<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/NCT03806764</url>
  </required_header>
  <id_info>
    <org_study_id>CReSCT</org_study_id>
    <nct_id>NCT03806764</nct_id>
  </id_info>
  <brief_title>Cytomegalovirus (CMV) Reactivation in Allogeneic HSCT Recipient</brief_title>
  <acronym>CReSCT</acronym>
  <official_title>Assessing the Impact and Complications of Cytomegalovirus (CMV) Reactivation in a Multi-site Study of Allogeneic Haematopoietic Stem Cell Transplant Recipient</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Melbourne Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Peter MacCallum Cancer Centre, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Western Sydney Local Health District</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Walter and Eliza Hall Institute of Medical Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Austin Hospital, Melbourne Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Melbourne Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study consists of two parts: 1) Part 1, a retrospective part on 250 consecutive patients&#xD;
      following allogeneic haematopoietic stem cell transplant (allo-HSCT) at the Royal Melbourne&#xD;
      Hospital from 2012 to 2017, inclusive, and 2) Part 2, a prospective part on 120 allo-HSCT&#xD;
      patients from 4 sites in Australia: the Royal Melbourne Hospital, Peter MacCallum Cancer&#xD;
      Centre, Austin Hospital, and Westmead Hospital.&#xD;
&#xD;
      In Part 1, medical records of allo-HSCT recipients will be evaluated to determine the&#xD;
      incidence and clinical outcomes of CMV viremia post HSCT, including both the direct (CMV&#xD;
      disease) and indirect (such as invasive fungal infection, other viral infections, bacterial&#xD;
      infection) effects on clinical outcomes.&#xD;
&#xD;
      In Part 2, allo-HSCT participants at risk of CMV disease will be assessed to determine the&#xD;
      association of host CMV-specific immunity with clinical management and outcomes over one year&#xD;
      post allo-HSCT.&#xD;
&#xD;
      The overall aims of the study are to establish if CMV infection in allo-HSCT patients are&#xD;
      associated with poor clinical outcomes; and whether measurement of immunological functions&#xD;
      could provide an early indicator to identify patients at risk and appropriate timing for&#xD;
      initiation of CMV treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cytomegalovirus (CMV) infection is recognised as one of the most common and important&#xD;
      infectious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT).&#xD;
      Despite the serious clinical implications of CMV reactivation, there is a paucity of data&#xD;
      informing clinicians on how to best identify 'at risk' patients, timely commencement of&#xD;
      management of the infection.&#xD;
&#xD;
      This study consists of two parts: 1) Part 1, a retrospective part, and 2) Part 2, a&#xD;
      prospective part.&#xD;
&#xD;
      In Part 1, a retrospective cohort of 250 recipients of allo-HSCT at the Royal Melbourne&#xD;
      Hospital will be reviewed. The study period will be between January 2012- December 2017,&#xD;
      inclusive. The follow up period will be 6 months from the day of transplantation (ie. day 0&#xD;
      to 180). Data on patient demographics (age, sex, ethnicity), primary indication for&#xD;
      transplantation, donor type (match, unmatched, minor mismatch, related or unrelated), graft&#xD;
      source (stem cell, bone marrow, umbilical cord) conditioning regimen (myeloablative reduced&#xD;
      intensity conditioning), graft versus host disease (GVHD) prophylaxis eg. T-cell depletion,&#xD;
      days to neutrophil recovery, occurrence of acute and chronic GVHD and the therapy for GVHD&#xD;
      (including steroid intensity, use of ATG etc.), associated bacterial and fungal infections,&#xD;
      relapse and mortality, will be collected for analyses. CMV-negative patients will be used as&#xD;
      control for economic comparisons.&#xD;
&#xD;
      In Part 2, 120 recipients of allo-HSCT will be recruited from 4 Australian hospitals (the&#xD;
      Royal Melbourne Hospital, Austin Hospital, Peter MacCallum Cancer Centre, and Westmead&#xD;
      Hospital). Participants will be reviewed pre-transplant, 6, 12, 24 and 52 weeks following&#xD;
      HSCT during routine clinical visits. Clinical assessment will be made such as CMV viremia,&#xD;
      transplant related complications and current medications. In addition, participants who are&#xD;
      at high risk of CMV will have study bloods taken to assess immune functions with&#xD;
      Quantiferon-CMV®, Quantiferon-Monitor® assay, CMV Elispot, peripheral blood mononuclear cells&#xD;
      (PBMCs) and plasma for storage at time-points of 0, 6 and 12 weeks +/- 2 weeks after&#xD;
      commencing anti-CMV treatment. The Quantiferon-Monitor® assay will be performed at the&#xD;
      additional time points of 4, 18 and 26 weeks following HSCT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">April 17, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>The study consists of a retrospective and a prospective parts on patients developing CMV infection post allogeneic haematopoeitic stem cell transplant.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and outcome of CMV viremia</measure>
    <time_frame>250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.</time_frame>
