Letermovir Prophylaxis for CMV Infection in Haplo-HSCT Recipients: Single-center Data in China

February 17, 2025 updated by: The First Affiliated Hospital of Soochow University

Letermovir Prophylaxis for Cytomegalovirus Infection in Haploidentical Allogeneic Hematopoietic Cell Transplant Recipients: Single-center Real-world Data in China

In the 30 years of fighting CMV infection, the mortality rate among HSCT patients has significantly reduced. Now, the focus is on improving the prognosis of HSCT patients and preventing CMV infection. The emergence of letermovir has provided a new opportunity in this regard. Letermovir, the only drug approved for CMV infection prevention in HSCT patients, works by inhibiting the CMV DNA terminase complex. Phase III studies have shown that letermovir significantly reduces CMV infection and all-cause mortality after HSCT, without increasing myelosuppression or nephrotoxicity. Real-world studies have further confirmed its efficacy in reducing CMV infection rates and antiviral use. Letermovir's global success has not yet been fully realized in China, where it is still in its early stages of use.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Letermovir achieved excellent therapeutic outcomes globally but is still developing in China. It received an implied license for clinical trials in June 2020, followed by marketing applications in November 2020. In December 2021, it was approved by the China National Medical Products Administration (NMPA) for preventing CMV infection and disease in CMV seropositive adult recipients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir's commercial launch in China is expected in August 2022. Given that over 90% of the Chinese population is CMV seropositive, determining whether CMV prevention is necessary based solely on serology is insufficient. The growing use of haploidentical stem cell transplantation (haplo-SCT) in China, particularly using the Beijing protocol for GVHD prevention, increases CMV risk. However, limited data exists on the efficacy of CMV prophylaxis for haplo-SCT patients in China. A real-life study assessing the efficacy, resistance, and tolerability of letermovir in this patient group is essential to guide CMV management strategies, particularly for high-risk CMV R+ haploidentical transplant recipients. This prospective study aims to evaluate letermovir's real-life impact on efficacy, resistance, tolerability, and CMV-related morbidity and mortality in China.

Study Type

Observational

Enrollment (Actual)

200

Contacts and Locations

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

Study Locations

  • China
    • Jiangsu
      • Suzhou, Jiangsu, China
        • The First Affiliated Hospital of Soochow University

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

The study consists 200 cases CMV-R+ adult (>18 years) recipients of haplo-HCT. All patients will receive letermovir prophylaxis.

Description

Inclusion Criteria:

  • Haplo-SCT candidate (adult) who has decided to primary transplant and is willing to participate in the study.
  • The haplo-SCT candidate (adult) should be CMV seropositive recipients.

Exclusion Criteria:

  • CMV-seronegative patient receiving a negative CMV donor graft.
  • Patients having active CMV DNAemia at the time of letermovir initiation.
  • Patient having signed the informed consent but not grafted.
  • Patient recruited in a clinical study on an anti-CMV trial.

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
200 haplo-HSCT recipients who are CMV seropositive

The study consists 200 cases CMV-R+ adult (>18 years) recipients of haplo-HCT. All patients will receive letermovir prophylaxis. Consider a simple interim analysis of the experimental group could be arranged after 150 patients are enrolled if necessary.

Supportive care is provided by institutional standards of care (e.g., acyclovir for herpes simplex virus and varicella zoster virus prevention).

Letermovir prophylaxis is started on day 0 or no longer than 28 days after transplantation. During the study period, letermovir 480 mg PO/IV once daily (or 240 mg per day in patients taking cyclosporine) was administered from day 0 to day +100 post-HCT.

CMV monitoring and preemptive therapy were performed according to local protocol. Plasma CMV viral load (VL) is monitored by quantitative CMV PCR, starting on day +7 and continued weekly until week 6, then every 2-4 weeks for months until week 24.
Drug: Letermovir
Letermovir has achieved excellent therapeutic benefits globally but is still in its infancy in China. Letermovir obtained an implied license for a clinical trial in June 2020, and in November 2020, Letermovir submitted and accepted four new drug marketing applications in China, including injection and tablet formulations. On December 31, 2021, the China National Medical Products Administration (NMPA) approved letermovir for cytomegalovirus (CMV) seropositive adult recipients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) [R+] prevention of cytomegalovirus infection and cytomegalovirus disease. The commercial launch of letermovir is estimated to be in August 2022.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of clinically significant CMV infection
Time Frame: at Week 14 following haplo-SCT
Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease using classificatory criteria published by the Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. CMV DNA threshold for initiation of preemptive therapy at our center is viral load >500 copies/mL or above on two consecutive tests.
at Week 14 following haplo-SCT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of clinically significant CMV infection
Time Frame: through Week 24 following haplo-SCT
Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease using classificatory criteria published by the Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. CMV DNA threshold for initiation of preemptive therapy at our center is viral load >500 copies/mL or above on two consecutive tests.
through Week 24 following haplo-SCT
Incidence of CMV DNAemia and CMV disease
Time Frame: through Week 14 and Week 24 following haplo-SCT
CMV DNAemia refers to the presence of CMV DNA in the blood. CMV disease refers to the organ dysfunction caused by an active CMV infection, such as the lungs, liver, and retina.
through Week 14 and Week 24 following haplo-SCT
Incidence of the resistant or refractory CMV infection
Time Frame: through Week 24 following haplo-SCT
Resistant or refractory CMV infection occurs if CMV levels rise by 1 log after 2 weeks of treatment or remain positive after 4 weeks.
through Week 24 following haplo-SCT
Incidence of serious adverse event leading to interruption of treatment
Time Frame: through Week 24 following haplo-SCT
Serious adverse events refers to events that require stopping the treatment to ensure patient safety.
through Week 24 following haplo-SCT
Incidence of CMV-related disease mortality
Time Frame: through Week 24 following haplo-SCT
Death resulting directly or indirectly from complications of a CMV infection, often involving severe organ damage in the lungs, liver, or other organs.
through Week 24 following haplo-SCT
Incidence of all-cause mortality and non-relapse mortality
Time Frame: through Week 24 following haplo-SCT
All-cause mortality refers to deaths from any cause, while non-relapse mortality refers to deaths caused by factors other than the recurrence or relapse of the original disease or condition.
through Week 24 following haplo-SCT
Incidence of CMV-associated morbidity
Time Frame: through Week 24 following haplo-SCT
CMV-associated morbidity refers to organ damage, delay engraftment, acute or chronic GVHD occurrence, or other infectious diseases caused by CMV.
through Week 24 following haplo-SCT
Incidence of rehospitalization
Time Frame: through Week 14, Week 24 following haplo-HSCT
The frequency or rate at which patients are readmitted to the hospital within a specified period following their discharge.
through Week 14, Week 24 following haplo-HSCT

Collaborators and Investigators

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

Sponsor

The First Affiliated Hospital of Soochow University

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Chair: Xiaojin Wu, Prof., The First Affiliated Hospital of Soochow University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

April 1, 2023

Primary Completion (Actual)

January 10, 2025

Study Completion (Actual)

January 10, 2025

Study Registration Dates

First Submitted

March 16, 2023

First Submitted That Met QC Criteria

March 16, 2023

First Posted (Actual)

March 29, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 17, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SOOCHOW-WXJ-2022-366

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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