Evaluation of a laboratory test called QuantiFERON Cytomegalovirus in allogeneic stem cells transplant patients to assess its ability to detect the timing when the patients' immune system can control cytomegalovirus infection, thus allowing the clinical team the discontinuation of antiviral prophylaxis
| ISRCTN | ISRCTN13577788 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13577788 |
| IRAS number | 321427 |
| Secondary identifying numbers | RHM MED1935 |
- Submission date
- 09/05/2025
- Registration date
- 14/07/2025
- Last edited
- 14/07/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
This study is looking at a virus called CMV, which can cause serious illness in people who have had a stem cell transplant to treat blood cancers. These patients have weakened immune systems, making them more vulnerable to infections like CMV. The researchers want to find out if a special blood test (called QuantiFERON-CMV) can help doctors understand when a patient’s immune system is strong enough to stop CMV from causing illness. This could help doctors decide how long to give antiviral medication after a transplant.
Who can participate?
Adults (18 years or older) who are having a stem cell transplant to treat a blood cancer can take part. They must either already have CMV or be receiving stem cells from a donor who has CMV.
What does the study involve?
Participants will have a small amount of blood taken seven times over six months. The first sample is taken before the transplant begins, and the others are taken at regular intervals after the transplant (days 30, 60, 90, 120, 150, and 180). These samples will be used to test how well the immune system is recovering and responding to CMV.
What are the possible benefits and risks of participating?
There is no direct benefit to participants, but the results may help improve care for future patients. The main risk is the discomfort of having blood taken. The study team will try to take the blood samples during regular hospital visits to avoid extra appointments. If a patient’s doctor thinks it’s not safe to take blood (for example, if they are anaemic), the sample won’t be taken.
Where is the study run from?
The study is being run at University Hospital Southampton NHS Foundation Trust (UK).
When is the study starting and how long is it expected to run for?
August 2022 to August 2025.
Who is funding the study?
The study is funded by the Southampton Specialist Virology Centre, the Translational Immunology Group at the University of Southampton, and the University of Bournemouth (UK).
Who is the main contact?
Dr Emanuela Pelosi
Consultant Medical Virologist
Emanuela.Pelosi@uhs.nhs.uk
Contact information
Public, Principal Investigator
Southampton Specialist Virology Centre
Department of Infection
Tremona Road
Southampton General Hospital
Southampton
SO51 6YD
United Kingdom
 ORCID ID |
0000-0003-4970-1388 |
|---|---|
| Phone | +44 (0)2381205101 |
| Emanuela.Pelosi@uhs.nhs.uk |
Scientific
Department of Immunology
Bournemouth University
Fern Barrow
Poole
BH12 5BB
United Kingdom
| ORCID ID |
0000-0003-0913-8826 |
|---|---|
| Phone | +44 (0)1202 524111 |
| sbuchan@bournemouth.ac.uk |
Study information
| Study design | Single-centre prospective non-randomized open-label study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | 47312_PIS_V6_20Jun23.pdf |
| Scientific title | Evaluation of the clinical usefulness of QuantiFERON®-CMV assay in identifying when patients reconstitute their immunity against cytomegalovirus (CMV) after undergoing allogeneic HSCT: a prospective, non-randomised, open-label study |
| Study acronym | QF CMV |
| Study objectives | The risk of cytomegalovirus (CMV) reactivation and CMV disease in allogeneic-HSCT patients is correlated with the level of immunosuppression, which is highest during the first 3-4 months post-allogeneic HSCT. However, profound immunosuppression can be prolonged in patients suffering from graft versus host disease. The current standard of care for CMV infection, post allogeneic-HSCT, includes antiviral prophylaxis with Letermovir (to reduce to a minimum the risk of viral reactivation) and CMV DNA monitoring (to enable the administration of pre-emptive treatment, should viral reactivation occur). These two interventions are effective in managing CMV infection in the first few months post-HSCT. However, there is a caveat associated with Letermovir prophylaxis: the reduction of CMV reactivation rates during prophylaxis is followed by an increased incidence of late CMV disease and CMV-related mortality after day 100, when the drug is discontinued. This is likely due to a delay of CMV T-cell immune reconstitution due to the reduced viral reactivation and antigen stimulation of CMV-specific cytotoxic T-cells during prophylaxis (if the virus does not reactivate, there are no CMV antigens to stimulate CMV-specific cytotoxic T-cells). A delayed immune reconstitution is more remarkable in those patients on prolonged pharmacological immunosuppression due to the persistence of graft versus host disease. The inability to determine the timing of CMV immune reconstitution represents a diagnostic gap in the management of CMV infection post-allogeneic HSCT. The QuantiFERON®-CMV assay has the potential to address and close this gap by measuring CD8 T-cell IFN-g production in sequential samples post-HSCT. A reliable marker of immune reconstitution would be helpful for clinical decision making, such as the safe discontinuation of CMV DNA monitoring and antiviral prophylaxis. In addition, a negative QuantiFERON®-CMV assay result would provide important information regarding the patients’ risk of developing late CMV disease. We plan to perform QuantiFERON®-CMV assays in parallel with flow cytometry to confirm that QuantiFERON®-CMV assay results are correlated with the reconstitution of CMV-specific T-cell immunity. Several studies have been published so far documenting the clinical utility of the QuantiFERON®-CMV assay in allogeneic-HSCT recipients. These studies have been performed in several countries, including the USA, Australia, Germany, Italy, Greece and Korea. As far as we are aware, there are no published studies conducted in the United Kingdom. |
