A Study of the Drug Letermovir as Prevention of Cytomegalovirus Infection After Stem Cell Transplant in Pediatric Patients

PRIMARY OBJECTIVE: I. To evaluate the efficacy of letermovir prophylaxis in the prevention of clinically significant CMV infection through Week 14 (\~100 days) post-transplant in children and adolescents receiving allogeneic hematopoietic cell transplant (allo-HCT). SECONDARY OBJECTIVE: I. To evaluate the efficacy of letermovir prophylaxis as assessed by CMV-free survival through 24 weeks (\~6 months) post-transplant in pediatric patients. EXPLORATORY OBJECTIVES: I. To evaluate the incidence of clinically significant CMV infection through 24 and 52 weeks post-transplant in patients who receive letermovir prophylaxis. II. To evaluate overall survival post-transplant in patients who receive letermovir prophylaxis. III. To evaluate time to engraftment and describe the cumulative incidence of non-engraftment among patients who receive letermovir. IV. To examine the following clinically significant adverse events among patients exposed to letermovir: the total duration of neutropenia through week 14 (\~100 days) post-transplant, the cumulative incidence of acute kidney injury and chronic kidney disease by 52 weeks post-transplant, and total inpatient hospital days by 14 weeks (\~100 days) and 52 weeks post-transplant. V. Describe patterns of anti-viral resistance at the onset of CMV DNAemia after allo-HCT among patients who receive letermovir prophylaxis. VI. To describe immune reconstitution and CMV-specific immunity among patients who receive letermovir prophylaxis. OUTLINE: Enrolled patients will be added to the single arm of the study and receive letermovir prophylaxis. ARM A: Patients receive letermovir orally (PO) or intravenously (IV) over 60 minutes once daily (QD) starting on day +1 post-transplant for 14 weeks. Patients undergo collection of blood samples for CMV polymerase chain reaction (PCR) analysis weekly for 14 weeks, every 2 weeks until week 24, week 32, week 40 and week 52. ARM B (CLOSED TO ACCRUAL 09/29/2025): Patients undergo collection of blood samples for CMV PCR analysis weekly for 14 weeks, every 2 weeks until week 24, week 32, week 40 and week 52.