<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/NCT04419441</url>
  </required_header>
  <id_info>
    <org_study_id>ICI-RT-01</org_study_id>
    <nct_id>NCT04419441</nct_id>
  </id_info>
  <brief_title>Immune Checkpoint Inhibitors and Radiotherapy in Relapsed/Refractory Hodgkin Lymphoma</brief_title>
  <acronym>ICI-RT-1</acronym>
  <official_title>Retrospective, Multicentric, Observational Study to Evaluate the Efficacy and Safety of the Combination of an Immune Checkpoint Inhibitor (ICI) and Radiotherapy (RT) in Patients With Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (cHL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ospedale Maggiore Di Trieste</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ospedale Maggiore Di Trieste</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an observational retrospective study to investigate the efficacy and safety of the&#xD;
      treatment with an immune checkpoint inhibitor (nivolumab or pembrolizumab) in combination&#xD;
      with radiotherapy in patients with relapsed/refractory classical Hodgkin lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In patients with relapsed/refractory Hodgkin lymphoma, treatment with immune checkpoint&#xD;
      inhibitors (ICIs), nivolumab and pembrolizumab, leads to 20-30% of complete remission (CR)&#xD;
      rate. This means that for the majority of patients a consolidation strategy is usually&#xD;
      offered, in order to reduce relapse rate.&#xD;
&#xD;
      Strategies to improve CR rates should therefore be implemented, including combination&#xD;
      treatments. In solid tumors, the combination of ICIs and radiotherapy led to higher response&#xD;
      rates without mjor toxicity concerns. Radiotherapy is an effective therapeutic option already&#xD;
      used in Hodgkin lymphoma patients, also in the setting of relapsed/refractory disease. In his&#xD;
      observational study we aim to evaluate the efficacy and safety of ICIs and radiotherapy&#xD;
      administered in combination in patients with relapsed/refractory Hodgkin lymphoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 24, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2020</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Complete remission (CR) rate measured according to Lugano and Lyric criteria by CT-PET (positron emission tomography / computer tomography) or CT (computer tomography) scan</measure>
    <time_frame>up to 2 months after the end of ICI or 3 months after the end of RT</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall response rate (ORR) measured according to Lugano and Lyric criteria by CT-PET or CT scan</measure>
    <time_frame>up to 2 months after the end of ICI or 3 months after the end of RT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>progression-free survival (PFS) measured according to Cheson 2007 response criteria</measure>
    <time_frame>from the start of the treatment until the date of documented progression or date of death from any cause, assessed up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>safety profile assessed by monitoring adverse events (AEs) and serious adverse events (SAEs) according to CTCAE v. 4.0</measure>
    <time_frame>through study completion, for an average of 1 year</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Hodgkin Lymphoma</condition>
  <condition>Immune Checkpoint Inhibitor</condition>
  <condition>Radiotherapy</condition>
  <arm_group>
    <arm_group_label>treated patients</arm_group_label>
    <description>patients with relapsed/refractory Hodgkin lymphoma who received a treatment with the combination of radiotherapy and an immune checkpoint inhibitor</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Immune checkpoint inhibitor</intervention_name>
    <description>concomitant administration of radiotherapy and immune checkpoint inhibitor</description>
    <arm_group_label>treated patients</arm_group_label>
    <other_name>radiotherapy</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population includes adult patients with relapsed/refractory Hodgkin lymphoma&#xD;
        treated in referral centers for haematology&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age ≥18 years&#xD;
&#xD;
          -  diagnosis of classical Hodgkin lymphoma, treated with one immune checkpoint inhibitor&#xD;
             (ICI) (nivolumab or pembrolizumab), as per label indication&#xD;
&#xD;
          -  having received a concomitant radiotherapy, as per clinical need (persistence of&#xD;
             localized disease, bulky disease, other reasons). &quot;Concomitant&quot; radiotherapy means a&#xD;
