Ambisome and Management of Culture-negative Neutropenic Fever Unresponsive to Antibiotics

• Status: Terminated
• Trial end date: 2008-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Administration of a single high dose (10 mg/kg) of AmBisome® no later than 72 hours after ARNF onset followed by two 5 mg/kg doses on days 2 and 5 may provide sustained tissue levels of amphotericin B that are as mycologically effective as those provided after administering the standard daily dose of 3 mg/kg/day. The new dosing regimen is anticipated to be equally clinically effective compared with the standard AmBisome® regimen when given for the duration of neutropenic fever in patients with ARNF. In addition, the degree and incidence of nephrotoxicity are predicted to be lower with the 3 sequential dose regimen compared to daily dosing with 3 mg/kg because of the lower cumulative dosage (20 mg/kg versus 42 mg/kg, respectively), which is 1 contributing factor for the development of acute renal failure. Furthermore, the lower cumulative dose may be a cost-effective strategy for the treatment of patients with ARNF.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences
• Treatments: Amphotericin B; Anti-Bacterial Agents; Antibiotics, Antitubercular; Liposomal amphotericin B

Criteria

Inclusion Criteria:

• Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. Adult patients with hematologic malignancy undergoing chemotherapy for leukemia or lymphoma will be recruited into this study from 2 centers provided the following inclusion criteria are fulfilled:

• Male or female

• Age ≥ 18 years

• Neutropenia (< 0.5 x 109 cells/L)

• Received empiric antibiotic treatment for 3 days for blood culture negative infection

• Persistent fever of ≥ 38°C

• No known IFI at baseline during this neutropenic episode. However, patients with "missed" evidence of IFI (features absent at randomization but evidence within 48 hours [eg, positive chest computerized tomography (CT)]) will complete the randomized treatment and kinetic measurements

• No antifungal prophylaxis or treatment in this hospital admission or for the past 30 days

• Baseline liver function tests ≤ 10 times the upper limit of normal and baseline creatinine ≤ 2 times the upper limit of normal

• No known hypersensitivity to amphotericin B or LAMB or any of its constituents, in particular known history of anaphylactic reaction to amphotericin B or LAMB or any of its constituents

• Females of childbearing potential (less than 2 years post menopausal) must be surgically incapable of pregnancy, or practicing an acceptable method of birth control with a negative pregnancy test (blood or urine) at baseline

• Ability to comply with all study requirements

• Written informed consent

Exclusion Criteria:

• Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

• Evidence of proven, probably or possible invasive fungal infection

• Chronic invasive fungal infection, defined as signs/symptoms of invasive fungal infection present for >4 weeks preceding entry into study

• Prior systemic therapy greater or equal to 4 days with any polyene anti-fungal agent within 30 days of study enrollment

• Prior systemic therapy with non-polyenes (i.e., azole or echinochandin derivatives) for the current ARNF. (Prior systemic anti-fungal therapy with non-polyene derivatives for prophylaxis or as empiric therapy for febrile neutropenia is permissible.)

• Use of another investigational, unlicensed drug within 30 days of screening or concurrent participation in another clinical trial using an investigational, unlicensed drug.

• Serum creatinine > 2x upper limit of normal (ULN)

• Serum ALT or AST > 5x ULN

• History of allergy or serious adverse reaction to any polyene anti-fungal agent.

• Patients who have a positive blood culture within 5 days before day 0 with a clinically significant organism isolated from the peripheral blood, who despite appropriate antibiotics have persistent positive cultures

• Pregnant or lactating women.