Clinical trial NCT00066599: Voriconazole in Preventing Fungal Infections in Children With Neutropenia After Chemotherapy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Cancer
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Neuroblastoma
Neutropenia
Sarcoma
Keywords: neutropenia
recurrent childhood lymphoblastic lymphoma
stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
stage I childhood small noncleaved cell lymphoma
stage II childhood small noncleaved cell lymphoma
stage III childhood small noncleaved cell lymphoma
stage IV childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
stage I childhood large cell lymphoma
stage II childhood large cell lymphoma
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma
childhood acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
recurrent/refractory childhood Hodgkin lymphoma
stage I childhood Hodgkin lymphoma
stage II childhood Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
childhood acute promyelocytic leukemia (M3)
previously treated childhood rhabdomyosarcoma
recurrent Wilms tumor and other childhood kidney tumors
recurrent childhood rhabdomyosarcoma
childhood chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
intraocular lymphoma
primary central nervous system non-Hodgkin lymphoma
recurrent adult T-cell leukemia/lymphoma
acute undifferentiated leukemia
childhood acute lymphoblastic leukemia in remission
recurrent childhood acute lymphoblastic leukemia
secondary acute myeloid leukemia
untreated childhood acute lymphoblastic leukemia
disseminated neuroblastoma
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent neuroblastoma
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-08-07
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Diego
country: United States
facility: Children's Hospital and Health Center, San Diego
state: California
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
Study officials:
affiliation: National Cancer Institute (NCI)
name: Thomas J. Walsh, MD
role: PRINCIPAL_INVESTIGATOR
References: