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

NCT07488728 | Recruiting

• 1 other identifier: [2025]-Y-242-D
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

EBV-associated T/NK-cell Lymphoproliferative Diseases; Letermovir; Refractory/Relapsed EBV-related Hemophagocytic Lymphohistiocytosis

Keywords

EBV; Letermovir; EBV-associated T/NK-cell lymphoproliferative diseases; refractory/relapsed EBV-related hemophagocytic lymphohistiocytosis

Outcome Measures

Primary Outcomes (1)

• Incidence of Clinically Significant CMV Infection (cs-CMVi) and EBV Infection (cs-EBVi)

  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 Outcomes (1)

• Incidence of Other Viral Infections and Transplant-Related Complications

  Up to 100, 180, 270, and 360 days post-transplant

Other Outcomes (1)

• Safety and Tolerability of Letermovir in Pediatric allo-HSCT Recipients

  From initiation of letermovir (Day 0-28 post-transplant) until 30 days after discontinuation (up to approximately 360 days post-transplant)

Study Arms (2)

Children with Letermovir for Cytomegalovirus prophylaxis after HSCT

EXPERIMENTAL

Drug: Letermovir

Children with preemptive therapy, without Letermovir for Cytomegalovirus prophylaxis after HSCT

NO INTERVENTION

Interventions

Letermovir DRUG

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.

Children with Letermovir for Cytomegalovirus prophylaxis after HSCT

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Children's Hospital: lead

Study Sites (1)

Beijing Children's Hospital, Capital Medical University

Beijing, Beijing Municipality, 100032, China

RECRUITING

MeSH Terms

Interventions

letermovir

Central Study Contacts

Jun Yang, Doctor

CONTACT

+86 13699293825; yangjundabby@outlook.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Beijing Children's Hospital

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 23, 2026
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

CN (1)