Clinical trial NCT06211543: Letermovir (LMV) Prophylaxis in CMV-seronegative Allogeneic Stem Cell Transplant Recipients With CMV Seropositive Donors: an Exploratory Study From Spanish GETH/TC Centers
Official title: Letermovir (LMV) Prophylaxis in CMV-seronegative Allogeneic Stem Cell Transplant Recipients With CMV Seropositive Donors: an Exploratory Study From Spanish GETH/TC Centers
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: CMV
Keywords: CMV
Allogeneic Stem Cell Transplant
Lead sponsor: Grupo Espanol de trasplantes hematopoyeticos y terapia celular
Sponsor class: OTHER
First posted: 2024-01-18
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: CMV-seronegative Allogeneic Stem Cell Transplant Recipients with CMV seropositive donors

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).

Eligibility criteria: 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

Primary outcomes:
measure: CMV DNAemia requiring preemptive treatment or CMV disease
timeFrame: Week 14 post-SCT
Secondary outcomes:
measure: Neutrophile (>0,5x10e9/L) and platelets engraftment (>20 x10e9/L) by day +40 post-SCT.
timeFrame: Day +40 post-SCT
measure: Neutrophile (>0,5x10e9/L) and platelets engraftment (>20 x10e9/L) by day +100 post-SCT.
timeFrame: Day +100 post-SCT
measure: Death by any cause and death not related with disease relapse or progression
timeFrame: Week 14 post-SCT
measure: Death by any cause non related to relapse
timeFrame: Week 14 post-SCT
measure: Death by any cause non related to relapse
timeFrame: Week 24 post-SCT
measure: 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)
timeFrame: Up to 8 weeks of study-drug administration period (day +100 post-transplant)
measure: Duration of any CMV-antiviral treatment by day 180 post-SCT
timeFrame: day 180 post-SCT
measure: Incidence of blips, clinical and analytic characteristics.
timeFrame: 180 days post-SCT
measure: Incidence of untreated CMV DNAemia
timeFrame: 180 days post-SCT
measure: Adverse events according to the CTCAE, physical examination and regular laboratory tests
timeFrame: 180 days post-SCT
measure: Incidence of aGVHD within 120 days after HCT and its onset and severity
timeFrame: 120 days post-SCT
measure: Incidence of relapse within 180 days after HCT and its onset and severity
timeFrame: 180 days post-SCT
measure: Incidence of CMV DNAemia requiring PET within 100-180 days after HCT
timeFrame: From day 100 to day 180 after HCT
measure: Incidence of non-CMV infections within 180 days after HCT and its onset and severity
timeFrame: 180 days post-SCT
Other outcomes:
Locations:
Study officials:
References: