Letermovir Prophylaxis for Cytomegalovirus (CMV) in Patients With Graft-versus-host Disease

Study Overview
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Brief Summary
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Explore the tolerability and efficacy of letermovir in the prevention of CMV reactivation in patients with acute and chronic graft-versus-host disease (GVHD) beyond day 100.

Detailed Description
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42 patients meeting the inclusion criteria will receive letermovir 480 mg per day. Patients receiving concomitant cyclosporine will receive 240 mg of letermovir. Letermovir will be given during 14 weeks or until prednisone dose is reduced below 0.2 mg / kg / day, whichever comes earlier. All the patients will continue herpesvirus prophylaxis with acyclovir or valacyclovir. Patients will be evaluated biweekly until letermovir discontinuation. A PCR CMV test will be performed biweekly. Patients in whom clinically significant CMV infection (defined as CMV disease or CMV viremia leading to preemptive treatment) develop, will discontinue the trial regimen and begin anti-CMV therapy according to local practice. The threshold for preemptive treatment for CMV viremia will be >1000 copies/ ml.

Official Title
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Letermovir Prophylaxis for CMV in Patients With Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation: a Proof of Concept Multicenter Study

Conditions
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Graft-versus-host-disease, CMV

Intervention / Treatment
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* Drug: Letermovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients After allogeneic transplantation Seropositive for CMV Who already received letermovir prophylaxis until day 100 without CMV reactivation Beyond day 100 after transplantation at enrollment With acute or chronic GVHD Daily prednisone dose ≥ 0.5 mg/kg (or equivalent dose of another glucocorticoid) at enrollment. Negative polymerase chain reaction (PCR) for CMV at enrollment Provided informed consent Exclusion Criteria: Seronegative for CMV Positive PCR for CMV at enrollment Patient has previously had CMV reactivation under letermovir.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letermovir<br>Patients meeting the inclusion criteria will receive letermovir 480 mg per day. Patients receiving concomitant cyclosporine will receive 240 mg of letermovir. Letermovir will be given during 14 weeks or until prednisone dose is reduced below 0.2 mg / kg / day, whichever comes earlier. | Drug: Letermovir<br>* Patients meeting the inclusion criteria will receive letermovir 480 mg per day. Patients receiving concomitant cyclosporine will receive 240 mg of letermovir. Letermovir will be given during 14 weeks or until prednisone dose is reduced below 0.2 mg / kg / day, whichever comes earlier.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of CMV infection | The proportion of patients with clinically significant CMV infection through week 14 after enrollment or until prednisone dose is reduced below 0.2 mg / kg / day, whichever comes earlier. | 14 weeks |