View clinical trials related to CMV Infection.
Filter by:The two main cytomegalovirus (CMV) prevention strategies are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT), but is associated with high rates of neutropenia and late onset of post-prophylactic disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients, but is rarely used after solid organ transplant recipients due to logistical considerations.
This is a single-center, non-interventional, retrospective study of data, at the level of the individual without identification, extracted from medical records of adult patients undergoing a kidney transplant procedure after 1st from January 2018 until reaching the sample size enrollment (around 500 individuals); this refers to the period of verification of individuals' eligibility for entry into the study. Individuals under strategy preemptive patients who developed CMV infection/disease within 12 months after transplantation. The data will be collected from date of transplant (including pre-transplant clinical history) until completion of at least 12 months after transplantation, or until graft loss, or recipient death or loss to follow-up, when/if applicable.
To evaluate the safety and tolerability of partial HLA-matched VSTs against both CMV and EBV viruses in recipients of allogeneic hematopoietic stem cells with refractory viral infections (CMV and/or EBV). Preliminary evaluation of the efficacy of partial HLA-matched VSTs against both CMV and EBV viruses in recipients of allogeneic hematopoietic stem cells with refractory viral infections (CMV and/or EBV); To monitor the duration and expansion of multi-virus VSTs cells after infusion.
Letermovir for the Prevention of CMV Infection in HSCT Recipients Based on the Outcome of mNGS
In the 30 years fighting against CMV infection, the mortality rate of HSCT patients was significantly reduced. Now we should turn to how to better improve the prognosis of HSCT patients and prevent CMV infection. The emergence of letermovir gave this vision a shot in the arm11-13. Letermovir is the only drug with an indication approved for the prevention of CMV infection in HSCT patients, with a novel mechanism of action characterized by inhibition of the CMV DNA terminase complex. The efficacy and safety of letermovir were well demonstrated in key phase III studies, where letermovir prophylaxis significantly reduced CMV infection and all-cause mortality after HSCT without increased myelosuppression and increased nephrotoxicity (vs. placebo)13. A real-world study of letermovir prophylaxis showed a significant reduction in CMV infection rates (47.0% vs 10.7%), and a significant reduction in antiviral use after 180 days. After more than100 days of continuous use, in addition to a significant reduction in clinically significant CMV infections and patients' overall survival increased, significant efficacy was consistently maintained in patients with grade 2 or greater GVHD14-17. A systematic review and meta-analysis of real-world studies on primary prevention in letermovir was showed in EBMT 2022. A total of 48 real-world observational studies were included, and the results showed that the use of CMV primary prevention was effective in reducing the overall risk of CMV performance (including CMV reactivation, cs-CMV infection and CMV disease), all-cause mortality and non-relapse mortality at day 200 in adult HSCT recipients. At 100 days follow-up, CMV reactivation decreased by 87%, meanwhile clinically significant CMV infection by 91%, CMV disease decreased by 69%, CMV-related hospitalization decreased by 94%, and GVHD decreased by 48%18. Letermovir has achieved excellent therapeutic benefits globally but is still in its infancy in China. Letermovir obtained an implied license for a clinical trial in June 2020, and in November 2020, Letermovir submitted and accepted four new drug marketing applications in China, including injection and tablet formulations. On December 31, 2021, the China National Medical Products Administration (NMPA) approved letermovir for cytomegalovirus (CMV) seropositive adult recipients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) [R+] prevention of cytomegalovirus infection and cytomegalovirus disease. The commercial launch of letermovir is estimated to be in August 2022. Since the seropositive rate of CMV in the Chinese population is over 90%, it is not enough to judge whether CMV prevention is necessary depending on serology. In the past few years, with the increased number of only children in China, haploidentical stem cell transplantation (haplo-SCT) has been showing a steady expanding trend in China. Most hospitals' pretreatment methods use the Beijing protocol (including ATG) rather than post-transplant cyclophosphamide method to prevent GVHD, which also greatly increases the risk of CMV. To our knowledge, there is little published data focused on the efficacy of CMV prophylaxis for patients undergoing the haplo-SCT in China. A "real-life" evaluation of the new drug in terms of efficacy, emergence of resistance, tolerance related to CMV infection, is useful to propose recommendations on management strategies. Therefore, we would like to conduct a prospective observation study of CMV surveillance in haplo-SCT patients receiving letermovir prophylaxis in China, to evaluate the potential real-life effect of letermovir on efficacy, drug resistance emergence, tolerability, and CMV infection-related morbidity and mortality. This work contributes to recommendations regarding CMV management strategies, especially for patients at highest risk, i.e., CMV R+ haploidentical transplant recipients.
Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The course and outcome of CMV infection are different clinically, and the mechanism of CMV infection after transplantation has not been clarified. Reconstitution of cellular immunity after HSCT is a critical determinant of the control of CMV infection. Investigators will dynamically monitor the CMV-specific cellular immune reconstitution after HSCT，and analyze the clinical factors and therapy strategies affecting recovery of CMV-specific immunity during 1 year after HSCT.
Multicentre, observational, retrospective study to analyze the differences in CMVi pattern and recurrences between two groups of allogeneic HSCT patients (haplo vs no haplo HSCT), with intervention both postransplant cyclophosphamide as GvHD prophylaxis, using a database with information from historical clinic data.
This is a single centre, single arm, open-label, phase I study to evaluate the safety and effectiveness of CMV-TCR-T cell immunotherapy in treating refractory CMV infection after HSCT.
CMV infection in transplantation remains the most frequent infectious complication causing increased morbidity and mortality. International recommendations advocate prevention of this infection by instituting direct antiviral treatment or monitoring viral replication by PCR with the start of curative antiviral treatment when the DNAemia is positive. The risk of CMV infection varies according to the serostatus of the donor (D) and recipient (R) at the time of transplantation. In the absence of prophylaxis, CMV infection occurs in 60-80% of D+R-, 50-60% of D+R+ and 25-50% of D-R+. The humoral anti-CMV response is represented by the production of antibodies to envelope proteins (gB and gH) and to molecules involved in viral attachment and entry into target cells. However, the majority of CMV-specific antibodies do not have antiviral neutralising activity. The investigators have identified a new player in the specific anti-CMV response expressing the Fc RIIIa receptor (CD16), that interacts with anti-CMV immunoglobulins (Ig): the Tgamma-delta V delta 2-negative lymphocyte (LTgdVd2neg). This lymphocyte subpopulation shows persistent expansion in the peripheral blood of kidney transplant patients with CMV infection. These cells express an effector-memory phenotype (CD45RA+/CD27-). This expansion is associated with resolution of infection in patients. The investigators have shown that CD16 is specifically and constitutively expressed on the surface of CMV-induced LTgdVd2neg in healthy volunteers and kidney transplant patients. The investigators have observed that one of the antiviral activities of anti-CMV IgG lies in its binding to the Fc RIIIa receptor (CD16) on the surface of LTgdVd2neg. The anti-CMV IgGs capturing virions thus activate CD16+ LTgdVd2neg with production of IFN interferon which in turn is responsible for inhibition of CMV viral multiplication. Anti-CMV IgG is a recommended therapeutic option, with a marketing authorisation for the prevention of CMV infection in kidney transplantation in Europe and a Temporary Authorisation for Use in France. Thus, R+ patients expressing a significant level of LTgdVd2neg CD16+ at D0 of transplantation could be protected against CMV, in the absence of direct antiviral treatment by the addition of anti-CMV Ig.
Haematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Adoptive transfer of virus-specific T cells is an attractive approach to restore protective T-cell immunity in patients with refractory viral infections after allogeneic HSCT. The aim of this Phase III trial is to confirm efficacy of this treatment in children and adults.