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Phase I Study of the Safety, Tolerance, and Pharmacokinetics of FK463 in Immunocompromised Children With Fever and Neutropenia


Phase 1
N/A
N/A
Not Enrolling
Both
Fever, Mycoses, Neutropenia

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Trial Information

Phase I Study of the Safety, Tolerance, and Pharmacokinetics of FK463 in Immunocompromised Children With Fever and Neutropenia


The objective of this study is to evaluate the safety, tolerance, and pharmacokinetics of
FK463, a novel echinocandin (cell wall-active antifungal lipopeptide), as early empirical
therapy for prevention of fungal infections in immunocompromised children. The study is
designed as a multicenter open label, sequential dose escalation study of intravenous FK463.
Intravenous FK463 will be administered daily as a one hour infusion to patients with new
onset of fever and neutropenia (absolute neutrophil count less than or equal to 500/mm3) who
will be initiated onto broad spectrum empirical antibacterial therapy. The patient
population consists of children ages 2 to 17 years of age; two age cohorts will be studied
(2-12, 13-17). Dosage levels will be 0.5 mg/kg/day (not to exceed 25 mg/day), 1.0 mg/kg/day
(not to exceed 50 mg/day), 1.5 mg/kg/day (not to exceed 75 mg/day). 2.0 mg/kg/day (not to
exceed 100 mg/day), 3.0 mg/kg/day (not to exceed 150 mg/day) and 4.0 mg/kg/day (not to
exceed 200 mg/day). The planned sample size is 96 patients (a maximum of two replacement
patients may be added to a given dose level and age cohort, for a total of no more than 10
patients per dose level and age cohort. The study will enroll no more than 120 patients).
At each dosage level, a total of 8 patients will be enrolled into each age cohort (2-12,
13-17); a total of 16 patients will be enrolled at each dosage level. The first group of
patients will receive FK463 at 0.5 mg/kg/day (not to exceed 25 mg/day). The second group of
patients will receive 1.0 mg/kg/day (not to exceed 50 mg/day). The third group of patients
will receive 1.5 mg/kg/day (not to exceed 75 mg/day). The fourth group of patients will
receive 2.0 mg/kg/day (not to exceed 100 mg/day). The fifth group of patients will receive
3.0 mg/kg/day (not to exceed 150 mg/day). The sixth group of patients will receive 4.0
mg/kg/day (not to exceed 200 mg/day). Study drug will continue until recovery from
neutropenia (ANC post nadir greater than or equal 250/mm3) or until the initiation of
conventional deoxycholate amphotericin B or a lipid formulation of amphotericin B for
empirical antifungal therapy or for proven fungal infection. Patients may receive FK463 for
a maximum duration of 14 days. For any patient who meets institutional criteria to start
standard empirical antifungal therapy with conventional deoxycholate amphotericin B or a
lipid formulation of amphotericin B (greater than 96 hours on study drug) or who has a
proven breakthrough fungal infection, FK463 will be discontinued and conventional
deoxycholate amphotericin B or a lipid formulation of amphotericin B will be initiated.

Inclusion Criteria


Children ages 2-17 with neutropenia (absolute count less than or equal 5000/mm(3)) and one
or more of the following conditions: leukemia or lymphoma, excluding those patient's on
maintenance therapy; bone marrow or peripheral stem cell transplantation; aplastic anemia;
myelodysplastic syndrome; chemotherapy anticipated to incur greater than 10 days of
neutropenia.

Patients with new onset of fever during neutropenia who will be initiated onto broad
spectrum empirical antibacterial therapy.

Patients must have sufficient venous access to permit administration of study drug,
collection of pharmacokinetic samples and monitoring of safety variables.

Concomitant therapies: Patients may have received or continue to receive antineoplastic
therapies and medications for supportive care.

Females of childbearing potential must have a negative pregnancy test and must agree to
use barrier methods of contraception throughout the study.

Informed consent of the patient, parent, or legally authorized representative obtained
prior to entry.

Verbal assent will be obtained from minors capable of understanding.

No patients with active proven deeply invasive fungal infection.

No patients with moderate or severe liver disease, as defined by: AST or ALT greater than
2.5 times the upper limit of normal or total bilirubin greater than 2.5 times the upper
limit of normal.

No patients who have received intravenous amphotericin B or formulations of amphotericin B
within 72 hours of entering the study or who require treatment with systemic antifungal
agents other than FK463. Patients may continue to receive fluconazole prophylactically
(no more than 400mg/day or 12mg/kg/day) while on study. All other systemic antifungals
agents must be discontinued prior to the first dose of FK463.

No patients who are on other phase I trials of investigational agents.

No patients previously enrolled into this study.

No other concomitant condition which, in the opinion of the investigator, would preclude a
patient's participation in the study.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Authority:

United States: Federal Government

Study ID:

990007

NCT ID:

NCT00001790

Start Date:

October 1998

Completion Date:

September 2000

Related Keywords:

  • Fever
  • Mycoses
  • Neutropenia
  • Aspergillosis
  • Candidiasis
  • Empiric Therapy
  • Fungal Infection
  • Fungemia
  • Fever
  • Mycoses
  • Neutropenia

Name

Location

National Cancer Institute (NCI)Bethesda, Maryland  20892