A Study of the Drug Letermovir as Prevention of Cytomegalovirus Infection After Stem Cell Transplant in Pediatric Patients
NCT ID: NCT05711667
Last Updated: 2025-11-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
105 participants
INTERVENTIONAL
2024-07-11
2029-06-30
Brief Summary
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Detailed Description
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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: Patients are randomized to 1 of 2 arms.
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: 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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
SINGLE
Study Groups
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ARM I (Letermovir prophylaxis)
Patients receive letermovir PO or IV over 60 minutes QD starting on day +1 post-transplant for 14 weeks. 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.
Biospecimen Collection
Undergo collection of blood samples
Letermovir
Given PO or IV
ARM II (No prophylaxis)
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.
Biospecimen Collection
Undergo collection of blood samples
Interventions
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Biospecimen Collection
Undergo collection of blood samples
Letermovir
Given PO or IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Weight must be \>= 18 kg. For patients \< 12 years of age and expected to receive cyclosporine, weight must be \>= 30kg
* 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)
* 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 \> 15 mL/min/1.73 m\^2 and not receiving dialysis
* Total bilirubin =\< 2.5 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
* Note: 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 eligibility
* 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
* Lovastatin
* Pitavastatin
* Rosuvastatin
* 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
2 Years
18 Years
ALL
No
Sponsors
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Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Caitlin W Elgarten
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Children's Hospital New Orleans
New Orleans, Louisiana, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Children's Hospital of Michigan
Detroit, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, United States
Medical City Dallas Hospital
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Countries
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Other Identifiers
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NCI-2022-10769
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACCL1932
Identifier Type: OTHER
Identifier Source: secondary_id
COG-ACCL1932
Identifier Type: OTHER
Identifier Source: secondary_id
ACCL1932
Identifier Type: OTHER
Identifier Source: secondary_id
ACCL1932
Identifier Type: -
Identifier Source: org_study_id