<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/NCT02991846</url>
  </required_header>
  <id_info>
    <org_study_id>GITMO-GVCrOSy</org_study_id>
    <nct_id>NCT02991846</nct_id>
  </id_info>
  <brief_title>A Prospective Observational Study for Evaluating CGVHD</brief_title>
  <acronym>GITMO-GVCrOSy</acronym>
  <official_title>A Prospective Observational Study for Evaluating Incidence, Severity and Outcomes of Chronic Graft-versus-Host Disease According to 2015 NIH Consensus Criteria</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gruppo Italiano Trapianto di Midollo Osseo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gruppo Italiano Trapianto di Midollo Osseo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prospective, observational, multicentre, spontaneous, non-interventional study This study&#xD;
      will evaluate all consecutive patients who develop chronic graft-versus-host disease,&#xD;
      reported by the Italian GITMO centers according to a standardized Web platform for real-time,&#xD;
      onsite data collection. The platform for data collection will be based on a software&#xD;
      prototype developed by the Clinica di Ematologia di Ancona Transplant Center for the&#xD;
      management of patients with chronic graft-versus-host disease. This software has been&#xD;
      integrated with algorithms that automatically determine: severity of chronic&#xD;
      graft-versus-host disease and overall response according to the 2015 NIH consensus criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic Graft-versus-Host Disease represents the first cause of transplant-related mortality&#xD;
      and reduced quality of life after transplant (HSCT). The epidemiology of Chronic&#xD;
      Graft-versus-Host Disease is largely unknown; moreover, diagnosis of Chronic&#xD;
      Graft-versus-Host Disease can be easily missed because its onset is often late in the&#xD;
      post-transplant period, requires specific follow up, and general practitioners are usually&#xD;
      not familiar with this entity. Successful treatment of Chronic Graft-versus-Host Disease&#xD;
      represents an unmet clinical need in the field of allogeneic transplantation. Steroids are&#xD;
      standard treatment, but up to 60% of the patients will require second-line treatment but&#xD;
      there is no standard second-line treatment for Chronic Graft-versus-Host Disease steroid&#xD;
      refractory. To help standardise the management Chronic Graft-versus-Host Disease, the NIH&#xD;
      Consortium proposed consensus definitions for diagnosis, scoring and response criteria in&#xD;
      2006 revised in 2015 which offers a shared framework to study this rare disease. These&#xD;
      criteria are not yet validated and thus not suitable for clinical trials.&#xD;
&#xD;
      This study is prospective, observational, multicentre, spontaneous, non-interventional study&#xD;
      that will evaluate all consecutive patients who develop chronic graft-versus-host disease,&#xD;
      reported by the Italian GITMO centers according to a standardized Web platform for real-time,&#xD;
      on-site data collection. The platform for data collection will be based on a software&#xD;
      prototype developed by the Ancona Transplant Center for the management of patients with&#xD;
      Chronic Graft-versus-Host Disease. This software has been integrated with algorithms that&#xD;
      automatically determine: severity of Chronic Graft-versus-Host Disease and overall response&#xD;
      by the 2015 NIH consensus criteria. Historical controls to compare Chronic Graft-versus-Host&#xD;
      Disease incidence, toxicities, response rate and hard outcomes will be used.&#xD;
&#xD;
      The aim of this project is to evaluate prospectively the long-term effectiveness of different&#xD;
      therapies by the hard outcome &quot;failure free survival&quot; commonly considered the most reliable&#xD;
      one. The failure free survival is the result of a number of factors that influence the&#xD;
      treatment failure and has been shown a reliable predictor of long-term survival. Main cause&#xD;
      of failure is the change in immunosuppressive treatment although recurrent disease, treatment&#xD;
      toxicity and mortality from Chronic Graft-versus-Host Disease (or other infectious&#xD;
      complications) also contribute to failure free survival. Second, we aim to evaluate the&#xD;
      prognostic ability of the latest NIH response criteria to predict main hard survival outcomes&#xD;
      and to assess their suitability as a tool for decision-making that ultimately leads to&#xD;
      treatment changes. Finally, we aim to evaluate the feasibility of the use of an electronic&#xD;
      tool for data collection in daily clinical practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">November 22, 2022</completion_date>
  <primary_completion_date type="Actual">November 22, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Failure free survival (FFS)</measure>
    <time_frame>Measured from the start of 1st line immunosuppressive treatment for cGVHD until the date of first documented progression or date of death from any cause whichever came first, assessed up to 1 years from transplant</time_frame>
    <description>To estimate the failure free survival measured from the start of 1st line immunosuppressive treatment for cGVHD, defined as the probability of survival free of any of the following events: cGVHD progression, need of a new immunosuppressive treatment, need of treatment dose escalation, relapse of the underlying hematological disease, severe (CTCAE grade 3-4) toxicity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rate (RR)</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Global and organ-specific response rate (RR), evaluated 3 and 6 months after starting systemic treatment, by the 2015 NIH criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and grade of cGVHD</measure>
    <time_frame>at 1 year from transplant</time_frame>
    <description>Incidence and grade of cGVHD, by the 2015 NIH criteria at 1 year after Hematopoietic stem cell transplantation (HSCT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>relapse</measure>
    <time_frame>1 year from transplant</time_frame>
    <description>Cumulative incidence of relapse of underlying haematological malignancy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>non-relapse mortality</measure>
    <time_frame>1 year from transplant</time_frame>
