Clinical trial NCT03806764: Cytomegalovirus (CMV) Reactivation in Allogeneic HSCT Recipient
Official title: Assessing the Impact and Complications of Cytomegalovirus (CMV) Reactivation in a Multi-site Study of Allogeneic Haematopoietic Stem Cell Transplant Recipient
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cytomegalovirus Infections
Haematological Malignancy
Organ or Tissue Transplant; Complications
Immune Suppression
Keywords: Cytomegalovirus
CMV
Reactivation
HSCT
Stem cell transplant
allogeneic
immunosuppression
viral infection
Lead sponsor: Melbourne Health
Sponsor class: OTHER
Collaborators: name: Peter MacCallum Cancer Centre, Australia
name: Western Sydney Local Health District
name: Walter and Eliza Hall Institute of Medical Research
name: Austin Hospital, Melbourne Australia
First posted: 2019-01-16
Enrollment: 370
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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

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.

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.

Eligibility 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.

Primary outcomes:
measure: Incidence and outcome of CMV viremia
timeFrame: 250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.
measure: Host CMV-specific T cell immunity and related clinical outcomes
timeFrame: 52 weeks following HSCT
Secondary outcomes:
measure: Low level CMV viremia
timeFrame: 250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.
measure: Economic cost for managing CMV infection
timeFrame: 250 retrospective cases of HSCTduring 2012 to 2017, inclusive, will be reviewed from the day of transplant to 6 months post transplant.
measure: CMV viral load for initiation of treatment
timeFrame: 52 weeks following HSCT
measure: Correlation of host T cell function and risk of CMV infection
timeFrame: 52 weeks following HSCT
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: Melbourne Health
name: Monica Slavin, MBBS FRACP
role: PRINCIPAL_INVESTIGATOR
References: