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

NCT05711667 | Recruiting Phase 3 DMC FDA Drug

• 5 other identifiers: ACCL1932NCI-2022-10769COG-ACCL1932U24CA196173UG1CA189955
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 29

Brief Summary

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.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Detection of CMV DNAemia

  Up to week 14 post-transplant

• CMV-free survival

  Up to 24 weeks post-transplant

Other Outcomes (13)

• Clinically significant CMV infection in early follow up

  Up to 24 weeks post-transplant

• Clinically significant CMV infection in late follow up

  Up to 52 weeks post-transplant

• Overall survival (OS) in early follow up

  Up to 24 weeks post-transplant

Study Arms (2)

ARM A (Letermovir prophylaxis)

EXPERIMENTAL

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; Drug: Letermovir

Arm B (No prophylaxis)

ACTIVE COMPARATOR

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

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

ARM A (Letermovir prophylaxis); Arm B (No prophylaxis)

Letermovir DRUG

Given PO or IV

Also known as: 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, Prevymis

ARM A (Letermovir prophylaxis)

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \>= 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Oncology Group: lead

Study Sites (29)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

RECRUITING

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

RECRUITING

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

Children's Hospital New Orleans

New Orleans, Louisiana, 70118, United States

RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

RECRUITING

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

RECRUITING

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

ACTIVE NOT RECRUITING

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

RECRUITING

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

NOT YET RECRUITING

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Specimen Handling; letermovir

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Caitlin W Elgarten

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2023
• First Posted: February 3, 2023
• Study Start: July 11, 2024
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-01

Locations

US (29)