A Study of the Drug Letermovir as Prevention of Cytomegalovirus Infection After Stem Cell Transplant in Pediatric Patients
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age2-18
SponsorChildren's Oncology Group
About this trial
This phase III single arm trial determines whether taking prophylactic letermovir will reduce the likelihood of infection with cytomegalovirus (CMV) in children and adolescents after stem cell transplant compared to estimated rate of infection without prophylaxis. The treatments used to prepare for hematopoietic cell transplant (HCT) reduce the body's natural infection-fighting ability and increase the likelihood of an infection with a virus called cytomegalovirus. "Prophylaxis" means to take a drug to prevent a disease or side effect. Letermovir is an antiviral drug that stops cytomegalovirus from multiplying and may prevent cytomegalovirus infection and make the disease less severe.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
>= 2 years and < 18 years at the time of enrollment
Weight must be >= 6 kg at the time of enrollment
Planned allogeneic HCT (bone marrow, peripheral blood stem cell, or cord blood transplant)
Patient must be CMV sero-positive (i.e., recipient CMV immunoglobulin G positive)
Disqualifiers
Expected inability to tolerate oral formulation of letermovir
Hypersensitivity to letermovir or any component of the formulation
History of CMV end organ disease within 6 months (180 days) prior to enrollment
Note: CMV end organ disease based on proposed definitions by Ljungman et al. and inclusive of proven, probable or possible disease
Trial design
Design model
Parallel
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Letermovir
DrugGiven PO or IV
Treatment groups
105 Participants
are divided into 2 treatment groupsGroup A: ARM A (Letermovir prophylaxis)Experimental treatment 2 interventions
Group B: Arm B (No prophylaxis)Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
Clinically significant cytomegalovirus (CMV) infection
Clinically significant CMV is defined as the first of (1) initiation of anti-CMV preemptive therapy for documented CMV DNAemia or (2) onset of CMV end-organ disease. Will estimate the 14 week cause-specific cumulative incidence of clinically significant CMV under the non-parametric, Aalen-Johansen estimator of the cumulative incidence function. Will estimate the 95% upper 1-sided confidence limit of the cause-specific cumulative incidence at 100-days post-hematopoietic cell transplantation using a bias-corrected and accelerated bootstrap-based confidence interval.
Time frame
Up to week 14 post-transplantSecondary outcomes
1
Detection of CMV DNAemia
Will estimate the cumulative incidence of CMV DNAemia at 24-weeks post-transplant by study arm and will report the corresponding 95% confidence intervals.
Time frame
Up to week 24 post-transplant2
CMV-free survival
Will estimate the cumulative incidence of the occurrence of CMV DNAemia or death by week 24 post-transplant by study arm and will report the corresponding 95% confidence intervals.
Time frame
Up to 24 weeks post-transplantOther outcomes
1
Clinically significant CMV infection in early follow up
Clinically significant CMV is defined as the first of (1) initiation of anti-CMV preemptive therapy for documented CMV DNAemia or (2) onset of CMV end-organ disease. Will estimate the cumulative incidence of clinically significant CMV at 24-weeks post-transplant and will report the corresponding 95% confidence interval.
Time frame
Up to 24 weeks post-transplant2
Clinically significant CMV infection in late follow up
Clinically significant CMV is defined as the first of (1) initiation of anti-CMV preemptive therapy for documented CMV DNAemia or (2) onset of CMV end-organ disease. Will estimate the cumulative incidence of clinically significant CMV at 52-weeks post-transplant and will report the corresponding 95% confidence interval.
Time frame
Up to 52 weeks post-transplant3
Overall survival (OS) in early follow up
The Kaplan-Meier method will be used to estimate the 24-week OS probability, as defined by time from transplant until death. The corresponding 95% confidence interval will be reported.
Time frame
Up to 24 weeks post-transplant4
Overall survival (OS) in late follow up
The Kaplan-Meier method will be used to estimate the 52-week OS probability, as defined by time from transplant until death. The corresponding 95% confidence interval will be reported.
Time frame
Up to 52 weeks post-transplantSponsors and contacts
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Source ClinicalTrials.gov