Letermovir Prophylaxis in Children With EBV-Positive T/NK-Cell Lymphoproliferative Disease and Refractory/Relapsed EBV-Associated Hemophagocytic Lymphohistiocytosis

March 18, 2026 updated by: Jun Yang, Beijing Children's Hospital

Impact of Letermovir Prophylaxis on Viral Infections After Allogeneic Hematopoietic Stem Cell Transplantation in Children With EBV-Positive T/NK-Cell Lymphoproliferative Disease and Refractory/Relapsed EBV-Associated Hemophagocytic Lymphohistiocytosis

This study investigates the impact of letermovir prophylaxis on viral infections (including CMV, EBV, BKV, HHV-6/7, RSV, ADV, HSV, etc.) following allogeneic hematopoietic stem cell transplantation in pediatric patients with EBV-associated T/NK-cell lymphoproliferative diseases and refractory/relapsed EBV-related hemophagocytic lymphohistiocytosis. Additionally, we examine its effects on other transplantation complications, including engraftment failure, graft-versus-host disease (GvHD), disease relapse, thrombotic microangiopathy (TMA), overall survival (OS), post-transplant lymphoproliferative disorder (PTLD) incidence, and immune reconstitution.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100032
        • Recruiting
        • Beijing Children's Hospital, Capital Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosed with EBV-positive T/NK lymphoproliferative disease (EBV-T/NK LPD) according to ICC 2022 criteria, or diagnosed with refractory/relapsed EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) according to the 2004-HLH diagnostic criteria;
  • Undergoing first allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the study center;
  • Age < 18 years;
  • CMV seropositive (IgG+) prior to transplantation;
  • Presence of at least one high-risk factor for CMV infection: haploidentical transplantation, HLA-mismatched transplantation, receipt of ATG (including ATLG/ALG) in conditioning, sustained corticosteroid use post-conditioning, donor/recipient CMV serostatus mismatch, or positive NGS result pre-transplant.

Exclusion Criteria:

  • History of CMV end-organ disease within 6 months prior to enrollment;
  • Severe hepatic dysfunction (defined as Child-Pugh Class C);
  • End-stage renal impairment with creatinine clearance < 10 mL/min (calculated by Cockcroft-Gault equation);
  • Prior allogeneic hematopoietic stem cell transplantation;
  • Expected survival ≤ 3 months;
  • Received radiation therapy during conditioning;
  • Initiation of letermovir prophylaxis after day 28 post-transplant;
  • Letermovir dosage or administration not in accordance with the prescribing information;
  • Lack of signed informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Children with Letermovir for Cytomegalovirus prophylaxis after HSCT
Drug: Letermovir

Arm 1 (Letermovir Prophylaxis): Pediatric patients receive oral letermovir once daily from day 0 to day 100 post-transplant. Prophylaxis may be extended to day 200 if high-risk factors persist (steroid use, poor immune reconstitution). Dosing: 480mg (≥30kg), 240mg (15-30kg), 120mg (7.5-15kg), 80mg (6-7.5kg); halved if co-administered with cyclosporine.

Arm 2 (Control): Historical control cohort (2018-2023) receiving no routine CMV prophylaxis; preemptive therapy with ganciclovir/foscarnet initiated only when plasma PCR exceeds threshold.
No Intervention: Children with preemptive therapy, without Letermovir for Cytomegalovirus prophylaxis after HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Clinically Significant CMV Infection (cs-CMVi) and EBV Infection (cs-EBVi)
Time Frame: Up to 180 days and 360 days post-transplant
To evaluate the incidence of clinically significant CMV and EBV infections in pediatric patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with or without letermovir prophylaxis.
Up to 180 days and 360 days post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Other Viral Infections and Transplant-Related Complications
Time Frame: Up to 100, 180, 270, and 360 days post-transplant
To assess the incidence of other viral infections (e.g., BKV, HHV-6/7, RSV, ADV, HSV), graft-versus-host disease (GvHD), post-transplant lymphoproliferative disorder (PTLD), thrombotic microangiopathy (TMA), graft failure, relapse, overall survival (OS), and immune reconstitution (T/B/NK cell counts and function).
Up to 100, 180, 270, and 360 days post-transplant

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of Letermovir in Pediatric allo-HSCT Recipients
Time Frame: From initiation of letermovir (Day 0-28 post-transplant) until 30 days after discontinuation (up to approximately 360 days post-transplant)
To monitor adverse events (AEs) and serious adverse events (SAEs) related to letermovir prophylaxis, including gastrointestinal symptoms, liver function abnormalities, cardiac events, and other treatment-emergent AEs.
From initiation of letermovir (Day 0-28 post-transplant) until 30 days after discontinuation (up to approximately 360 days post-transplant)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

March 18, 2026

First Submitted That Met QC Criteria

March 18, 2026

First Posted (Actual)

March 23, 2026

Study Record Updates

Last Update Posted (Actual)

March 23, 2026

Last Update Submitted That Met QC Criteria

March 18, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • [2025]-Y-242-D

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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