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

Letermovir Prophylaxis for Cytomegalovirus in Pediatric Hematopoietic Cell Transplantation

This phase III single arm trial determines whether taking prophylactic letermovir will reduce the likelihood of infection with cytomegalovirus (CMV) in children and adolescents after stem cell transplant compared to estimated rate of infection without prophylaxis. 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.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Letermovir

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Children's Hospital of Alabama
      • Principal Investigator: Joseph H. Chewning
      • Contact: Site Public Contact; Phone Number: 205-638-9285; Email: oncologyresearch@peds.uab.edu
  • California
    • Oakland, California, United States, 94609
      • Recruiting
      • UCSF Benioff Children's Hospital Oakland
      • Principal Investigator: Jennifer G. Michlitsch
      • Contact: Site Public Contact; Phone Number: 510-428-3264; Email: PedOncRschOAK@ucsf.edu
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Medical Center-Mission Bay
      • Contact: Site Public Contact; Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu
      • Principal Investigator: Lena E. Winestone
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Site Public Contact; Phone Number: 303-764-5056; Email: josh.b.gordon@nsmtp.kp.org
      • Principal Investigator: Sanam Shahid
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Recruiting
      • Alfred I duPont Hospital for Children
      • Contact: Site Public Contact; Phone Number: 302-651-5572; Email: Allison.bruce@nemours.org
      • Principal Investigator: Sridhi Patel
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Recruiting
      • Nemours Children's Clinic-Jacksonville
      • Contact: Site Public Contact; Phone Number: 302-651-5572; Email: Allison.bruce@nemours.org
      • Principal Investigator: Sridhi Patel
    • Miami, Florida, United States, 33155
      • Recruiting
      • Nicklaus Children's Hospital
      • Contact: Site Public Contact; Phone Number: 888-624-2778
      • Principal Investigator: Ossama M. Maher
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Recruiting
      • Kapiolani Medical Center for Women and Children
      • Contact: Site Public Contact; Phone Number: 808-983-6090
      • Principal Investigator: Wade T. Kyono
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Hospital for Children
      • Principal Investigator: April Rahrig
      • Contact: Site Public Contact; Phone Number: 800-248-1199
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa/Holden Comprehensive Cancer Center
      • Contact: Site Public Contact; Phone Number: 800-237-1225
      • Principal Investigator: Andrew P. Groves
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Children's Hospital
      • Contact: Site Public Contact; Phone Number: 502-629-5500; Email: CancerResource@nortonhealthcare.org
      • Principal Investigator: Michael J. Ferguson
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Recruiting
      • Children's Hospital New Orleans
      • Principal Investigator: Maria C. Velez-Yanguas
      • Contact: Site Public Contact; Phone Number: 504-894-5377
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Principal Investigator: Heather J. Symons
      • Contact: Site Public Contact; Phone Number: 410-955-8804; Email: jhcccro@jhmi.edu
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Children's Hospital of Michigan
      • Contact: Site Public Contact; Email: helpdesk@childrensoncologygroup.org
      • Principal Investigator: Erin Goode
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
      • Contact: Site Public Contact; Phone Number: 616-391-1230; Email: crcwm-regulatory@crcwm.org
      • Principal Investigator: Kathleen Y. Butler
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Children's Mercy Hospitals and Clinics
      • Contact: Site Public Contact; Phone Number: 816-302-6808; Email: COGResearchGroup@cmh.edu
      • Principal Investigator: Lauren C. Wilson
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Principal Investigator: Shalini Shenoy
      • Contact: Site Public Contact; Phone Number: 800-600-3606; Email: info@siteman.wustl.edu
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma Health Sciences Center
      • Contact: Site Public Contact; Phone Number: 405-271-8777; Email: ou-clinical-trials@ouhsc.edu
      • Principal Investigator: Rene Y. McNall-Knapp
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Site Public Contact; Phone Number: 267-425-5544; Email: CancerTrials@email.chop.edu
      • Principal Investigator: Caitlin W. Elgarten
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Active, not recruiting
      • Saint Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University/Ingram Cancer Center
      • Principal Investigator: Carrie L. Kitko
      • Contact: Site Public Contact; Phone Number: 800-811-8480
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • The Children's Hospital at TriStar Centennial
      • Contact: Site Public Contact; Phone Number: 615-342-1919
      • Principal Investigator: Clinton M. Carroll
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern/Simmons Cancer Center-Dallas
      • Contact: Site Public Contact; Phone Number: 214-648-7097; Email: canceranswerline@UTSouthwestern.edu
      • Principal Investigator: Victor M. Aquino
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Medical City Dallas Hospital
      • Contact: Site Public Contact; Phone Number: 972-566-5588
      • Principal Investigator: Maurizio L. Ghisoli
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Principal Investigator: Anil George
      • Contact: Site Public Contact; Phone Number: 713-798-1354; Email: burton@bcm.edu
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Methodist Children's Hospital of South Texas
      • Contact: Site Public Contact; Phone Number: 210-575-6240; Email: Vinod.GidvaniDiaz@hcahealthcare.com
