ematologia ASLTO4</name>
      <address>
        <city>Ivrea</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Ematologia PO Vito Fazzi</name>
      <address>
        <city>Lecce</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRST Meldola</name>
      <address>
        <city>Meldola</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC Ematologia AO Riuniti Papardo Piemonte</name>
      <address>
        <city>Messina</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Oncoematologia AO San Carlo Borromeo Unità Semplice di Trapianto Midollo</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Oncoematologico Policlinico</name>
      <address>
        <city>Modena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unità Complessa di Ematologia AO di Rilievo Nazionale A. Cardarelli</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCDU Ematologia Università Piemonte Orientale</name>
      <address>
        <city>Novara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncoematologia e TMO Dopartimento Oncologia La Maddalena</name>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Complessa di Ematologia Ospedale di Parma</name>
      <address>
        <city>Parma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Ematologica Fondazione IRCCS Policlinico San Matteo</name>
      <address>
        <city>Pavia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia Ospedale Santo Spirito</name>
      <address>
        <city>Pescara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Ematologia Ospedale Santa Maria delle Croci</name>
      <address>
        <city>Ravenna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC Ematologia Azienda Ospedaliera Arcispedale Santa Maria Nuova</name>
      <address>
        <city>Reggio Emilia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Oncoematologia AUSL Rimini Ospedale Infermi</name>
      <address>
        <city>Rimini</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia e Trapianto Istituto Regina Elena IFO</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia Ospedale Sant'Andrea</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia Università La Sapienza</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ematologia e Trapianti AO San Giovanni di Dio e Ruggi D'Aragona</name>
      <address>
        <city>Salerno</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Università Senese Clinica Ematologica Policlinico Le Scotte</name>
      <address>
        <city>Siena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncoematologia Università Perugia sede Terni</name>
      <address>
        <city>Terni</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC Ematologia AO Città della Salute e della Scienza</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Ematologica AO S. Maria della Misericordia</name>
      <address>
        <city>Udine</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UOC Ematologia Ospedale di Circolo</name>
      <address>
        <city>Varese</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>March 7, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 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>HL</keyword>
  <keyword>Hodgkin Lymphoma</keyword>
  <keyword>First line therapy</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>
  <!-- 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/NCT02247869
org study id: FIL - DDABVD
nct id: NCT02247869
lead sponsor: 
has dmc: No
Prospective, multicenter, Phase II trial designed to assess whether intensification of ABVD
      (dd-ABVD) is feasible and can improve the outcome of patients with early stage Hodgkin
      Lymphoma.
Dose-density has been shown to be an important factor for complete remission rate and
      longterm survival in lymphomas.

      The aims of this study were to find out whether intensification of ABVD (dd-ABVD) is feasible
      and can improve the outcome of patients with early stage Hodgkin Lymphoma. In view of
      emerging data on the role of early PET in defining prognosis in Hodgkin Lymphoma patients,
      the percentage of FDG-PET (fluorodeoxyglucose positron emission tomography) negativity after
      two cycle was chosen as the parameter to evaluate dd-ABVD activity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility
time frame: After 4 dd-ABVD cycles (12 weeks after starting treatment)
description: Proportion of patient with a dose intensity reduction (lower than 85% of planned dose)
measure: Activity
time frame: After 2 dd-ABVD cycles (6 week after starting treatment)
description: Percentage of FDG PET negativity after 2 dd-ABVD cycles will be considered as primary endpoints.
measure: Overall accuracy of each interim PET interpretation criteria after a minimum follow-up of three years
time frame: After 3 years of follow-up
description: Concordance between pet results and patients prognosis
measure: PFS
time frame: 2 years from the activation of therapy in the last patient enrolled onto the study.
description: Progression free survival estimate (prognosis outcome)
measure: OS
time frame: 2 years from the activation of therapy in the last patient enrolled onto the study.
description: Overall survival estimate (prognosis outcome)
measure: Toxicity
time frame: 2 years from the activation of therapy in the last patient enrolled onto the study.
description: Proportion of early and late toxicities (G3/4 acute toxicities, secondary malignancies, cardiovascular and pulmonary events, infertility)
measure: Predictive Value of each interim PET interpretation criteria after a minimum follow-up of three years
time frame: After 3 years of follow-up
description: Concordance between pet results and patients prognosis
arm group label: dose dense ABVD
arm group type: Experimental
description: 1 arm for all patients (dose dense ABVD on day 1 and 8 every 21 days)
intervention type: Drug
intervention name: dose dense ABVD
description: dose dense ABVD will be administered intravenously on day 1 and 8 every 21 days Chemotherapy regimen
Doxorubicin 25 mg/m2 i.v. day 1 and 8
Bleomycin 10 mg/m2 i.v. day 1 and 8
Vinblastine 6 mg/m2 i.v. day 1 and 8
Dacarbazine 375 mg/m2 i.v. day 1 and 8
Granulocyte colony-stimulating factor (G-CSF): days 9 to 14
arm group label: dose dense ABVD
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Armando Santoro, M.D.
role: Principal Investigator
affiliation: Humanitas Cancer Center - Department of Medical Oncology and Haematology
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country: Italy
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Hodgkin Disease