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

Inclusion criteria

• \>= 2 years and \< 18 years at the time of enrollment
• Weight must be \>= 6 kg at the time of enrollment
• Planned 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)
• Note: If a patient has hypogammaglobulinemia but has previously been documented as CMV sero-positive, that is acceptable for study inclusion. For all patients already confirmed to be CMV IgG seropositive, repeat testing is not required within 7 days prior to enrollment. However, the laboratory data determining eligibility must be available in the patient's medical/research record for verification
• 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 period
• Reminder: 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 regimen
• Patient must have a performance status corresponding to Lansky/Karnofsky scores \> 50
• Note: 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.asp
• Estimated glomerular filtration rate \> 10 mL/min/1.73 m\^2 and not receiving dialysis
• Direct bilirubin =\< 2 mg/dL and serum glutamate-pyruvate transaminase (SPGT) (alanine transaminase \[ALT\]) =\<10 x upper limit of normal (ULN) for age
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L

Exclusion criteria

• Expected inability to tolerate oral formulation of letermovir
• Hypersensitivity to letermovir or any component of the formulation
• History of CMV end organ disease within 6 months (180 days) prior to enrollment
• Note: CMV end organ disease based on proposed definitions by Ljungman et al. and inclusive of proven, probable or possible disease
• Receipt of prior allogeneic HCT within one year of study enrollment
• Planned 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)
• Ganciclovir
• Valganciclovir
• CMV-directed cytotoxic T lymphocytes
• Planned receipt of the following contraindicated medications during the study treatment period; contraindicated medications must be discontinued at least 14 days prior to Day +1
• Contraindicated medications for all patients:
• Ergot alkaloids
• Contraindicated medications for patients planned to receive cyclosporine:
• Pitavastatin
• Simvastatin
• Female 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 potential
• Lactating females who plan to breastfeed their infants
• Sexually 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 consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met