      • Principal Investigator: Jose M. Esquilin
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Recruiting
      • Primary Children's Hospital
      • Contact: Site Public Contact; Phone Number: 801-585-5270
      • Principal Investigator: Soohee Cho
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Not yet recruiting
      • VCU Massey Comprehensive Cancer Center
      • Principal Investigator: Elizabeth Krieger
      • Contact: Site Public Contact; Phone Number: 804-628-6430; Email: CTOclinops@vcu.edu
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin Carbone Cancer Center - University Hospital
      • Contact: Site Public Contact; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu
      • Principal Investigator: Christian M. Capitini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM A (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.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Letermovir; Given PO or IV; Other Names: Prevymis; 2-((4S)-8-Fluoro-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)-4H-quinazolin-4-yl)acetic Acid; AIC246; MK-8228
Active Comparator: Arm B (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. (CLOSED TO ACCURAL 09/29/2025)	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically significant cytomegalovirus (CMV) infection	Clinically significant CMV is defined as the first of (1) initiation of anti-CMV preemptive therapy for documented CMV DNAemia or (2) onset of CMV end-organ disease. Will estimate the cumulative incidence of clinically significant CMV at 14-weeks post-transplant and will report the corresponding 95% confidence interval.	Up to week 14 post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of CMV DNAemia	Will estimate the cumulative incidence of CMV DNAemia at 14-weeks post-transplant by study arm and will report the corresponding 95% confidence intervals.	Up to week 14 post-transplant
CMV-free survival	Will estimate the cumulative incidence of the occurrence of CMV DNAemia or death by week 24 post-transplant by study arm and will report the corresponding 95% confidence intervals.	Up to 24 weeks post-transplant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically significant CMV infection in early follow up	Clinically significant CMV is defined as the first of (1) initiation of anti-CMV preemptive therapy for documented CMV DNAemia or (2) onset of CMV end-organ disease. Will estimate the cumulative incidence of clinically significant CMV at 24-weeks post-transplant and will report the corresponding 95% confidence interval.	Up to 24 weeks post-transplant
Clinically significant CMV infection in late follow up	Clinically significant CMV is defined as the first of (1) initiation of anti-CMV preemptive therapy for documented CMV DNAemia or (2) onset of CMV end-organ disease. Will estimate the cumulative incidence of clinically significant CMV at 52-weeks post-transplant and will report the corresponding 95% confidence interval.	Up to 52 weeks post-transplant
Overall survival (OS) in early follow up	The Kaplan-Meier method will be used to estimate the 24-week OS probability, as defined by time from transplant until death. The corresponding 95% confidence interval will be reported.	Up to 24 weeks post-transplant
Overall survival (OS) in late follow up	The Kaplan-Meier method will be used to estimate the 52-week OS probability, as defined by time from transplant until death. The corresponding 95% confidence interval will be reported.	Up to 52 weeks post-transplant
Neutrophil engraftment	Engraftment is defined as the first three days of neutrophil count values above 500 cells/μL. Will estimate the cumulative incidence of neutrophil engraftment at 60-days post-transplant and will report the corresponding 95% confidence interval.	Up to 60 days post-transplant
Incidence of neutropenia	Neutropenia will be defined as an absolute neutrophil count < 500 cells/uL. Will estimate the median number of weeks of neutropenia post-transplant.	Up to 14 weeks post-transplant
Incidence of acute kidney injury	Acute kidney injury will be defined as grade 3 or higher creatinine elevation using the common terminology criteria for adverse events (CTCAE) v5 definitions. Will estimate the cumulative incidence of acute kidney injury at 52-weeks post-transplant and will report the corresponding 95% confidence interval.	Up to 52 weeks post-transplant
Incidence of chronic kidney disease	Chronic kidney disease will be defined as grade 2 or higher using the CTCAE v5 definitions. Will estimate the cumulative incidence of chronic kidney disease at 52-weeks post-transplant and will report the corresponding 95% confidence interval.	Up to 52 weeks post-transplant
Number of inpatient hospital days	Will report the median number of inpatient hospital days post-transplant.	Up to 14 weeks post-transplant
Number of inpatient hospital days	Will report the median number of inpatient hospital days post-transplant.	Up to one-year post-transplant
Incidence of resistance to antiviral medications	Will estimate the cumulative incidence of resistance to antiviral medications among the patients who develop clinically significant CMV infection. This analysis will be restricted to patients with viral loads > 1000 IU/mL.	Up to 14 weeks post-transplant
CD4+ lymphocyte count	Will report the median CD4+ lymphocyte count.	At 14, 24, and 52 weeks post-transplant
CD8+ lymphocyte count	Will report the median CD8+ lymphocyte count.	At 14, 24, and 52 weeks post-transplant

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Investigators: Principal Investigator: Caitlin W Elgarten, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2024
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; letermovir
• Other Study ID Numbers: ACCL1932 (Other Identifier: CTEP); UG1CA189955 (U.S. NIH Grant/Contract); U24CA196173 (U.S. NIH Grant/Contract); NCI-2022-10769 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); COG-ACCL1932 (Other Identifier: DCP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes