Letermovir Prophylaxis for Cytomegalovirus Infection in Haploidentical Allogeneic Hematopoietic Cell Transplant Recipients: Single-center Real-world Data in China
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Incidence of clinically significant CMV infection
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
200 haplo-HSCT recipients who are CMV seropositive
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.
干预措施: Letermovir (Drug)
结局指标
主要结局
Incidence of clinically significant CMV infection
时间窗: 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.
次要结局
- Incidence of clinically significant CMV infection(through Week 24 following haplo-SCT)
- Incidence of CMV DNAemia and CMV disease(through Week 14 and Week 24 following haplo-SCT)
- Incidence of the resistant or refractory CMV infection(through Week 24 following haplo-SCT)
- Incidence of serious adverse event leading to interruption of treatment(through Week 24 following haplo-SCT)
- Incidence of CMV-related disease mortality(through Week 24 following haplo-SCT)
- Incidence of all-cause mortality and non-relapse mortality(through Week 24 following haplo-SCT)
- Incidence of CMV-associated morbidity(through Week 24 following haplo-SCT)
- Incidence of rehospitalization(through Week 14, Week 24 following haplo-HSCT)