Official Title: “An Open-Label, Intravenous To Oral Switch, Multiple Dose, Multi-Center Study To Investigate The Pharmacokinetics, Safety And Tolerability Of Voriconazole In Hospitalized Children Aged 2 - <12 Years Who Require Treatment For The Prevention Of Systemic Fungal Infection”

RATIONALE: Voriconazole may be effective in preventing systemic fungal infections following chemotherapy.

PURPOSE: Phase II trial to study the effectiveness of voriconazole in preventing systemic fungal infections in children who have neutropenia after receiving chemotherapy for leukemia, lymphoma, or aplastic anemia or in preparation for bone marrow or stem cell transplantation.

Study Type: Interventional

Study Design: Supportive Care, Open Label

OBJECTIVES: - Determine the pharmacokinetics of voriconazole administered IV and orally for the prevention of systemic fungal infection in pediatric patients with neutropenia after chemotherapy. - Determine the safety and tolerability of this drug in these patients.

OUTLINE: This is a pilot, open-label, multicenter study. Patients are stratified according to age (2 to 5 vs 6 to 11).

Within 48 hours after completion of chemotherapy, patients begin prophylactic therapy: - Cohort 1 (the first 18 patients, 9 per stratum): Patients receive voriconazole IV over 80-160 minutes twice daily on days 1-8 and oral voriconazole* twice daily beginning on day 9.

Depending on the results of the interim pharmacokinetic analysis, the last 18 patients entered on the study receive 1 of the following regimens: - Cohort 2A:Patients receive voriconazole as in cohort 1 at a higher dose. - Cohort 2B: Patients receive voriconazole IV over 80-160 minutes twice daily on days 1-4 and oral voriconazole* twice daily beginning on day 5.

NOTE: *Patients who are unable to tolerate oral medication may continue receiving IV medication until day 20.

In all cohorts, treatment continues until blood counts recover or day 30 in the absence of unacceptable toxicity or progression of infection.

Patients are followed at 30 days and at 12 months.

PROJECTED ACCRUAL: A total of 49 patients (approximately 24 per stratum) were accrued for this study within 1 year.

Intervention(s) in this Clinical Trial

• Drug: voriconazole

DISEASE CHARACTERISTICS:

• Expected to develop neutropenia (absolute neutrophil count less than 500/mm^3) lasting for more than 10 days after chemotherapy for 1 of the following conditions:
• Leukemia
• Lymphoma
• Aplastic anemia
• Preparation for a bone marrow or stem cell transplantation
• Requiring treatment for the prevention of systemic fungal infection

PATIENT CHARACTERISTICS:

• Age
• 2 to 11
• Performance status
• Not specified
• Life expectancy
• More than 3 months
• Hematopoietic
• See Disease Characteristics
• Hepatic
• AST and ALT no greater than 5 times upper limit of normal (ULN)
• Bilirubin no greater than 5 times ULN
• Renal
• Creatinine clearance at least 30 mL/min
• Cardiovascular
• No cardiac arrhythmia
• Other
• Not pregnant or nursing
• Negative pregnancy test
• No severe hypokalemia (potassium less than 3.2 mmol/L)
• No prior hypersensitivity to or severe intolerance of azole antifungal agents
• No other concurrent condition that would preclude study therapy

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• See Disease Characteristics
• Chemotherapy
• See Disease Characteristics
• Endocrine therapy
• Not specified
• Radiotherapy
• Not specified
• Surgery
• Not specified
• Other
• At least 24 hours since prior use of any of the following:
• Terfenadine
• Pimozide
• Quinidine
• Astemizole
• Cisapride
• Omeprazole
• More than 14 days since prior use of any of the following:
• Rifampin
• Rifabutin
• Carbamazepine
• Phenytoin
• Nevirapine
• Long-acting barbiturates
• No prior sirolimus
• No prior enrollment on this study
• No concurrent use of any of the following:
• Terfenadine
• Pimozide
• Quinidine
• Astemizole
• Cisapride
• Omeprazole
• No other concurrent investigational drugs except any of the following:
• Drugs used as treatment for cancer
• Antiretroviral agents
• Drugs used for the treatment of any AIDS-defining opportunistic infections
• No concurrent enrollment in investigational anticancer drug trials that exclude the use of other investigational agents

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: 11 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

Thomas J. Walsh, MD Principal Investigator NCI - Pediatric Oncology Branch  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00066599

Study ID Number: CDR0000316329

ClinicalTrials.gov Identifier: NCT00066599

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database