Clinical trial NCT02227797: MT2013-37R: Voriconazole Monitoring in Pediatric Stem Cell Transplant Patients
Official title: MT2013-37R: Voriconazole Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fungal Infection
Keywords: stem cell transplant
hematopoietic stem cell transplant
fungal infection
voriconazole
pediatric
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2014-08-28
Enrollment: 66
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to identify the optimal dose of voriconazole, an anti-fungal drug often used in people undergoing stem cell transplant. An optimal dose level is one level that provides a good blood level (concentration) of voriconazole without too much toxicity.


Eligibility criteria: Inclusion Criteria:

* Any patient undergoing allogeneic hematopoietic stem cell transplantation (either 1st or subsequent)
* Age ≤ 21 years
* Adequate organ function within 14 days of enrollment, i.e. Creatinine: \< 1.5 x ULN and Hepatic: ALT, AST and total bilirubin \< 3 x ULN
* Requires voriconazole to prevent or treat invasive fungal infection after undergoing stem cell transplantation

Exclusion Criteria:

* Has received voriconazole within 5 days prior to starting study therapy
* History of hypersensitivity or severe intolerance to azoles
* History, or current evidence, of cardiac arrhythmias defined as QTc ≥ 480 mm/sec
* Receiving the following drugs and cannot be discontinued at least 24 hours before starting therapy: pimozide, quinidine, astemizole, ergot alkaloids.
* Received one or more of the following drugs within 14 days prior to starting study, as they are potent inducers of hepatic microsomal enzymes: rifampin, rifabutin, carbamazepine, phenytoin, nevirapine, long-acting barbiturates.
* Received sirolimus within the 14 days prior to starting study as voriconazole is a potent inhibitor of sirolimus metabolism
* Receiving or anticipated need for methadone as co-administration with voriconazole potentially increases methadone exposure

Primary outcomes:
measure: Maximum tolerated, minimum efficacious dose for 3 different pediatric age groups
timeFrame: Seven days after starting voriconazole
Secondary outcomes:
measure: Correlation of initial dose of voriconazole with voriconazole blood concentration in 3 different pediatric age groups
timeFrame: After starting voriconazole: Day 5, between Days 12-15, between Days 19-22
measure: Correlation of voriconazole dose with elevations to 5 times the upper limit of normal in liver enzymes
timeFrame: After starting voriconazole: Twice a week Days 1-30 and 1 week after the last dose of voriconazole ~ Day 35-42
measure: Incidence of fungal infection
timeFrame: 6-month period after transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Angela Smith, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Masonic Cancer Center, Univeristy of Minnesota
name: Pui-Yang Iroh Tam, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Takahashi T, Jaber MM, Smith AR, Jacobson PA, Fisher J, Kirstein MN. Predictive Value of C-Reactive Protein and Albumin for Temporal Within-Individual Pharmacokinetic Variability of Voriconazole in Pediatric Patients Undergoing Hematopoietic Cell Transplantation. J Clin Pharmacol. 2022 Jul;62(7):855-862. doi: 10.1002/jcph.2024. Epub 2022 Feb 19.