Voriconazole in Preventing or Treating Fungal Infections in Younger Patients Undergoing Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated, minimum efficacious dose (MTD, MED) of voriconazole for different pediatric age groups undergoing bone marrow transplantation, specifically what starting voriconazole dose correlates with a concentration in the therapeutic range for each age group without excessive toxicity.

SECONDARY OBJECTIVES:

I. How the initial dose correlates with voriconazole concentration for each age group.

II. To determine what voriconazole dose correlates with elevations to 5 times the upper limit of normal in liver enzymes.

III. To estimate incidence of fungal infection within 6 months post-transplant.

TERTIARY OBJECTIVES:

I. To characterize the effect of genetic polymorphisms within family 2, subfamily C, polypeptide 19 (2C19), flavin mono-oxygenase-3 (FMO-3), and NAD(P)H dehydrogenase, quinone 1 (NQO1) on voriconazole and voriconazole N-oxide pharmacokinetic variability in pediatric patients receiving allogeneic hematopoietic stem cell transplant (HSCT).

II. To characterize the effect of patient specific characteristics including age, gender, primary disease, hepatic function, creatinine clearance and concomitant medications on voriconazole and voriconazole N-oxide pharmacokinetic variability in pediatric patients receiving allogeneic HSCT.

OUTLINE: This is a dose-escalation study.

Patients receive voriconazole intravenously (IV) or orally (PO) every 12 hours on days 1-30 after HSCT. Patients may continue voriconazole as medically appropriate independent of this study.

After completion of study treatment, patients are followed up for 1 week.