MT2013-37R: Voriconazole Monitoring in Pediatric Stem Cell Transplant Patients

Study Overview
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Brief Summary
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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.

Official Title
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MT2013-37R: Voriconazole Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Patients

Conditions
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Fungal Infection

Intervention / Treatment
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* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 21 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voriconazole<br> | Drug: Voriconazole<br>* 6 mg/kg to 12 mg/kg IV/PO every 12 hours depending on patient age and dose toleration of prior patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated, minimum efficacious dose for 3 different pediatric age groups |  | Seven days after starting voriconazole | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of initial dose of voriconazole with voriconazole blood concentration in 3 different pediatric age groups |  | After starting voriconazole: Day 5, between Days 12-15, between Days 19-22 | 
| Correlation of voriconazole dose with elevations to 5 times the upper limit of normal in liver enzymes |  | After starting voriconazole: Twice a week Days 1-30 and 1 week after the last dose of voriconazole   Day 35-42 | 
| Incidence of fungal infection |  | 6-month period after transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fungal infection, voriconazole, pediatric, stem cell transplant, hematopoietic stem cell transplant