Voriconazole in Preventing Fungal Infections in Children With Neutropenia After Chemotherapy

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00066599

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Neuroblastoma Neutropenia Sarcoma	Drug: voriconazole	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

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

Study Start Date :

Jun 1, 2003

Actual Study Completion Date :

Jun 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 11 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Orange County	Orange	California	United States	92868
2	Children's Hospital and Health Center, San Diego	San Diego	California	United States	92123-4282
3	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
4	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
5	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
6	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-4318
7	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390