             treatment received during the administration of ICI, or during the 8 weeks that&#xD;
             precede or follow the start or the end of the treatment with ICI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Having received a treatment with an ICI and radiotherapy not &quot;concomitant&quot;, according&#xD;
             to the abovementioned definition&#xD;
&#xD;
          -  Having received any other anti-lymphoma treatments during the same period of time&#xD;
&#xD;
          -  Patients who have not been evaluated by CT-PET or CT at the end of the combination&#xD;
             therapy&#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>Francesco Zaja, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>SC Ematologia Ospedale Maggiore Trieste</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Francesco Zaja, Professor</last_name>
    <phone>+390403992888</phone>
    <email>francesco.zaja@asugi.sanita.fvg.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>SC Ematologia Ospedale Maggiore</name>
      <address>
        <city>Trieste</city>
        <zip>34100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francesco Zaja, Professor</last_name>
      <phone>+390403992888</phone>
      <email>francesco.zaja@asugi.sanita.fvg.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.</citation>
    <PMID>17242396</PMID>
  </reference>
  <reference>
    <citation>Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.</citation>
    <PMID>25113753</PMID>
  </reference>
  <reference>
    <citation>Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA, Hoos A, Barrington SF, Armand P. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016 Nov 24;128(21):2489-2496. doi: 10.1182/blood-2016-05-718528. Epub 2016 Aug 29.</citation>
    <PMID>27574190</PMID>
  </reference>
  <reference>
    <citation>Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Kuruvilla J, Savage KJ, Trneny M, Shipp MA, Kato K, Sumbul A, Farsaci B, Ansell SM. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018 May 10;36(14):1428-1439. doi: 10.1200/JCO.2017.76.0793. Epub 2018 Mar 27. Erratum In: J Clin Oncol. 2018 Sep 10;36(26):2748.</citation>
    <PMID>29584546</PMID>
  </reference>
  <reference>
    <citation>Chen R, Zinzani PL, Lee HJ, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Lin J, Kim E, Nahar A, Balakumaran A, Moskowitz CH. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019 Oct 3;134(14):1144-1153. doi: 10.1182/blood.2019000324. Epub 2019 Aug 13.</citation>
    <PMID>31409671</PMID>
  </reference>
  <reference>
    <citation>Constine LS, Yahalom J, Ng AK, Hodgson DC, Wirth A, Milgrom SA, Mikhaeel NG, Eich HT, Illidge T, Ricardi U, Dieckmann K, Moskowitz CH, Advani R, Mauch PM, Specht L, Hoppe RT. The Role of Radiation Therapy in Patients With Relapsed or Refractory Hodgkin Lymphoma: Guidelines From the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2018 Apr 1;100(5):1100-1118. doi: 10.1016/j.ijrobp.2018.01.011. Epub 2018 Jan 9.</citation>
    <PMID>29722655</PMID>
  </reference>
  <reference>
    <citation>Chen L, Douglass J, Kleinberg L, Ye X, Marciscano AE, Forde PM, Brahmer J, Lipson E, Sharfman W, Hammers H, Naidoo J, Bettegowda C, Lim M, Redmond KJ. Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):916-925. doi: 10.1016/j.ijrobp.2017.11.041. Epub 2017 Dec 5.</citation>
    <PMID>29485071</PMID>
  </reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>September 14, 2020</last_update_submitted>
  <last_update_submitted_qc>September 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ospedale Maggiore Di Trieste</investigator_affiliation>
    <investigator_full_name>Francesco Zaja</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <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>Immune Checkpoint Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>it is not yet known if there will be a plan to make IPD available</ipd_description>
  </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/NCT04419441
org study id: ICI-RT-01
nct id: NCT04419441
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is an observational retrospective study to investigate the efficacy and safety of the
      treatment with an immune checkpoint inhibitor (nivolumab or pembrolizumab) in combination
      with radiotherapy in patients with relapsed/refractory classical Hodgkin lymphoma.
In patients with relapsed/refractory Hodgkin lymphoma, treatment with immune checkpoint
      inhibitors (ICIs), nivolumab and pembrolizumab, leads to 20-30% of complete remission (CR)
      rate. This means that for the majority of patients a consolidation strategy is usually
      offered, in order to reduce relapse rate.

