Letermovir (LMV) Prophylaxis in CMV-seronegative Allogeneic Stem Cell Transplant Recipients With CMV Seropositive Donors: an Exploratory Study From Spanish GETH/TC Centers

This is an observational cohort study. Two cohort will be enrolled:

LMV cohort: All patients included in in this study will receive LMV according to standard of care.

Historical cohort: an historical cohort will be included to compare the results of both groups (LMV vs historical cohort).

Study Overview

• Status: Not yet recruiting
• Conditions: CMV

Detailed Description

All patients will receive treatment wtith LMV according to standard of care.

Eligible patients will be enrolled in the study under the supervision of the investigator or designated sub-investigators. If possible, patients will receive treatment on an outpatient basis except for the hospitalization requirement established in the protocol.

Patients will receive oral or intravenous LMV (if available) at a dose of 480 mg/day. For patients receiving concomitant treatment with cyclosporine, the dose of LMV will be 240 mg/day. According to the standard of care, LMV will be administered daily until week 14 post-transplant for up to 8 weeks (~day 100) starting on day +1.

Patients could be discontinued earlier if, disease progression, patient withdrawal, loss to follow-up, end of study, or death.

After completion of the treatment period, an end-of-treatment visit will occur within 30 days of receipt of the last dose of study drug.

To compare the outcome of the LMV group, a historical cohort will be selected from the national CMV database (GETH-GRUCINI).

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Irene García Cadenas, MD; Phone Number: 934893000; Email: IGarciaCa@santpau.cat
• Study Contact Backup: Name: Jose Luis Piñana, MD; Email: jlpinana@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

CMV-seronegative Allogeneic Stem Cell Transplant Recipients with CMV seropositive donors

Description

Inclusion Criteria:

• Age ≥18 years
• First allogenic HCT
• Pre-HCT patient CMV negative IgG serology with CMV IgG positive donor serostatus
• Able to provide written consent and complete the informed consent
• Absence of CMV DNAemia requiring antiviral therapy within 5 days before initiation of LMV. Low levels CMVDNAemia before the inception of letermovir are allowed

Exclusion Criteria

• Active pre-emptive therapy for csCMV-I.
• Patients who have received LMV prophylaxis prior to enrollment
• Patients enrolled in a CMV pre-emptive therapy clinical trial
• Glomerular filtration rate (GFR) </=30 mL/min/1.73m^2 (equivalent to creatinine clearance </=10 mL/min)
• Severe hepatic function grade 3-4 CTAE at the time of study entry.
• Suspected or known hypersensitivity to active or inactive ingredients of LMV formulations
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to letermovir.
• Pregnancy or breastfeeding
• Plans to conceive or father children within the projected duration of the trial
• History of current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or would place the subject at undue risk as judged by the investigator, such that it is not in the best interest of the subject to participate in this study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
LMV cohort; Patients will receive oral or intravenous (if available ) LMV at a dose of 480mg/day. For patients receiving concomitant cyclosporine treatment, the LMV dose will be 240mg/day. LMV will be administered daily through week 14 after transplantation for up to 8 weeks (~Day 100) beginning
Historical cohort; An historical control cohort for comparison purposes will be used. Historical data will be obtained from a national CMV data base (GETH-GRUCINI), that includes stem cell transplant recipients from September 2014 to December 2022

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CMV DNAemia requiring preemptive treatment or CMV disease	To determinate the incidence of csCMV infection through week 14 post-SCT.	Week 14 post-SCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophile (>0,5x10e9/L) and platelets engraftment (>20 x10e9/L) by day +40 post-SCT.	Engraftment incidence and time to engraftment	Day +40 post-SCT
Neutrophile (>0,5x10e9/L) and platelets engraftment (>20 x10e9/L) by day +100 post-SCT.	Engraftment incidence and time to engraftment	Day +100 post-SCT
Death by any cause and death not related with disease relapse or progression	All-cause mortality week 14	Week 14 post-SCT
Death by any cause non related to relapse	Non-relapse Mortality (NRM)	Week 14 post-SCT
Death by any cause non related to relapse	Non-relapse Mortality (NRM)	Week 24 post-SCT
Time to onset of all-cause failure of prophylaxis against CMV infection during the 8 weeks of study-drug administration period (day +100 post-transplant)	To evaluate the time to onset of all-cause failure of prophylaxis against CMV infection during the 8 weeks of study-drug administration period (day +100 post-transplant)	Up to 8 weeks of study-drug administration period (day +100 post-transplant)
Duration of any CMV-antiviral treatment by day 180 post-SCT	To estimate the duration of CMV-antiviral treatments by day 180 post-SCT.	day 180 post-SCT
Incidence of blips, clinical and analytic characteristics.	To investigate the natural history of blips in the LMV primary prophylaxis (PP) clinical setting	180 days post-SCT
Incidence of untreated CMV DNAemia	Incidence of low levels of CMV DNAemia not requiring PET	180 days post-SCT
Adverse events according to the CTCAE, physical examination and regular laboratory tests	To evaluate LMV tolerance and safety	180 days post-SCT
Incidence of aGVHD within 120 days after HCT and its onset and severity	To evalute de incidence of aGVHD and clinical characteristics.	120 days post-SCT
Incidence of relapse within 180 days after HCT and its onset and severity	To evalute de incidence of relapse and clinical characteristics.	180 days post-SCT
Incidence of CMV DNAemia requiring PET within 100-180 days after HCT	To establish incidence of late (> d +100) clinically significant CMV DNAemia	From day 100 to day 180 after HCT
Incidence of non-CMV infections within 180 days after HCT and its onset and severity	To establish de incidence of non-CMV infections.	180 days post-SCT

Collaborators and Investigators

• Sponsor: Grupo Espanol de trasplantes hematopoyeticos y terapia celular

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Estimated): January 18, 2024

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: CMV; Allogeneic Stem Cell Transplant
• Other Study ID Numbers: GETH-LMV

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No