Clinical Research Directory

Breakthrough CMV Lung Transplant -Multicentre

Cytomegalovirus (CMV) infection is the most common opportunistic infection in lung transplantation leading to direct and indirect effects that can result in life threatening complications. The risk of CMV infection is highest when the recipient of the transplant has never been in contact with CMV (negative immunity) and the donor had previous contact with CMV (positive immunity). This is called CMV mismatch. For these lung transplant patients 6 to 12 months of prophylaxis with an antiviral called Valganciclovir is recommended. This antiviral can cause side effects like bone marrow toxicity and decrease in immune cells which can result in temporarily having to stop the treatment. Starting and stopping the prophylaxis may result in the CMV becoming resistant to the medication. While taking the prophylaxis it is possible to have a breakthrough of the CMV, this is often due to the development of resistance to the antiviral. The purpose of this study is to learn more about the rate of CMV breakthrough while on prophylaxis after lung transplantation in patients who are CMV mismatch. The investigators will also look at the rates of negative side effects caused by antiviral prophylaxis in this population.

Valganciclovir Prophylaxis Versus Preemptive Therapy for Cytomegalovirus in Living Donor Kidney Transplant Recipients

Cytomegalovirus (CMV) infection remains one of the most frequent infectious complications after kidney transplantation. In intermediate-risk recipients (seropositive, R+ recipient) of living donor kidney transplants, optimal prevention strategies remain debated, particularly in the setting of basiliximab-based induction therapy. This open-label clinical trial aims to compare the incidence of CMV infection or disease in intermediate-risk (R+) living donor kidney transplant recipients receiving valganciclovir prophylaxis versus a preemptive therapy strategy. All patients receive basiliximab-based immunosuppression as part of standard clinical practice. Participants were enrolled between March 1, 2024 and July 31, 2025. Patients are followed for 12 months post-transplantation to assess the primary outcome of CMV infection or disease. Secondary outcomes include graft function, acute rejection episodes, and other infectious complications. The results of this study may help define the optimal CMV prevention strategy in intermediate-risk living donor kidney transplant recipients under basiliximab-based immunosuppression.

Casting Light on HOst-cytomegaloviRUs Interaction in Solid Organ Transplantation

CMV disease remains the most frequent infectious complication post-transplant and it is associated to high morbidity and even mortality. Global efforts from both transplant physicians and researchers in the field is needed to better characterize the host-virus interactions in the transplant setting, with the aim of decreasing the burden of disease and improve the well-being of patients. "HORUS" (Casting light on HOst-cytomegaloviRUs interaction in Solid organ transplantation) study is a European research project, funded by the European Commission (Horizon Europe) involving 16 partners in seven European countries (France, Spain, Czech Republic, Belgium, Switzerland, Germany and Italy) aiming to better characterize the host-CMV interactions in SOT recipients. The first aim of HORUS study will be to build a European cohort of SOT recipients including clinical characterization and the constitution of a biocollection, which is the aim of HORUS cohort, in order to perform biological, immunological, gene expression, viral kinetics and deep viral genome characterization in the global European HORUS project to improve our understanding of the development of a CMV immune response in the context of immunosuppression.

Efficacy of Extended Letermovir Prophylaxis to Prevent CMV Reactivation in High-Risk Chinese Adults Undergoing Allogeneic HSCT

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), recipients are immunocompromised and at increased risk of complications, including cytomegalovirus (CMV) infection. International clinical guidelines for the management of CMV infection post-allo-HSCT recommend three main strategies: minimizing infection risk, prevention, and preemptive therapy. However, traditional antiviral agents have not been approved for CMV prophylaxis in allo-HSCT recipients and are associated with significant adverse effects and the development of resistance, leaving the CMV prevention needs of this patient population unmet. Recent studies have demonstrated that letermovir prevents potent and highly specific antiviral activity against CMV, and it has been approved for CMV prophylaxis within the first 100 days post-allo-HSCT. Furthermore, evidence suggests that extending letermovir administration up to 28 weeks further reduces the risk of CMV infection in the later post-transplant period without increasing drug-related mortality. In China, the post-allo-HSCT CMV prevention strategy faces challenges such as limited treatment options, unclear guideline recommendations, non-standardized drug usage in certain medical institutions, and insufficient monitoring. This study aims to provide robust, evidence-based support for the use of letermovir in high-risk CMV reactivation among adult allo-HSCT recipients, thereby broadening clinical treatment choices.

Phase 3 Randomized Trial for Refractory ADV or CMV Infection With Family Matched CTLs and Standard of Care (SOC) vs SOC Alone

Patients with refractory ADV or CMV infection post allogeneic stem cell transplant will be randomized to either Family donor-derived viral specific cytotoxic T lymphocytes (CTLs) plus standard of care (SOC) vs SOC alone.

T Cell Therapy of Opportunistic Cytomegalovirus Infection

The purpose of this study is to determine if a specific type of cell-based immunotherapy, using T-cells from a donor that are specific against cytomegalovirus (CMV) is feasible to treat infections by CMV. Adoptive T-cell therapy is an investigational (experimental) therapy that works by using the blood of a donor and selecting the T-cells that can respond against a specific infectious entity. These selected T-cells are then infused to the patient, to try to give the immune system the ability to fight the infection. Adoptive T-cell therapy is experimental because it is not approved by the Food and Drug Administration (FDA).

Letermovir (Prevymis) for CMV in Kidney and Pancreas Transplant Recipients

This study is designed to assess how effective letermovir is in preventing recurrence of cytomegalovirus (CMV) infection in adult kidney or kidney/pancreas transplant recipients who are UW Health patients. Participants will be in the study for about 6 months.

HCMV-miRNA Monitoring After Allogeneic Hematopoietic Stem Cell Transplantation Using PSTM-qPCR

Human cytomegalovirus (HCMV) infection is one of the most common and serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Standard monitoring uses HCMV DNA testing, but this method may not detect the virus early enough to guide timely treatment. This multicenter observational study will evaluate a new high-performance microRNA (miRNA) detection technology (PSTM-qPCR) for monitoring HCMV infection in allo-HSCT patients. Approximately 300 patients and their donors will be enrolled across several major transplant centers in China. Blood samples will be collected before and after transplantation to test for both HCMV-miRNA and HCMV-DNA. The study will compare the sensitivity and timing of miRNA detection with conventional DNA testing and explore whether miRNA can serve as an early biomarker of infection and related complications. The goal is to improve early diagnosis and management of HCMV infection, reduce infection-related complications, and ultimately improve survival outcomes in patients undergoing allo-HSCT.

Evaluation of Software for Interpreting Virological Results Indicated for the Diagnosis of Cytomegalovirus (CMV) Infection During Pregnancy and Intended for Health Professionals

Congenital cytomegalovirus (CMV) infection is the most common congenital infection with a birth prevalence of 0.4% in Europe. It is the leading non-genetic cause of sensorineural hearing loss and a major cause of neurodevelopmental disabilities. The risk of intrauterine transmission is highest when primary infection occurs during pregnancy. Primary CMV infection is asymptomatic or causes non-specific symptoms and only serology can diagnose it with certainty. The diagnosis of CMV infection is based on the combination of 2 or 3 serological markers and the interpretation of the results is more complex than for other infections and may require additional analyses and sometimes delay the diagnosis and the implementation of secondary prevention of CMV transmission to the fetus by the administration of valaciclovir. Indeed, the effectiveness of secondary prevention is conditioned by the early administration of treatment after the maternal primary infection. The National Reference Center for Congenital CMV Infections at Necker Hospital, in collaboration with the virology laboratory at Paul Brousse Hospital, has developed the MyCMV "expert" tool, which is a decision-making algorithm that allows the interpretation of CMV serology and CMV PCR results. The hypothesis of the study is that the use and provision of this MyCMV "expert" tool to health professionals (biologists, midwives and obstetricians) for the interpretation of virological results could avoid a delay in diagnosis and would allow patients to be referred more quickly to a prenatal diagnosis center for appropriate management of CMV infection. The aim of the study is to evaluate the rate of detection of primary CMV infection in the first trimester of pregnancy using the MyCMV tool compared with the reference method (results interpreted by the centre's expert investigator).

Viral Specific T-Lymphocytes to Treat Infection With Adenovirus, Cytomegalovirus or Epstein-Barr Virus in Patients With Compromised Immunity

The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥2/6 HLA-matched, viral specific T cells have efficacy against adenovirus, CMV, and EBV, in subjects who have previously received any type of allogeneic HCT or solid organ transplant (SOT), or have compromised immunity. Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products, and cost associated with products that may not be used limits their value. In this trial, we will evaluate viral specific T cells generated by gamma capture technology. Eligible patients will include HCT and/or SOT recipients, and/or patients with compromised immunity who have adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.

Virus Specific Cytotoxic T-Lymphocytes (CTLs) for Refractory Cytomegalovirus (CMV)

CMV cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children, adolescents and young adults (CAYA) with refractory cytomegalovirus (CMV) infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant. Funding Source: FDA OOPD

R-MVST Cells for Treatment of Viral Infections in Children and Young Adults

The primary objective is to determine the safety and feasibility of administering R-MVST cells to patients with refractory viral reactivation and/or symptomatic disease caused by Epstein Barr Virus (EBV), cytomegalovirus (CMV), adenovirus (ADV) or BK virus. R-MVST cells will be generated on-demand from the closest partially human leukocyte antigen (HLA)-matched (minimum haploidentical) healthy donors or from the original allo-transplant donor if available. The investigator will closely monitor the recipients for potential toxicities including graft-versus-host disease (GVHD) post-infusion. Secondary objectives are to determine the effect of R-MVST infusion on viral load, possible recovery of antiviral immunity post-infusion and for evidence of clinical responses and overall survival. Recipients will be monitored for secondary graft failure at day 28 post R-MVST infusion.

Anti-viral T-cell Therapy by Gamma Capture

The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥1/6 Human Leukocyte Antigens (HLA) -matched, viral specific T cells have efficacy against adenovirus, Cytomegalovirus (CMV), and Epstein Barr Virus (EBV) in subjects who have previously received any type of allogeneic Hematopoietic Cell transplant (HCT) or solid organ transplant (SOT) or have compromised immunity. Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products, and cost associated with products that may not be used limits their value. This trial will evaluate viral specific T cells generated by gamma capture technology. Eligible patients will include HCT and/or SOT recipients, and/or patients with compromised immunity who have adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.

Immunoglobiulin-specific Prophylaxis of Citomegalovirus Infections in Immunocompromised Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Human cytomegalovirus (CMV) is a globally prevalent, human-specific herpesvirus characterised by a lifelong latency after primary infection, an often asymptomatic reactivation and affecting up to 100% of adults based on region and age. CMV reactivation has serious risks for immunocompromised patients, especially those undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In these patients, CMV can lead to graft failure, multiorgan disease, increased risk of other infections, GVHD, post-transplant lymphoproliferative disorders, and higher transplant-related mortality (TRM). Although antiviral prophylaxis, CMV infection occurs in 38-80% of HSCT recipients, but current antiviral drugs are insufficiently effective and they are associated with adverse effects. Furthermore, treatment failure is due to the high genetic variability of CMV. The protective role of virus-specific antibodies remains under debate. Some studies suggest that high neutralizing antibody titers protect transplant recipients from CMV, while others highlight the importance of T-cell responses. However, recent animal studies showed that humoral immunity alone can prevent CMV reactivation, even without T or NK cells. In solid-organ transplant patients, antibody titers ≥480 have been linked to reduced infection, shorter treatment, and full protection from CMV disease. Although the use of anti-CMV immunoglobulin remains controversial, the IRCCS Burlo Garofolo has used it as post-transplant prophylaxis and second-line treatment for over a decade. The main objective of their study was to assess whether CMV-specific immunoglobulin prophylaxis reduces CMV incidence and severity in pediatric HSCT patients. Secondary goals included evaluating its effect on transplant outcomes and its efficacy across different ethnic groups. A population pharmacokinetic (POP/PK) study was also conducted to better understand the drug's distribution and elimination and to identify factors influencing its pharmacokinetics in patients.

Open Label Trial of Oral Letermovir for CMV Prophylaxis in Thoracic Transplant Recipients

Open label study to determine tolerability and efficacy of letermovir for CMV prophylaxis in heart and lung transplant recipients. The study hypotheses are: 1. Letermovir prophylaxis will be associated with similar rates of CMV infection as valganciclovir among heart and lung transplant recipients 2. Letermovir will be better tolerated than valganciclovir for CMV prophylaxis in heart and lung transplant recipients, with a higher proportion of days of completed therapy with correct dosing during the planned prophylaxis period 3. Letermovir will have a lower rate of neutropenia than valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients 4. Incorrect renal dosing will occur less frequently with letermovir than with valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients

Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation

The purpose of this study is to evaluate whether virus-specific T cell lines (VSTs) are safe and can effectively control three viruses (EBV, CMV, and adenovirus) in patients who have had a stem cell transplant and also in patients that have a primary immunodeficiency disorder with no prior stem cell transplant.

QuantiFERON-CMV Test in a Prediction for Colic Cytomegalovirus Reactivation During Ulcerative Colitis

CytoMegaloVirus (CMV) infection impairs evolution of Ulcerative Colitis (UC) leading to more severe and resistant to immunosuppressive therapies flare-up. CytoMegaloVirus (CMV) reactivation is assessed by the quantification of the CytoMegaloVirus (CMV) DeoxyriboNucleic Acid (DNA) load by real-time PCR (qPCR) in colonic biopsies; this assay is invasive and costly. The QuantiFERON-CytoMegaloVirus (QF-CMV) assay measures the immune response against CytoMegaloVirus (CMV) in a blood specimen.

Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients

This is a research study to test the tolerability and clinical effectiveness of the study drug, Letermovir (LET), when used as secondary prophylaxis following treatment of Cytomegalovirus (CMV) infection and disease in a solid organ transplant recipient. This study is an open label trial in which Letermovir will be prescribed to prevent the recurrence of CMV infection and disease in a solid organ transplant recipient following treatment of CMV infection or disease.

Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study

Liver transplantation is the only curative treatment of end-stage liver disease, and every year, around 60 patients undergo liver transplantation in Denmark. Immunosuppressive therapy is necessary to avoid rejection of the transplanted organ. Over 90% of adults have been infected with at least one herpesvirus, and it is characteristic for herpesviruses that after a first-time infection, the virus remains dormant in the body and may reactivate, particularly if the host is immunosuppressed. An effective immune response against reactivation depends highly on T cells, but T cells are suppressed by immunosuppressive drugs given to organ transplant recipients. Infections caused by herpesviruses are therefore very common in organ transplant recipients, and particularly two herpesviruses, cytomegalovirus (CMV) and varicella-zoster virus (VZV) pose challenges after transplantation. CMV causes significant morbidity in transplant recipients, contributes to increased mortality and may contribute to loss of the transplanted organ. CMV infections occur in around 40% of liver transplant recipients within a year of transplantation. VZV causes chickenpox at first-time infection and shingles at reactivation. VZV is the second-most common infection in transplant recipients and occurs in around 9% of liver transplant recipients each year. Organ transplant recipients are at higher risk for disseminated disease with complications compared to immunocompetent persons. A limited number of drugs exist that reduce the risk of and treat CMV infection, but they may cause significant adverse events, and drug resistance is emerging. To avoid CMV infection, some liver transplant recipients receive prophylactic therapy, but due to toxicity, new treatment modalities are warranted. This requires knowledge about herpesvirus specific T cell function in liver transplant recipients, which currently is limited. The aim of this study is to provide an in-depth description of the protective immune response and immunological risk factors for CMV and VZV infections in liver transplant recipients and to identify patients at high risk in order to provide a platform for future treatment modalities against CMV and VZV infections in liver transplant recipients.

A Study to Assess Safety and Feasibility of Direct Infusions of Donor-derived Virus-specific T-cells in Recipients of Hematopoietic Stem Cell Transplantation With Post-transplant Viral Infections Using the Cytokine Capture System®

To assess the feasibility of donor-derived interferon (IFN)-γ positive select-ed virus-specific T-cells using the cytokine capture system® (CCS) and the safety of subsequent infusion in recipients of hematopoietic stem cell transplantation (HSCT) with treatment refractory post-transplant viral infections. The CCS has already been successfully used in clinical studies in Germany and United Kingdom (UK).

