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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00001790
First Posted: December 10, 2002
Last Update Posted: March 4, 2008
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
National Institutes of Health Clinical Center (CC)
  Purpose
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 an 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 0.5mg/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) and 2.0mg/kg/day (not to exceed 100mg/day). The planned sample size is 64 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 80 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 into 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 50mg/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 2.0mg/kg/day (not to exceed 100mg/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.

Condition Intervention Phase
Fever Mycoses Neutropenia Drug: FK463 Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I Study of the Safety, Tolerance, and Pharmacokinetics of FK463 in Immunocompromised Children With Fever and Neutropenia

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 120
Study Start Date: October 1998
Estimated Study Completion Date: September 2000
Detailed Description:
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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001790


Locations
United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001790     History of Changes
Other Study ID Numbers: 990007
99-C-0007
First Submitted: November 3, 1999
First Posted: December 10, 2002
Last Update Posted: March 4, 2008
Last Verified: October 1999

Keywords provided by National Institutes of Health Clinical Center (CC):
Aspergillosis
Candidiasis
Empiric Therapy
Fungal Infection
Fungemia

Additional relevant MeSH terms:
Fever
Mycoses
Neutropenia
Body Temperature Changes
Signs and Symptoms
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Micafungin
Antifungal Agents
Anti-Infective Agents