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

Not yet recruiting

• Conditions: CMV

• Registration Number: NCT06211543
• Lead Sponsor: Grupo Espanol de trasplantes hematopoyeticos y terapia celular

Brief Summary

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).

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 Timeline

• Status Verified: 2024-01
• Study First Submitted: 2024-01-09
• Study First Submitted QC: 2024-01-09
• Last Update Submitted: 2024-01-09
• Study First Posted: 2024-01-18
• Last Update Posted: 2024-01-18
• Study Start: 2024-03-30
• Primary Completion: 2025-09-30
• Study Completion: 2026-03-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
CMV DNAemia requiring preemptive treatment or CMV disease	Week 14 post-SCT	To determinate the incidence of csCMV infection through week 14 post-SCT.

Secondary Outcome Measures

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