Letermovir Prophylaxis for CMV Infection in Haplo-HSCT Recipients: Single-center Data in China
- Conditions
- Hematopoietic Stem Cell TransplantationCMV Infection
- Interventions
- Registration Number
- NCT05789615
- Brief Summary
In the 30 years of fighting CMV infection, the mortality rate among HSCT patients has significantly reduced. Now, the focus is on improving the prognosis of HSCT patients and preventing CMV infection. The emergence of letermovir has provided a new opportunity in this regard. Letermovir, the only drug approved for CMV infection prevention in HSCT patients, works by inhibiting the CMV DNA terminase complex. Phase III studies have shown that letermovir significantly reduces CMV infection and all-cause mortality after HSCT, without increasing myelosuppression or nephrotoxicity. Real-world studies have further confirmed its efficacy in reducing CMV infection rates and antiviral use. Letermovir's global success has not yet been fully realized in China, where it is still in its early stages of use.
- Detailed Description
Letermovir achieved excellent therapeutic outcomes globally but is still developing in China. It received an implied license for clinical trials in June 2020, followed by marketing applications in November 2020. In December 2021, it was approved by the China National Medical Products Administration (NMPA) for preventing CMV infection and disease in CMV seropositive adult recipients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir's commercial launch in China is expected in August 2022. Given that over 90% of the Chinese population is CMV seropositive, determining whether CMV prevention is necessary based solely on serology is insufficient. The growing use of haploidentical stem cell transplantation (haplo-SCT) in China, particularly using the Beijing protocol for GVHD prevention, increases CMV risk. However, limited data exists on the efficacy of CMV prophylaxis for haplo-SCT patients in China. A real-life study assessing the efficacy, resistance, and tolerability of letermovir in this patient group is essential to guide CMV management strategies, particularly for high-risk CMV R+ haploidentical transplant recipients. This prospective study aims to evaluate letermovir's real-life impact on efficacy, resistance, tolerability, and CMV-related morbidity and mortality in China.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 200
- Haplo-SCT candidate (adult) who has decided to primary transplant and is willing to participate in the study.
- The haplo-SCT candidate (adult) should be CMV seropositive recipients.
- CMV-seronegative patient receiving a negative CMV donor graft.
- Patients having active CMV DNAemia at the time of letermovir initiation.
- Patient having signed the informed consent but not grafted.
- Patient recruited in a clinical study on an anti-CMV trial.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 200 haplo-HSCT recipients who are CMV seropositive Letermovir The study consists 200 cases CMV-R+ adult (\>18 years) recipients of haplo-HCT. All patients will receive letermovir prophylaxis. Consider a simple interim analysis of the experimental group could be arranged after 150 patients are enrolled if necessary. Supportive care is provided by institutional standards of care (e.g., acyclovir for herpes simplex virus and varicella zoster virus prevention). Letermovir prophylaxis is started on day 0 or no longer than 28 days after transplantation. During the study period, letermovir 480 mg PO/IV once daily (or 240 mg per day in patients taking cyclosporine) was administered from day 0 to day +100 post-HCT. CMV monitoring and preemptive therapy were performed according to local protocol. Plasma CMV viral load (VL) is monitored by quantitative CMV PCR, starting on day +7 and continued weekly until week 6, then every 2-4 weeks for months until week 24.
- Primary Outcome Measures
Name Time Method Incidence of clinically significant CMV infection at Week 14 following haplo-SCT Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease using classificatory criteria published by the Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. CMV DNA threshold for initiation of preemptive therapy at our center is viral load \>500 copies/mL or above on two consecutive tests.
- Secondary Outcome Measures
Name Time Method Incidence of clinically significant CMV infection through Week 24 following haplo-SCT Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease using classificatory criteria published by the Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. CMV DNA threshold for initiation of preemptive therapy at our center is viral load \>500 copies/mL or above on two consecutive tests.
Incidence of CMV DNAemia and CMV disease through Week 14 and Week 24 following haplo-SCT CMV DNAemia refers to the presence of CMV DNA in the blood. CMV disease refers to the organ dysfunction caused by an active CMV infection, such as the lungs, liver, and retina.
Incidence of the resistant or refractory CMV infection through Week 24 following haplo-SCT Resistant or refractory CMV infection occurs if CMV levels rise by 1 log after 2 weeks of treatment or remain positive after 4 weeks.
Incidence of serious adverse event leading to interruption of treatment through Week 24 following haplo-SCT Serious adverse events refers to events that require stopping the treatment to ensure patient safety.
Incidence of CMV-related disease mortality through Week 24 following haplo-SCT Death resulting directly or indirectly from complications of a CMV infection, often involving severe organ damage in the lungs, liver, or other organs.
Incidence of all-cause mortality and non-relapse mortality through Week 24 following haplo-SCT All-cause mortality refers to deaths from any cause, while non-relapse mortality refers to deaths caused by factors other than the recurrence or relapse of the original disease or condition.
Incidence of CMV-associated morbidity through Week 24 following haplo-SCT CMV-associated morbidity refers to organ damage, delay engraftment, acute or chronic GVHD occurrence, or other infectious diseases caused by CMV.
Incidence of rehospitalization through Week 14, Week 24 following haplo-HSCT The frequency or rate at which patients are readmitted to the hospital within a specified period following their discharge.
Trial Locations
- Locations (1)
The First Affiliated Hospital of Soochow university
🇨🇳Suzhou, Jiangsu, China