| Ethics approval(s) |
Approved 22/06/2023, Stratford Health Research Authority (2 Redman Place, Stratford, E20 1JQ, United Kingdom; +44 (0)20 7104 8049; approvals@hra.nhs.uk), ref: 23/LO/0366 |
| Health condition(s) or problem(s) studied | Cytomegalovirus immune reconstitution in recipients of allogeneic haematopoietic stem cell transplant |
| Intervention | The study aims to measure CMV-specific CD8+ lymphocyte function post-allogeneic-HSCT by using the QuantiFERON®-CMV assay on the DiaSorin Liaison XL Chemiluminescent diagnostic platform located in the Southampton Specialist Virology Centre. Flow cytometry studies, aimed to confirm the QuantiFERON®-CMV assay results, will be performed in the laboratory facilities of the University of Southampton. Patients will be recruited to the study during routine clinical visits by means of a short verbal explanation and the provision of an information sheet. Participants will sign a consent form. Signed consent forms will be scanned and stored in a secure, dedicated data file on the Virology hard drive. HSCT recipients will donate seven lithium heparin blood specimens that will be collected together with other blood samples that are part of the routine patient care post-HSCT. Blood samples will be collected every month for 6 months, with the first sample collected pre-HSCT, on the day patients commence the conditioning regimen. The seventh and last specimen will be collected 6 months post-allogeneic-HSCT. |
| Intervention type | Other |
| Primary outcome measure | 1. Risk of CMV disease is measured using the QuantiFERON-CMV assay on the DiaSorin Liaison XL platform at baseline (hospital admission before conditioning), and monthly until day 180 post-allogeneic-HSCT 2. IFN-gamma production in IU/mL is measured using the QuantiFERON-CMV assay at baseline and monthly until day 180 post-allogeneic-HSCT 3. Presence of CMV-specific CD8+ cells is measured using flow cytometry for CD3, CD4, CD8, CX3CR1, CCR7, and CD45RA at baseline and monthly until day 180 post-allogeneic-HSCT |
| Secondary outcome measures | 1. CMV immune reactivity is measured using the QuantiFERON-CMV assay at baseline and monthly until day 180 post-allogeneic-HSCT 2. CMV viral load is measured using weekly CMV DNA PCR testing from blood samples as part of standard of care from baseline until day 180 post-allogeneic-HSCT 3. CMV-specific CD8+ cell immunity is measured using the QuantiFERON-CMV assay at baseline and monthly until day 180 post-allogeneic-HSCT 4. Change in CMV viral load following reactivation is measured using CMV DNA PCR testing at the time of reactivation and in a follow-up blood sample collected 48–72 hours later |
| Overall study start date | 01/08/2022 |
| Completion date | 28/08/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 30 |
| Total final enrolment | 30 |
| Key inclusion criteria | 1. Age 18 years and over 2. Male or female 3. CMV IgG positive HSCT recipients, irrespective of the donor’s CMV IgG status 4. CMV IgG negative HSCT recipients with a CMV IgG positive donor |
| Key exclusion criteria | 1. CMV IgG negative HSCT recipient with a CMV IgG negative donor 2. Absence/withdrawal of consent |
| Date of first enrolment | 25/02/2024 |
| Date of final enrolment | 11/02/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Tremona Road
Southampton
SO16 6YD
United Kingdom
Sponsor information
Hospital/treatment centre
R&D Quality Assurance Manager, R&D Department
University Hospital Southampton NHS Foundation Trust
Tremona Road
Southampton
SO16 6YD
England
United Kingdom
| Phone | +44 (0)23 8120 5213 |
|---|---|
| sponsor@uhs.nhs.uk | |
| Website | https://www.uhs.nhs.uk/ |
"ROR" |
https://ror.org/0485axj58 |
Funders
Funder type
Hospital/treatment centre
Government organisation / Local government
- Location
- United Kingdom
Government organisation / Universities (academic only)
- Alternative name(s)
- University of Southampton UK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/08/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | Individual participant data from this study will be stored electronically on password protected data files on workstations within the Southampton Specialist Virology Centre by the investigators in a secure, access-controlled environment following the standard operating procedure of the UoS and a HTA licensed tissue bank until the final report of the project has been submitted and accepted for publication. The Chief Investigator will be the custodian of the data. Data will be collected and retained in accordance with the Data Protection Act 2018. The Chief Investigator and Co-Investigators will have access to the study data for analysis. Unidentifiable patients’ data will be analysed in the University Hospital Southampton and the University of Bournemouth (Dr Sarah Buchan, Co-Investigator, is a Principal Academic at the University of Bournemouth). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 6 | 20/06/2023 | 09/05/2025 | No | Yes |
Additional files
Editorial Notes
09/05/2025: Study's existence confirmed by the HRA.
