An interventional study of Letermovir and Comparator in Haematopoietic Stem Cell Transplantation, Antivirals and Cytomegalovirus Infections, sponsored by University Hospital, Limoges. Completed at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-09.
Sponsored by University Hospital, Limoges · Not applicable, Interventional, and Basic science
Cytomegalovirus (CMV) is a major cause of morbidity in hematopoietic stem cell transplant recipients, with both direct effects, including CMV disease, and indirect effects, such as graft-versus-host disease (GVHD) and increased immunosuppression.
Virological monitoring and preemptive treatment with ganciclovir have reduced the incidence of CMV disease from approximately 30% to 2-6%, but have not eliminated the indirect morbidity associated with viral replication. Letermovir, a non-hematotoxic antiviral agent targeting the CMV terminase complex, has demonstrated efficacy in preventing CMV infection in this population.
The CIRCLE study aims to describe the evolution of global and CMV-specific immune reconstitution in CMV-seropositive hematopoietic stem cell transplant recipients receiving or not receiving letermovir prophylaxis, and to characterize the immune response over time.
Cytomegalovirus (CMV) remains an important cause of morbidity in hematopoietic stem cell transplant recipients. Its effects include direct complications, such as CMV disease, and indirect complications, including graft-versus-host disease (GVHD) and increased immunosuppression.
Virological monitoring and preemptive treatment with ganciclovir have reduced the incidence of CMV disease from approximately 30% to 2-6%, but have not eliminated the indirect morbidity associated with viral replication. Before the availability of preventive treatment, CMV-related complications represented a substantial burden and were associated with an additional cost estimated at 25-30% of the total cost of transplantation (Robin et al., 2017).
Letermovir, an antiviral agent targeting the CMV terminase complex, has demonstrated efficacy as prophylaxis against CMV infection in hematopoietic stem cell transplant recipients (Marty et al., 2017). However, immune reconstitution during prophylaxis, which may help inform the duration of preventive treatment, requires further investigation. Previous publications have suggested a delay in CMV-specific immune reconstitution, but a comprehensive assessment of the immune response remains necessary.
The CIRCLE study is a prospective, multicenter ancillary study of the French NaViRe cohort (NCT04690933). It aims to describe global and CMV-specific immune reconstitution over time in CMV-seropositive hematopoietic stem cell transplant recipients receiving or not receiving letermovir prophylaxis. The study uses research and commercial assays to characterize immune responses and explore their potential relevance to routine patient monitoring.
A total of 50 patients are planned for inclusion: 25 receiving letermovir prophylaxis and 25 not receiving letermovir prophylaxis. Immune responses will be evaluated using immunological and virological assessments during follow-up after transplantation, including assessments up to 12 months after transplantation.
370 studies on the registry are indexed under Cytomegalovirus Infections; 57 are open to participants now.
This study's enrollment of 50 is below the median of 64 across 240 interventional studies indexed under Cytomegalovirus Infections.
Browse Cytomegalovirus Infections studies →University Hospital, Limoges is the lead sponsor of 264 studies on the registry; 38 are open to participants now.
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Exclusion Criteria:
CMV-seropositive hematopoietic stem cell transplant recipients receiving letermovir as primary prophylaxis and included in the NAViRe cohort. The study will describe overall and CMV-specific immune reconstitution, including its evolution during follow-up, using immunological and virological assessments.
Drug: Letermovir
Observational Cohort. CMV-seropositive hematopoietic stem cell transplant recipients included in the Cryostem cohort who did not receive letermovir as primary prophylaxis. The study will describe overall and CMV-specific immune reconstitution, including assessments before transplantation and at day 100 after transplantation.
Other: Comparator
Letermovir administered as primary prophylaxis against cytomegalovirus infection in CMV-seropositive hematopoietic stem cell transplant recipients, according to standard clinical practice.
CMV-seropositive hematopoietic stem cell transplant recipients included in the Cryostem cohort who did not receive letermovir as primary prophylaxis.
Viral load of torque teno virus (TTV) in whole blood
TTV viral load measured in whole blood and reported as copies/mL.
Time frame: Before transplantation (Day -30 to Day -8), Day 20, Month 3, Month 6, and Month 12 after transplantation.
Qualitative and functional assessment of natural killer (NK) cells
Qualitative and functional analysis of NK cells and measurement of CD74 RNA expression.
Time frame: Before transplantation (Day -30 to Day -8) and Day 100 after transplantation in patients not receiving letermovir prophylaxis.
CMV-specific cellular immune response
CMV-specific cellular immune response measured using QuantiFERON-CMV, ELISpot-CMV, and flow cytometry to quantify CMV-specific alpha-beta and gamma-delta T cells, including intracellular cytokine production and PD-1 receptor expression.
Time frame: Before transplantation (Day -30 to Day -8), Day 20, Month 3, Month 6, and one month after the end of letermovir prophylaxis, as applicable. An additional assessment will be performed one month after CMV reactivation, if applicable.
CMV-specific IgG concentration in plasma
Quantification of CMV-specific IgG antibodies in plasma.
Time frame: Before transplantation (Day -30 to Day -8), Day 20, Month 3, Month 6, and one month after the end of letermovir prophylaxis, as applicable.
Time to development of a significant CMV-specific cellular immune response
Time from transplantation to the first significant CMV-specific cellular immune response, defined by a positive QuantiFERON-CMV or ELISpot-CMV result according to the manufacturer's cut-offs, or detection of a CMV-specific T-cell response by flow cytometry following stimulation with CMV antigens.
Time frame: From before transplantation (Day -30 to Day -8) through Month 12 after transplantation.
Number of participants with CMV infection
Number of participants with CMV infection, defined by a positive diagnostic test for CMV detection without clinical symptoms.
Time frame: From before transplantation (Day -30 to Day -8) through Month 24 after transplantation.
Number of participants with CMV disease
Number of participants with CMV disease, defined as CMV infection associated with clinical symptoms and organ involvement.
Time frame: From before transplantation (Day -30 to Day -8) through Month 24 after transplantation.
Plan to share: Undecided
Ran from Sep 2022 to primary completion in Apr 2026, 43 months.
Of 23 interventional studies with no phase under Cytomegalovirus Infections, half reached primary completion within 40 months of starting (the median), counting those still running; a quarter within 24 and three quarters within 56. This study's 43 months is close to that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is completed, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Letermovir
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