Fever and infection are serious complications when a person's white blood cell count becomes low. A condition called neutropenia occurs when the white blood cell count is below 500cells/mm. Fungi are one kind of germ that causes severe infection in patients with neutropenia.

The purpose of this study is to determine the side effects and pharmacokinetics (the way the body handles the drug) of a new antifungal medicine, anidulafungin. Researchers hope that this drug will prevent life-threatening fungal infections from occurring in patients who are neutropenic.

Twenty-four children age 2 to 17 will be enrolled. Participants will receive anidulafungin at the onset of fever and neutropenia. Participants will take anidulafungin once day via a catheter in the vein for a maximum of 28 days. Depending on when they entered the study, participants will receive one of two dosage levels. Small amounts of blood will be drawn periodically to measure drug levels and to check for side effects. The doctor will check each participant closely during the study for fungal infection. If a fungal infection develops, the child will be taken off anidulafungin and treated with other drugs.

Condition	Treatment or Intervention	Phase
Fever Neutropenia	Drug: Anidulafungin	Phase II

Further Study Details: 

Expected Total Enrollment:  25

The objective of this study is to evaluate the safety, tolerance and pharmacokinetics of anidulafungin administered intravenously as early empirical therapy for prevention of fungal infections in neutropenic children. The secondary objective will be to assess the frequency of children who develop documented deeply invasive fungal infections while receiving anidulafungin for early empirical therapy. The study is designed as a multi-center, open-label, sequential dose-escalation study of intravenous anidulafungin. Intravenous anidulafungin will be administered daily to patients with neutropenia (absolute neutrophil count less than or equal to 500/mm(3)). The patient population consists of children ages 2 to 17 years of age; two age cohorts will be studied (2-11 and 12-17). Dosage levels will be 0.75mg/kg/day (not to exceed 50mg/day) and 1.5mg/kg/day (not to exceed 100mg/kg/day). The planned sample size is 24 patients. At each dosage level, a total of 6 patients will be enrolled into each age cohort (2-11, 12-17); a total of 12 patients will be enrolled at each dosage level. The first 12 patients will receive anidulafungin at a loading dose of 1.5mg/kg/day (not to exceed 100mg/day) followed by a maintenance dose of 0.75mg/kd/day (not to exceed 50mg/day). The second set of 12 patients will receive anidulafungin at a loading dose of 3.0mg/kg/day (not to exceed 200mg/day) followed by a maintenance dose of 1.5mg/kg/day (not to exceed 100mg/day). Study drug will be administered for at least five days and will continue until recovery from neutropenia (ANC greater than 500/mm(3)) or until the initiation of standard of care for either empirical antifungal therapy or for proven fungal infection. Patients may receive anidulafungin for a maximum duration of 28 days.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Children ages 2-17.
Expected ten day duration of neutropenia due to cytotoxic chemotherapy or aplastic anemia.
Neutropenia defined as either less than 500 absolute neutrophil cont/mm (3) or presentation with greater than 500 but less than 1000 with the anticipation that the counts will fall below 500 within 72 hours.
Informed consent of the patient, parent or legally authorized representative obtained prior to entry.
Verbal assent will be obtained from minors capable of understanding.
The patient and parent(s), (or legally authorized representative of the child), will be available for the duration of the study and able to abide by the study restrictions.
EXCLUSION CRITERIA:
Patients with proven deeply invasive fungal infection that has been confirmed prior to study entry by the MSG/EORTC criteria.
Patient is pregnant, breast feeding or planning a pregnancy during the course of the study.
Sexually active male and female patients not using an acceptable barrier method of contraception or practicing abstinence throughout the study and for at least 30 days after receiving their last treatment unless the patient is surgically or medically sterile.
The anticipation of not being able to complete the study, including receiving less than 5 days of anidulafungin.
Patients with moderate or severe liver disease, as defined by:
a. AST or ALT greater that 5 times upper limit of normal (ULN) or
b. Total bilirubin greater than 2.5 tines ULN
Patients with a calculated creatinine clearance less than 30ml/min.
Patients who require treatment with systemic antifungal agents other than anidulafungin (Oral , non-absorbable azoles are permitted).
Patients with a history of anaphylaxis attributed to the echinocandin class of antifungals.
Use of an investigational drug (without any FDA approved indications) within 4 weeks before the first dose of anidulafungin.
Any other concomitant condition, which in the opinion of the investigator, would preclude a patient's participation in the study.
Previous participation in the study.
Previous exposure to anidulafungin.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States

Study ID Numbers:  030229; 03-C-0229
Record last reviewed:  October 22, 2004
Last Updated:  October 23, 2004
Record first received:  June 26, 2003
ClinicalTrials.gov Identifier:  NCT00063466
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08