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

This phase III trial determines whether taking prophylactic letermovir will reduce the likelihood of infection with cytomegalovirus (CMV) in children and adolescents after stem cell transplant. The treatments used to prepare for HCT reduce the body's natural infection-fighting ability and increase the likelihood of an infection with a virus called cytomegalovirus. "Prophylaxis" means to take a drug to prevent a disease or side effect. Letermovir is an antiviral drug that stops cytomegalovirus from multiplying and may prevent cytomegalovirus infection and make the disease less severe.

Inclusion Criteria:>= 2 years and < 18 years at the time of enrollmentWeight must be >= 18 kg. For patients < 12 years of age and expected to receive cyclosporine, weight must be >= 30kgPlanned allogeneic HCT (bone marrow, peripheral blood stem cell, or cord blood transplant)Patient must be CMV sero-positive (i.e., recipient CMV immunoglobulin G positive)Patient is eligible for entry only if it is feasible for plasma CMV PCR testing to be sent and resulted within the protocol mandated time periodReminder: To limit the likelihood of positive plasma CMV PCR post-enrollment and prior to start of study treatment period, it is recommended that patient enrollment proceed after patients start their transplant preparative regimenPatient must have a performance status corresponding to Lansky/Karnofsky scores > 50Note: Use Lansky for patients =< 16 years of age and Karnofsky for patients > 16 years of age. For further reference, see performance status scales scoring under the standard sections for protocols among protocol reference materials provided on the Children's Oncology Group (COG) member website: https://members.childrensoncologygroup.org/prot/reference_materials.aspEstimated glomerular filtration rate > 15 mL/min/1.73 m^2 and not receiving dialysisTotal bilirubin =< 2.5 mg/dL and serum glutamate-pyruvate transaminase (SPGT) (alanine transaminase [ALT]) =<10 x upper limit of normal (ULN) for ageNote: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/LExclusion Criteria:Expected inability to tolerate oral formulation (e.g., unable swallow whole tablets) of letermovirNote: Determination of ability to tolerate the oral formulation will be based on a self-assessment or caregiver assessment; eligible subjects and their caregiver will be shown a life size picture of a tablet (or actual tablet) and confirm ability to swallow whole tablet in order to meet study eligibilityHypersensitivity to letermovir or any component of the formulationHistory of CMV end organ disease within 6 months (180 days) prior to enrollmentNote: CMV end organ disease based on proposed definitions by Ljungman et al. and inclusive of proven, probable or possible diseaseReceipt of prior allogeneic HCT within one year of study enrollmentPlanned prophylactic administration of other anti-CMV medications or cellular products during the study, including:High dose acyclovir (defined as doses >= 1500 mg/m^2 IV or >= 3200 mg oral (patients >= 40 kg) or >= 2400 mg/m^2 (patients < 40 kg) per day)High dose valacyclovir (defined as doses >= 3000 mg/day in patients > 20 kg)FoscarnetGanciclovirValganciclovirCMV-directed cytotoxic T lymphocytesPlanned receipt of the following contraindicated medications during the study treatment period; contraindicated medications must be discontinued at least 14 days prior to Day +1Contraindicated medications for all patients:PimozideErgot alkaloidsContraindicated medications for patients planned to receive cyclosporine:BosentanLovastatinPitavastatinRosuvastatinSimvastatinFemale patients who are pregnant since fetal toxicities and teratogenic effects have been noted in certain animal reproduction studies with letermovir. A pregnancy test is required for female patients of childbearing potentialLactating females who plan to breastfeed their infantsSexually active female patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their letermovir treatment and through at least 4 weeks after the last dose of letermovir.Note: No contraception measures are needed specifically during letermovir treatment for male trial participants who have pregnant or non-pregnant female partner(s) of reproductive potential. Contraception measures may be required for other aspects of the HCT procedure.All patients and/or their parents or legal guardians must sign a written informed consentAll institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met