Letermovir for the Prevention of Cytomegalovirus Reactivation in Patients With Hematological Malignancies Treated With Alemtuzumab

Inclusion Criteria

• Confirmed diagnosis of T-cell or B-cell prolymphocytic leukemia, chronic lymphocytic leukemia, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, or Sezary syndrome
• Intent to treat with alemtuzumab. Monotherapy or combination with chemotherapy is allowed
• Confirmed seropositivity for CMV IgG (>= 0.7 U/mL) within 1 year of first letermovir dose
• Confirmed lack of active CMV infection as evidenced by:
• Undetectable CMV deoxyribonucleic acid (DNA) by Abbott RealTime CMV in vitro polymerase chain reaction assay ( 4 months
• Eastern Cooperative Oncology Group (ECOG) performance status = 5 times the upper limit of normal (ULN) or serum total bilirubin > 2.5 x ULN
• Note: Subjects who meet this exclusion criterion may, at the discretion of the investigator, have one repeat testing done. If the repeat value does not meet this criterion, they may continue in the screening process. Only the specific out of range value should be repeated (not the entire panel)
• Both moderate hepatic insufficiency AND moderate renal insufficiency:
• Moderate hepatic insufficiency is defined as Child Pugh Class B
• Moderate renal insufficiency is defined as a creatinine clearance less than 50 mL/min, as calculated by the Cockcroft-Gault equation
• Cytopenias are NOT an exclusion criteria in this trial as cytopenias are common in this patient population and letermovir has no known adverse effects on blood counts. Patients will be treated per institutional standard of care with as needed transfusions and growth factor support
• Received any of the following drugs within 7 days of enrollment or plans to receive any of the following during the study:
• Ganciclovir
• Valganciclovir
• Foscarnet
• Acyclovir (at doses > 3200 mg PO per day or > 25 mg/kg IV per day)
• Valacyclovir (at doses > 3000 mg PO per day)
• Famciclovir (at doses > 1500 mg PO per day)
• Cyclosporine A
• Pimozide
• Ergot alkaloids (ergotamine and dihydroergotamine)
• Atorvastatin at doses greater than 20 mg daily
• Received any of the following within 30 days prior to enrollment
• Cidofovir
• CMV hyper-immune globulin
• Any investigational CMV antiviral agent/biologic therapy
• Infection or underlying disease necessitating ongoing use of prohibited medications
• Suspected or known hypersensitivity to active or inactive ingredients of letermovir formulations
• Positive at the time of screening for:
• Human immunodeficiency virus (HIV) with CD4 count < 350. If HIV positive, must remain on antiretroviral therapy that is not anticipated to interact with letermovir throughout study
• Hepatitis B surface antigen or core antibody positivity associated with detectable viral load. For any patient with serologic evidence of prior infection but undetectable viral load, viral load and surface antigen will be monitored every 2 weeks. Those with evidence of reactivation (detectable viral load) will be treated with entecavir or lamivudine. Upon resolution of detectable viral load, the patient will be allowed to continue on trial assuming adequate liver function as defined above. Alternatively, patients may be put on prophylactic entecavir or lamivudine to prevent hepatitis B reactivation at the investigator's discretion
• Hepatitis C if no prior or current curative antiviral therapy. For those currently on curative antiviral therapy, they will be allowed on trial if hepatitis C virus (HCV) quantitation is below the limit of detection and adequate liver function as above
• Pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 90 days after the last dose of study therapy
• Expecting to donate eggs or sperm starting from the time of consent through 90 days after the last dose of study therapy
• Currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5X half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer,