A Study of the Drug Letermovir (LTV) as Prevention for Recurrent of Cytomegalovirus (CMV) Infection

An Open-label, Single-arm Study of Letermovir (LTV) for Prevention of Recurrent CMV Infection in High-risk Hematopoietic Cell Transplant (HCT) Recipients

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04017962

Enrollment

102

Registered

2019-07-12

Start date

2019-07-19

Completion date

2025-07-29

Last updated

2025-08-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

CMV, CMV Infection, Hematopoietic Cell Transplant

Keywords

HCT, CMV infection, Letermovir, LTV, Memorial Sloan Kettering Cancer Center, 19-174

Brief summary

The purpose of this study is to determine of letermovir (LTC) is effective at preventing Cytomegalovirus (CMV) infection from returning in people who have already had CMV infection after a bone marrow transplant.

Interventions

DRUGLetermovir Pill

Patients enrolled on the study will receive oral LTV 480 mg daily (240 mg daily for patients receiving cyclosporine A). The maximum duration of LTV administration will be 14 weeks. Patients receiving oral medication will be administered a pill diary for drug compliance purposes. This will be administered and reconciled in clinic.

OTHERblood draw

Collection of blood samples for CMV-CMI analysis via CMV immunity T cell panel assay on day 100. Patients with negative CMI on day 100 undergo collection of blood samples for retesting on day 180.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age \>/= 12 years (any weight) * Have received allogenic HCT * Have received preemptive therapy for clinically significant CMV infection post-HCT and have completed preemptive therapy no longer than 7 days prior to enrollment. Preemptive treatment includes ganciclovir, valganciclovir, foscarnet or cidofovir. Clinically significant CMV infection is defined as CMV viremia requiring preemptive therapy or CMV EOD. Patients who have received LTV prophylaxis prior to onset of clinically significant CMV infection prior to enrollment (see also

Exclusion criteria

below). * Have one or more risk factors for recurrent CMV infection: 1. Human leukocyte antigen (HLA) mismatch * HLA-related (sibling) donor with at least one mismatch at the HLA-A, -B or -DR gene loci * Haploidentical donor * Unrelated donor with at least one mismatch at the HLA-A, -B, -C or -DRC1gene loci, or * Cord blood as stem cell source 2. Acute or chronic GVHD requiring either topical steroids for gastrointestinal GVHD and/or systemic steroid treatment (\>/= 1mg/kg/day of prednisone or equivalent dose of another corticosteroid) within 14 days prior to enrollment 3. T-cell-depleted allograft ex-vivo or in-vivo T-cell depleting agents including but not limited to ATG, alemtuzimab and post HCT cyclophosphamide. * For adult patients, able to provide written consent and complete the informed consent. For patients under 18 years, the patient's parent(s) or legal guardian(s) must provide informed consent and the patient must provide written assent to participation in the study. * Willing and able to comply with trial instructions and requirements * Male and female patients of childbearing potential must be willing to use a highly effective method of contraception for the course of the study. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient. Subject eligibility criteria for the observational cohort: * Age 18 years or older * First allogenic peripheral blood or marrow HCT * LTV prophylaxis starting \<30 days post HCT and given for at least 6 weeks

Design outcomes

Primary

Measure	Time frame	Description
Clinically Significant CMV Viremia for Hematopoietic Cell Transplantation/HCT Participants in the Interventional Cohort Only	14 weeks	Clinically significant CMV viremia defined as: Any level CMV DNAemia requiring preemptive treatment per Institutional standard of care at each participating Institution.

Secondary

Measure	Time frame	Description
Number of Participants With Breakthrough Clinically Significant CMV Viremia With Emergence of Letermovir-resistant CMV Virus for Hematopoietic Cell Transplantation/HCT Participants in the Interventional Cohort Only	14 weeks	Emergence of Letermovir-resistant CMV Virus in Patients with breakthrough clinically significant CMV viremia.
CMV End Organ Disease for Hematopoietic Cell Transplantation/HCT Participants in the Interventional Cohort Only	14 weeks	—
CMV Related Death for Hematopoietic Cell Transplantation/HCT Participants in the Interventional Cohort Only	14 weeks	—
Adverse Events at Least Possibly Related to Letermovir by the Treating Physician for Hematopoietic Cell Transplantation/HCT Participants in the Interventional Cohort Only	14 weeks	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
Hematopoietic Cell Transplantation/HCT INTERVENTIONAL COHORT: Patients receive letermovir PO QD (or IV over 1 hour for patients unable to receive PO) for 14 weeks in the absence of disease progression or unacceptable toxicity. Participants will be hematopoietic cell transplantation (HCT) recipients with a history of CMV infection.	36
Observational Cohort Participants will be hematopoietic cell transplantation (HCT) recipients with a history of CMV infection. Patients undergo collection of blood samples for CMV-CMI analysis via CMV immunity T cell panel assay on day 100. Patients with negative CMI on day 100 undergo collection of blood samples for retesting on day 180.	66
Total	102

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	2
Overall Study	Discontinued LTV	5
Overall Study	Lost to Follow-up	2
Overall Study	Physician Decision	1

Baseline characteristics

Characteristic	Hematopoietic Cell Transplantation/HCT	Total	Observational Cohort
Age, Continuous	59 years	60 years	63 years
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants	14 Participants	10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants	88 Participants	56 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	9 Participants	16 Participants	7 Participants
Race (NIH/OMB) Black or African American	4 Participants	7 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	6 Participants	5 Participants
Race (NIH/OMB) White	22 Participants	72 Participants	50 Participants
Region of Enrollment India	1 Participants	1 Participants	0 Participants
Region of Enrollment United States	35 Participants	101 Participants	66 Participants
Sex: Female, Male Female	18 Participants	47 Participants	29 Participants
Sex: Female, Male Male	18 Participants	55 Participants	37 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 36	0 / 66
other Total, other adverse events	0 / 36	0 / 66
serious Total, serious adverse events	2 / 36	0 / 66

Outcome results

Primary

Clinically Significant CMV Viremia for Hematopoietic Cell Transplantation/HCT Participants in the Interventional Cohort Only

Clinically significant CMV viremia defined as: Any level CMV DNAemia requiring preemptive treatment per Institutional standard of care at each participating Institution.

Time frame: 14 weeks