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Letermovir to prevent cytomegalovirus after pediatric stem cell transplant

Letermovir Prophylaxis for Cytomegalovirus in Pediatric Hematopoietic Cell Transplantation

PHASE3 · Children's Oncology Group · NCT05711667

This study will try giving letermovir to CMV-positive children and adolescents receiving allogeneic stem cell transplants to see if it lowers CMV infections after transplant compared with the expected rate without prophylaxis.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment105 (estimated)
Ages2 Years to 18 Years
SexAll
SponsorChildren's Oncology Group (network)
Locations29 sites (Birmingham, Alabama and 28 other locations)
Trial IDNCT05711667 on ClinicalTrials.gov

What this trial studies

This phase 3, single-arm trial gives prophylactic letermovir to CMV IgG–positive children and adolescents (ages 2 to under 18 years) undergoing allogeneic hematopoietic cell transplant to determine the incidence of clinically significant CMV infection through about 14 weeks (~100 days) post-transplant. The primary endpoint is clinically significant CMV infection through Week 14 and the key secondary endpoint is CMV-free survival through 24 weeks (~6 months). Exploratory outcomes include CMV incidence through 24 and 52 weeks, overall survival, time to engraftment, selected kidney and neutropenia-related adverse events, antiviral resistance patterns, and measures of immune reconstitution. Participants must weigh at least 6 kg and be treated at participating centers able to perform timely plasma CMV PCR monitoring.

Who should consider this trial

Good fit: Ideal candidates are CMV IgG–positive children and adolescents aged 2 to under 18 years who are planning an allogeneic hematopoietic cell transplant, weigh >= 6 kg, and can have timely plasma CMV PCR testing per protocol.

Not a fit: CMV-seronegative patients, children under 2 years or adults, patients already with detectable CMV viremia at enrollment, or those unable to obtain rapid CMV PCR results are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, letermovir prophylaxis could reduce the risk of CMV infection and its complications after pediatric allogeneic stem cell transplant.

How similar studies have performed: Adult phase 3 trials have shown that letermovir prophylaxis significantly reduces CMV infection after hematopoietic cell transplant, while pediatric data remain limited and less established.

Eligibility criteria

Show full inclusion / exclusion criteria 
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)
  * Foscarnet
  * 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:

    * Pimozide
    * Ergot alkaloids
  * Contraindicated medications for patients planned to receive cyclosporine:

    * Bosentan
    * 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

Where this trial is running

Birmingham, Alabama and 28 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.