    <description>The incidence and outcome of clinically relevant CMV viremia post HSCT will be assessed</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Host CMV-specific T cell immunity and related clinical outcomes</measure>
    <time_frame>52 weeks following HSCT</time_frame>
    <description>Host CMV-specific T cell immunity status of 120 participants will be assessed prospectively against CMV related clinical outcomes to establish if correlations exist</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Low level CMV viremia</measure>
    <time_frame>250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.</time_frame>
    <description>Association of low level CMV viremia and the subsequent clinical outcomes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Economic cost for managing CMV infection</measure>
    <time_frame>250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.</time_frame>
    <description>The economic cost attributable to managing CMV infection and CMV disease will be evaluated to provide a picture of health economics of the infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMV viral load for initiation of treatment</measure>
    <time_frame>52 weeks following HSCT</time_frame>
    <description>CMV viral load will be assessed to determine an appropriate trigger to initiate treatment for CMV viremia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of host T cell function and risk of CMV infection</measure>
    <time_frame>52 weeks following HSCT</time_frame>
    <description>Association of low or inadequate global immune function (T-cell and TLR7 responses) will be correlated with an increased risk of developing CMV infection post HSCT</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">370</enrollment>
  <condition>Cytomegalovirus Infections</condition>
  <condition>Haematological Malignancy</condition>
  <condition>Organ or Tissue Transplant; Complications</condition>
  <condition>Immune Suppression</condition>
  <arm_group>
    <arm_group_label>Retrospective study</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Medical records of 250 allo-HSCT recipients will be evaluated retrospectively to determine the incidence and clinical outcomes of CMV viremia post HSCT, including both the direct (CMV disease) and indirect (such as invasive fungal infection, other viral infections, bacterial infection) effects on clinical outcomes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prospective study</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>120 recipients of allo-HSCT will be recruited into the prospective part of the study. Participants will be reviewed pre-transplant, 6, 12, 24 and 52 weeks following HSCT during routine clinical visits. clinical assessment will be made such as CMV viremia, transplant related complications and current medications.&#xD;
Participants who are at high risk of CMV will have study blood sampling taken to assess immune functions</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood sampling</intervention_name>
    <description>Blood sampling from prospective study participants will be taken for immune functions measurements</description>
    <arm_group_label>Prospective study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For the retrospective cohort, all 250 consecutive allo-HSCT patients between 2012 to&#xD;
             2017 at the Royal Melbourne Hospital will be included, with CMV-negative patients&#xD;
             acting as controls for economic comparisons.&#xD;
&#xD;
          -  For the prospective cohort, patients undergoing allo-HSCT, at risk of CMV disease&#xD;
             (D+/R+, D-/R+ D+/R-), and able to provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For the retrospective cohort, no exclusion is set.&#xD;
&#xD;
          -  For the prospective cohort, patients who has CMV disease at the time of enrolment and&#xD;
             patients who are unable to provide informed consent.&#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>Monica Slavin, MBBS FRACP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Melbourne Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>May 30, 2023</last_update_submitted>
  <last_update_submitted_qc>May 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Melbourne Health</investigator_affiliation>
    <investigator_full_name>Monica Slavin</investigator_full_name>
    <investigator_title>Infectious Diseases Physician</investigator_title>
  </responsible_party>
  <keyword>Cytomegalovirus</keyword>
  <keyword>CMV</keyword>
  <keyword>Reactivation</keyword>
  <keyword>HSCT</keyword>
  <keyword>Stem cell transplant</keyword>
  <keyword>allogeneic</keyword>
  <keyword>immunosuppression</keyword>
  <keyword>viral infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytomegalovirus Infections</mesh_term>
    <mesh_term>Hematologic Neoplasms</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/NCT03806764
org study id: CReSCT
nct id: NCT03806764
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
This study consists of two parts: 1) Part 1, a retrospective part on 250 consecutive patients
      following allogeneic haematopoietic stem cell transplant (allo-HSCT) at the Royal Melbourne
      Hospital from 2012 to 2017, inclusive, and 2) Part 2, a prospective part on 120 allo-HSCT
      patients from 4 sites in Australia: the Royal Melbourne Hospital, Peter MacCallum Cancer
      Centre, Austin Hospital, and Westmead Hospital.