      Strategies to improve CR rates should therefore be implemented, including combination
      treatments. In solid tumors, the combination of ICIs and radiotherapy led to higher response
      rates without mjor toxicity concerns. Radiotherapy is an effective therapeutic option already
      used in Hodgkin lymphoma patients, also in the setting of relapsed/refractory disease. In his
      observational study we aim to evaluate the efficacy and safety of ICIs and radiotherapy
      administered in combination in patients with relapsed/refractory Hodgkin lymphoma.
observational model: Case-Only
time perspective: Retrospective
measure: Complete remission (CR) rate measured according to Lugano and Lyric criteria by CT-PET (positron emission tomography / computer tomography) or CT (computer tomography) scan
time frame: up to 2 months after the end of ICI or 3 months after the end of RT
measure: overall response rate (ORR) measured according to Lugano and Lyric criteria by CT-PET or CT scan
time frame: up to 2 months after the end of ICI or 3 months after the end of RT
measure: progression-free survival (PFS) measured according to Cheson 2007 response criteria
time frame: from the start of the treatment until the date of documented progression or date of death from any cause, assessed up to 5 years
measure: safety profile assessed by monitoring adverse events (AEs) and serious adverse events (SAEs) according to CTCAE v. 4.0
time frame: through study completion, for an average of 1 year
arm group label: treated patients
description: patients with relapsed/refractory Hodgkin lymphoma who received a treatment with the combination of radiotherapy and an immune checkpoint inhibitor
intervention type: Drug
intervention name: Immune checkpoint inhibitor
description: concomitant administration of radiotherapy and immune checkpoint inhibitor
arm group label: treated patients
other name: radiotherapy
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Francesco Zaja, Professor
role: Principal Investigator
affiliation: SC Ematologia Ospedale Maggiore Trieste
last name: Francesco Zaja, Professor
phone: +390403992888
email: francesco.zaja@asugi.sanita.fvg.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
PMID: 17242396
citation: Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
PMID: 25113753
citation: Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA, Hoos A, Barrington SF, Armand P. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016 Nov 24;128(21):2489-2496. doi: 10.1182/blood-2016-05-718528. Epub 2016 Aug 29.
PMID: 27574190
citation: Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Kuruvilla J, Savage KJ, Trneny M, Shipp MA, Kato K, Sumbul A, Farsaci B, Ansell SM. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018 May 10;36(14):1428-1439. doi: 10.1200/JCO.2017.76.0793. Epub 2018 Mar 27. Erratum In: J Clin Oncol. 2018 Sep 10;36(26):2748.
PMID: 29584546
citation: Chen R, Zinzani PL, Lee HJ, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Lin J, Kim E, Nahar A, Balakumaran A, Moskowitz CH. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019 Oct 3;134(14):1144-1153. doi: 10.1182/blood.2019000324. Epub 2019 Aug 13.
PMID: 31409671
citation: Constine LS, Yahalom J, Ng AK, Hodgson DC, Wirth A, Milgrom SA, Mikhaeel NG, Eich HT, Illidge T, Ricardi U, Dieckmann K, Moskowitz CH, Advani R, Mauch PM, Specht L, Hoppe RT. The Role of Radiation Therapy in Patients With Relapsed or Refractory Hodgkin Lymphoma: Guidelines From the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2018 Apr 1;100(5):1100-1118. doi: 10.1016/j.ijrobp.2018.01.011. Epub 2018 Jan 9.
PMID: 29722655
citation: Chen L, Douglass J, Kleinberg L, Ye X, Marciscano AE, Forde PM, Brahmer J, Lipson E, Sharfman W, Hammers H, Naidoo J, Bettegowda C, Lim M, Redmond KJ. Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):916-925. doi: 10.1016/j.ijrobp.2017.11.041. Epub 2017 Dec 5.
PMID: 29485071
responsible party type: Principal Investigator
investigator affiliation: Ospedale Maggiore Di Trieste
investigator full name: Francesco Zaja
investigator title: Professor
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Immune Checkpoint Inhibitors
sharing ipd: Undecided
ipd description: it is not yet known if there will be a plan to make IPD available