NCT06812598

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

A Clinical Study on the Efficacy of Extended Letermovir Prophylaxis to Prevent CMV Reactivation in High-Risk Chinese Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 330 (estimated)
• Sponsor: The First Affiliated Hospital of Soochow University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

CMV late-onset infections following the discontinuation of letermovir have been reported in numerous clinical studies. During this period, transplant recipients remain in the critical phase of immune reconstitution, and further reducing the occurrence of CMV late-onset infections is crucial for improving transplant outcomes. International data have shown that extending the duration of letermovir prophylaxis can further reduce the risk of CMV infection. In high-risk populations for CMV reactivation and recurrence, the risk of CMV viremia remains elevated even beyond 100 days post-transplant, with incidence rates ranging from 36% to 54%. Consequently, clinical guidelines recommend extending prophylaxis duration, monitoring periods, and shortening the intervals between tests for these high-risk groups. The Chinese Expert Consensus on the Management of CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation (2022 Edition) suggests that for high-risk populations, particularly those with acute or chronic GVHD, consideration should be given to extending the treatment course or reinitiating CMV reactivation prevention until immunosuppressive therapy is reduced. Currently, in China, there are no prospective clinical studies or high-level evidence regarding the extension of prophylactic therapy to reduce CMV late-onset infections in adult allo-HSCT recipients at high risk for CMV reactivation. This study aims to investigate the efficacy and safety of extending letermovir prophylaxis from week 14 to week 24 post-HSCT in patients at high risk of CMV reactivation, thereby offering additional therapeutic options for these patients.

Conditions

• Cytomegalovirus Infections
• CMV

Interventions

Type	Name	Description
DRUG	Letermovir (0-24w）	Patients will begin receiving prophylactic treatment with domestically produced letermovir from day 0 to day 28 post-allo-HSCT, at a dose of 480 mg, administered orally once daily. If used in combination with cyclosporine, the dose should be reduced to 240 mg once daily. The treatment will continue until 24 weeks post-transplant (approximately 170 days).
DRUG	Letermovir (0-14w）	Patients will begin receiving prophylactic treatment with domestically produced letermovir from day 0 to day 28 post-allo-HSCT, at a dose of 480 mg, administered orally once daily. If used in combination with cyclosporine, the dose should be reduced to 240 mg once daily. The treatment will continue until 14 weeks post-transplant (approximately 100 days).

Timeline

• Start date: 2024-12-16
• Primary completion: 2026-06-01
• Completion: 2026-12-31
• First posted: 2025-02-06
• Last updated: 2026-01-21

Locations

1 site across 1 country: China