    <description>Cumulative incidence of non-relapse mortality (NRM), defined as any death not due to disease relapse or progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>treatment change</measure>
    <time_frame>measured from the start of first-line and subsequent treatment lines for 1 year</time_frame>
    <description>Cumulative incidence of treatment change, measured from the start of first-line and subsequent treatment lines</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Successful withdrawal of immunosuppressive treatment</measure>
    <time_frame>Measured from the start of firs-tline and subsequent treatment lines for 1 year</time_frame>
    <description>Cumulative incidence of successful withdrawal of immunosuppressive treatment, measured from the start of first-line and subsequent treatment lines.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>measured from cGVHD diagnosis until 1 year</time_frame>
    <description>Overall Survival, measured from cGVHD diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe Adverse Events (SAE) and Toxicities</measure>
    <time_frame>Measured from first treatment for cGVHD until 1 year</time_frame>
    <description>Incidence of Severe Adverse Events (SAE), toxicities (by the Common Terminology Criteria for Adverse Events - CTCAE), infections during treatments.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">248</enrollment>
  <condition>Chronic Graft-Versus-Host Disease</condition>
  <arm_group>
    <arm_group_label>Patients with cGVHD</arm_group_label>
    <description>All consecutive patients undergoing allogenic stem cell transplant for any underlying disease who develop chronic graft-versus-host disease (cGVHD)</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        All consecutive patients undergoing sllogenic stem cell transplant for any underlyng&#xD;
        disease who develop chronic graft-versus-host disease (cGVHD)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any age&#xD;
&#xD;
          -  All patients who develop cGVHD (any grade) by the NIH criteria after allogeneic&#xD;
             transplantation&#xD;
&#xD;
          -  Written and signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Absence of informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Attilio Olivieri, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AOU Ospedali Riuniti di Ancona</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Azienda Ospedaliera SS Antonio e Biagio</name>
      <address>
        <city>Alessandria</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Ospedali Riuniti</name>
      <address>
        <city>Ancona</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico di Bari-Ematologia con trapianti</name>
      <address>
        <city>Bari</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Divisione di Ematologia - Ospedali Papa Giovanni XXIII</name>
      <address>
        <city>Bergamo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Orsola</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Regionale Generale- Divisione Ematologia</name>
      <address>
        <city>Bolzano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AO Spedali Civili di Brescia- USD - TMO Adulti</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Ferrarotto - Ematologia</name>
      <address>
        <city>Catania</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle</name>
      <address>
        <city>Cuneo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cattedra di Ematologia - Azienda Ospedaliera di Careggi</name>
      <address>
        <city>Firenze</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Gaslini</name>
      <address>
        <city>Genova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osp. Card. Panico</name>
      <address>
        <city>Lecce</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Maggiore - Policlinico</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CTMO Fond MBBM Clinica pediatrica</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uoc Sit Tmo</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda ospedaliera Universitaria di Parma</name>
      <address>
        <city>Parma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale G. Da Saliceto di Piacenza</name>
      <address>
        <city>Piacenza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli</name>
      <address>
        <city>Reggio Calabria</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arciospedale S. M. Novella</name>
      <address>
        <city>Reggio Emilia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cattedra di Ematologia - Policlinico Umberto I</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. Citta della Salute e della Scienza</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Regina Margherita</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Santa Maria della Misericordia</name>
      <address>
        <city>Udine</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico GB Rossi</name>
      <address>
        <city>Verona</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Bortolo-Divisione Ematologia</name>
      <address>
        <city>Vicenza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>November 23, 2022</last_update_submitted>
  <last_update_submitted_qc>November 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic graft-versus-host disease cGVHD</keyword>
  <keyword>Hematopoietic stem cell transplantation HSCT</keyword>
  <keyword>NIH consensus criteria</keyword>
  <keyword>GITMO</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchiolitis Obliterans Syndrome</mesh_term>
    <mesh_term>Graft vs Host 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/NCT02991846
org study id: GITMO-GVCrOSy
nct id: NCT02991846
lead sponsor: 
has dmc: No
Prospective, observational, multicentre, spontaneous, non-interventional study This study
      will evaluate all consecutive patients who develop chronic graft-versus-host disease,
      reported by the Italian GITMO centers according to a standardized Web platform for real-time,
      onsite data collection. The platform for data collection will be based on a software
      prototype developed by the Clinica di Ematologia di Ancona Transplant Center for the
      management of patients with chronic graft-versus-host disease. This software has been
      integrated with algorithms that automatically determine: severity of chronic
      graft-versus-host disease and overall response according to the 2015 NIH consensus criteria.