R-MVST Cells for Treatment of Viral Infections

The primary objective is to determine the safety and feasibility of administering R-MVST cells to patients with refractory viral reactivation and/or symptomatic disease caused by Epstein Barr Virus (EBV), cytomegalovirus (CMV), adenovirus (ADV) or BK virus. R-MVST cells will be generated on-demand from the closest partially human leukocyte antigen (HLA)-matched (minimum haploidentical) healthy donors or from the original allo-transplant donor if available. The investigator will closely monitor the recipients for potential toxicities including graft-versus-host disease (GVHD) post-infusion. Secondary objectives are to determine the effect of R-MVST infusion on viral load, possible recovery of antiviral immunity post-infusion and for evidence of clinical responses and overall survival. Recipients will be monitored for secondary graft failure at day 28 post R-MVST infusion.

ATG Individualized Dosing Model in URD-PBSCT.

Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft-versus-host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, non-relapse mortality, and disease recurrence. A targeted dosing strategy was established based on ATG concentration monitoring and conducted a phase 2 trial to evaluate the safety and efficacy of the dosing strategy in adult unmanipulated haplo-PBSCT, a encouraging result was attained. In this trial, The ATG-targeted dosing strategy was extended to adult unrelated donor allogeneic hematopoietic stem cell transplantation, ATG was administered for 4 days (-5 days to -2 days) during conditioning. The ATG doses on-3 days and- 2days were adjusted by our dosing strategy to achieve the optimal ATG exposure. The primary endpoint was CMV reactivation on +180 days.

Non Primary HCMV Infection: Natural History and Immune Response

The goals of this observational study are: i) investigate the natural history of non-primary (i.e. reactivation and reinfection) HCMV infection in HCMV-seropositive Italian women and the relevant humoral and cell-mediated immune response; ii) reliably distinguish between reactivation and reinfection. Prerequisite of the study is the availability of a maternal HCMV strain at baseline (original strain) to which subsequent strains detected during follow-up are compared in order to distinguish between reactivation (original strain) or reinfection (new strain). To increase the likelihood of exposure to different HCMV strains, the study population is restricted to mothers of children attending day care centers.

Quantiferon CMV to Identify Treatment Need for Asymptomatic CMV Infection After Solid Organ Transplant (QUANTIFOT)

Context Cytomegalovirus (CMV) infection is a frequent and potentially severe event in solid organ transplant (SOT) recipients. Most of available treatment display adverse effects that limit their use. Therefore, in case of an infection, it is of primary importance to identify the patients at high risk of severe infection and/or disease, and who ill benefit the most from antiviral therapy. As CMV infection is mainly controlled by cellular immunity, measuring specific anti-CMV T lymphocyte immunity could be an interesting tool for identifying these at-risk individuals. One of these tests is the QuantiFERON-CMV (QF-CMV) assay (QuiagenTM, Courtabœuf, France). Aim of the study The aim of the study is to determine the extent to which the QF-CMV can be use to identify, among SOT recipients with a CMV viremia, those that may not need antiviral therapy. Methods Participation to the study will be proposed to SOT recipients with an asymptomatic CMV infection with a blood viral load between 1,000 and 15,000 IU/mL. The QF-CMV will be performed in included participants, and the result will be given or not to the clinician in charge (according to the attributed group through randomisation). * In the group without result communication, the clinician in charge will determine whether a treatment is needed according to the guidelines and the local practices. * in the group with result communication, the clinician in charge will be advised not to introduce antiviral therapy if the result is positive, and to determine whether a treatment is needed according to the guidelines and the local practices if the result is positive. In the following weeks, the viral load will be monitored, along with creatininemia, cell blood count, and kalemia (to detect antiviral adverse effect). The participants will be sampled: * 5 to 12 days after QF-CMV sampling (V2) ; * 7 to 14 days days after V2 (V3 - between D12 and D26) ; * 7 to 14 days days after V3 (V4 - between D19 and D40) . Endpoints The primary endpoint is the rate of uncontrolled infection 5 to 12 days after QF-CMV sampling, defined as follows: * Blood CMV viral load \>10,000 IU/mL \[4 log\]; * And/or increase in blood viral load ≥0.5 log IU/mL with CV otherwise \>5000 IU/mL; * And/or the onset of CMV disease. The secondary endpoint is the is the occurrence antiviral adverse effects (hematoxicity or nephrotoxicity).