      In Part 1, medical records of allo-HSCT recipients will be evaluated to determine the
      incidence and clinical outcomes of CMV viremia post HSCT, including both the direct (CMV
      disease) and indirect (such as invasive fungal infection, other viral infections, bacterial
      infection) effects on clinical outcomes.

      In Part 2, allo-HSCT participants at risk of CMV disease will be assessed to determine the
      association of host CMV-specific immunity with clinical management and outcomes over one year
      post allo-HSCT.

      The overall aims of the study are to establish if CMV infection in allo-HSCT patients are
      associated with poor clinical outcomes; and whether measurement of immunological functions
      could provide an early indicator to identify patients at risk and appropriate timing for
      initiation of CMV treatment.
Cytomegalovirus (CMV) infection is recognised as one of the most common and important
      infectious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT).
      Despite the serious clinical implications of CMV reactivation, there is a paucity of data
      informing clinicians on how to best identify 'at risk' patients, timely commencement of
      management of the infection.

      This study consists of two parts: 1) Part 1, a retrospective part, and 2) Part 2, a
      prospective part.

      In Part 1, a retrospective cohort of 250 recipients of allo-HSCT at the Royal Melbourne
      Hospital will be reviewed. The study period will be between January 2012- December 2017,
      inclusive. The follow up period will be 6 months from the day of transplantation (ie. day 0
      to 180). Data on patient demographics (age, sex, ethnicity), primary indication for
      transplantation, donor type (match, unmatched, minor mismatch, related or unrelated), graft
      source (stem cell, bone marrow, umbilical cord) conditioning regimen (myeloablative reduced
      intensity conditioning), graft versus host disease (GVHD) prophylaxis eg. T-cell depletion,
      days to neutrophil recovery, occurrence of acute and chronic GVHD and the therapy for GVHD
      (including steroid intensity, use of ATG etc.), associated bacterial and fungal infections,
      relapse and mortality, will be collected for analyses. CMV-negative patients will be used as
      control for economic comparisons.

      In Part 2, 120 recipients of allo-HSCT will be recruited from 4 Australian hospitals (the
      Royal Melbourne Hospital, Austin Hospital, Peter MacCallum Cancer Centre, and Westmead
      Hospital). Participants will be reviewed pre-transplant, 6, 12, 24 and 52 weeks following
      HSCT during routine clinical visits. Clinical assessment will be made such as CMV viremia,
      transplant related complications and current medications. In addition, participants who are
      at high risk of CMV will have study bloods taken to assess immune functions with
      Quantiferon-CMV®, Quantiferon-Monitor® assay, CMV Elispot, peripheral blood mononuclear cells
      (PBMCs) and plasma for storage at time-points of 0, 6 and 12 weeks +/- 2 weeks after
      commencing anti-CMV treatment. The Quantiferon-Monitor® assay will be performed at the
      additional time points of 4, 18 and 26 weeks following HSCT.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: The study consists of a retrospective and a prospective parts on patients developing CMV infection post allogeneic haematopoeitic stem cell transplant.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Incidence and outcome of CMV viremia
time frame: 250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.
description: The incidence and outcome of clinically relevant CMV viremia post HSCT will be assessed
measure: Host CMV-specific T cell immunity and related clinical outcomes
time frame: 52 weeks following HSCT
description: Host CMV-specific T cell immunity status of 120 participants will be assessed prospectively against CMV related clinical outcomes to establish if correlations exist
measure: Low level CMV viremia
time frame: 250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.
description: Association of low level CMV viremia and the subsequent clinical outcomes
measure: Economic cost for managing CMV infection
time frame: 250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.
description: The economic cost attributable to managing CMV infection and CMV disease will be evaluated to provide a picture of health economics of the infection
measure: CMV viral load for initiation of treatment
time frame: 52 weeks following HSCT
description: CMV viral load will be assessed to determine an appropriate trigger to initiate treatment for CMV viremia
measure: Correlation of host T cell function and risk of CMV infection
time frame: 52 weeks following HSCT
description: Association of low or inadequate global immune function (T-cell and TLR7 responses) will be correlated with an increased risk of developing CMV infection post HSCT
arm group label: Retrospective study
arm group type: No Intervention
description: Medical records of 250 allo-HSCT recipients will be evaluated retrospectively to determine the incidence and clinical outcomes of CMV viremia post HSCT, including both the direct (CMV disease) and indirect (such as invasive fungal infection, other viral infections, bacterial infection) effects on clinical outcomes.
arm group label: Prospective study
arm group type: Other
description: 120 recipients of allo-HSCT will be recruited into the prospective part of the study. Participants will be reviewed pre-transplant, 6, 12, 24 and 52 weeks following HSCT during routine clinical visits. clinical assessment will be made such as CMV viremia, transplant related complications and current medications.
Participants who are at high risk of CMV will have study blood sampling taken to assess immune functions
intervention type: Diagnostic Test
intervention name: Blood sampling
description: Blood sampling from prospective study participants will be taken for immune functions measurements
arm group label: Prospective study
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Monica Slavin, MBBS FRACP
role: Principal Investigator
affiliation: Melbourne Health
facility: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: Melbourne Health
investigator full name: Monica Slavin
investigator title: Infectious Diseases Physician
mesh term: Cytomegalovirus Infections
mesh term: Hematologic Neoplasms