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Cytomegalovirus (CMV) Reactivation in Allogeneic HSCT Recipient (CReSCT)

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ClinicalTrials.gov Identifier: NCT03806764
Recruitment Status : Enrolling by invitation
First Posted : January 16, 2019
Last Update Posted : January 16, 2019
Sponsor:
Collaborators:
Peter MacCallum Cancer Centre, Australia
Western Sydney Local Health District
Walter and Eliza Hall Institute of Medical Research
Austin Hospital, Melbourne Australia
Information provided by (Responsible Party):
Monica Slavin, Melbourne Health

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Cytomegalovirus Infections Haematological Malignancy Organ or Tissue Transplant; Complications Immune Suppression Diagnostic Test: Blood sampling Not Applicable

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 370 participants
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.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Assessing the Impact and Complications of Cytomegalovirus (CMV) Reactivation in a Multi-site Study of Allogeneic Haematopoietic Stem Cell Transplant Recipient
Actual Study Start Date : April 17, 2018
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Retrospective study
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.
Prospective study

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

Diagnostic Test: Blood sampling
Blood sampling from prospective study participants will be taken for immune functions measurements




Primary Outcome Measures :
  1. 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. ]
    The incidence and outcome of clinically relevant CMV viremia post HSCT will be assessed

  2. Host CMV-specific T cell immunity and related clinical outcomes [ Time Frame: 52 weeks following HSCT ]
    Host CMV-specific T cell immunity status of 120 participants will be assessed prospectively against CMV related clinical outcomes to establish if correlations exist


Secondary Outcome Measures :
  1. 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. ]
    Association of low level CMV viremia and the subsequent clinical outcomes

  2. 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. ]
    The economic cost attributable to managing CMV infection and CMV disease will be evaluated to provide a picture of health economics of the infection

  3. CMV viral load for initiation of treatment [ Time Frame: 52 weeks following HSCT ]
    CMV viral load will be assessed to determine an appropriate trigger to initiate treatment for CMV viremia

  4. Correlation of host T cell function and risk of CMV infection [ Time Frame: 52 weeks following HSCT ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For the retrospective cohort, all 250 consecutive allo-HSCT patients between 2012 to 2017 at the Royal Melbourne Hospital will be included, with CMV-negative patients acting as controls for economic comparisons.
  • For the prospective cohort, patients undergoing allo-HSCT, at risk of CMV disease (D+/R+, D-/R+ D+/R-), and able to provide informed consent.

Exclusion Criteria:

  • For the retrospective cohort, no exclusion is set.
  • For the prospective cohort, patients who has CMV disease at the time of enrolment and patients who are unable to provide informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03806764


Locations
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Australia, Victoria
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Sponsors and Collaborators
Melbourne Health
Peter MacCallum Cancer Centre, Australia
Western Sydney Local Health District
Walter and Eliza Hall Institute of Medical Research
Austin Hospital, Melbourne Australia
Investigators
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Principal Investigator: Monica Slavin, MBBS FRACP Melbourne Health

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Responsible Party: Monica Slavin, Infectious Diseases Physician, Melbourne Health
ClinicalTrials.gov Identifier: NCT03806764     History of Changes
Other Study ID Numbers: CReSCT
First Posted: January 16, 2019    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Monica Slavin, Melbourne Health:
Cytomegalovirus
CMV
Reactivation
HSCT
Stem cell transplant
allogeneic
immunosuppression
viral infection

Additional relevant MeSH terms:
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Cytomegalovirus Infections
Hematologic Neoplasms
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Neoplasms by Site
Neoplasms
Hematologic Diseases