Chronic Graft-versus-Host Disease represents the first cause of transplant-related mortality
      and reduced quality of life after transplant (HSCT). The epidemiology of Chronic
      Graft-versus-Host Disease is largely unknown; moreover, diagnosis of Chronic
      Graft-versus-Host Disease can be easily missed because its onset is often late in the
      post-transplant period, requires specific follow up, and general practitioners are usually
      not familiar with this entity. Successful treatment of Chronic Graft-versus-Host Disease
      represents an unmet clinical need in the field of allogeneic transplantation. Steroids are
      standard treatment, but up to 60% of the patients will require second-line treatment but
      there is no standard second-line treatment for Chronic Graft-versus-Host Disease steroid
      refractory. To help standardise the management Chronic Graft-versus-Host Disease, the NIH
      Consortium proposed consensus definitions for diagnosis, scoring and response criteria in
      2006 revised in 2015 which offers a shared framework to study this rare disease. These
      criteria are not yet validated and thus not suitable for clinical trials.

      This study is prospective, observational, multicentre, spontaneous, non-interventional study
      that will evaluate all consecutive patients who develop chronic graft-versus-host disease,
      reported by the Italian GITMO centers according to a standardized Web platform for real-time,
      on-site data collection. The platform for data collection will be based on a software
      prototype developed by the Ancona Transplant Center for the management of patients with
      Chronic Graft-versus-Host Disease. This software has been integrated with algorithms that
      automatically determine: severity of Chronic Graft-versus-Host Disease and overall response
      by the 2015 NIH consensus criteria. Historical controls to compare Chronic Graft-versus-Host
      Disease incidence, toxicities, response rate and hard outcomes will be used.

      The aim of this project is to evaluate prospectively the long-term effectiveness of different
      therapies by the hard outcome "failure free survival" commonly considered the most reliable
      one. The failure free survival is the result of a number of factors that influence the
      treatment failure and has been shown a reliable predictor of long-term survival. Main cause
      of failure is the change in immunosuppressive treatment although recurrent disease, treatment
      toxicity and mortality from Chronic Graft-versus-Host Disease (or other infectious
      complications) also contribute to failure free survival. Second, we aim to evaluate the
      prognostic ability of the latest NIH response criteria to predict main hard survival outcomes
      and to assess their suitability as a tool for decision-making that ultimately leads to
      treatment changes. Finally, we aim to evaluate the feasibility of the use of an electronic
      tool for data collection in daily clinical practice.
observational model: Cohort
time perspective: Prospective
measure: Failure free survival (FFS)
time frame: Measured from the start of 1st line immunosuppressive treatment for cGVHD until the date of first documented progression or date of death from any cause whichever came first, assessed up to 1 years from transplant
description: To estimate the failure free survival measured from the start of 1st line immunosuppressive treatment for cGVHD, defined as the probability of survival free of any of the following events: cGVHD progression, need of a new immunosuppressive treatment, need of treatment dose escalation, relapse of the underlying hematological disease, severe (CTCAE grade 3-4) toxicity.
measure: Response rate (RR)
time frame: 3 and 6 months
description: Global and organ-specific response rate (RR), evaluated 3 and 6 months after starting systemic treatment, by the 2015 NIH criteria
measure: Incidence and grade of cGVHD
time frame: at 1 year from transplant
description: Incidence and grade of cGVHD, by the 2015 NIH criteria at 1 year after Hematopoietic stem cell transplantation (HSCT)
measure: relapse
time frame: 1 year from transplant
description: Cumulative incidence of relapse of underlying haematological malignancy
measure: non-relapse mortality
time frame: 1 year from transplant
description: Cumulative incidence of non-relapse mortality (NRM), defined as any death not due to disease relapse or progression
measure: treatment change
time frame: measured from the start of first-line and subsequent treatment lines for 1 year
description: Cumulative incidence of treatment change, measured from the start of first-line and subsequent treatment lines
measure: Successful withdrawal of immunosuppressive treatment
time frame: Measured from the start of firs-tline and subsequent treatment lines for 1 year
description: Cumulative incidence of successful withdrawal of immunosuppressive treatment, measured from the start of first-line and subsequent treatment lines.
measure: Overall Survival
time frame: measured from cGVHD diagnosis until 1 year
description: Overall Survival, measured from cGVHD diagnosis.
measure: Severe Adverse Events (SAE) and Toxicities
time frame: Measured from first treatment for cGVHD until 1 year
description: Incidence of Severe Adverse Events (SAE), toxicities (by the Common Terminology Criteria for Adverse Events - CTCAE), infections during treatments.
arm group label: Patients with cGVHD
description: All consecutive patients undergoing allogenic stem cell transplant for any underlying disease who develop chronic graft-versus-host disease (cGVHD)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Attilio Olivieri, MD
role: Principal Investigator
affiliation: AOU Ospedali Riuniti di Ancona
facility: 
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country: Italy
responsible party type: Sponsor
mesh term: Bronchiolitis Obliterans Syndrome
mesh term: Graft vs Host Disease