Intermittent Liposomal Amphotericin B Primary Prophylaxis
Recruitment status was: Recruiting
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Randomised, Stratified, Open Label, Phase II Pilot Study on the Safety of a Daily, Intermittent, or Weekly Administration of 1, 3 or 10mg/kg of AmBisome® in Antifungal Primary Prophylaxis of High-Risk Patients With Acute Myeloid Leukaemia|
- Safety as defined by the incidence of all adverse events occurring by the completion of each trial prophylaxis course.
- Incidence of renal toxicity
- Incidence of hepatotoxicity
- Incidence of ionic abnormalitities
- Incidence of cardiovascular toxicity
- Incidence of proven or probable IFI
- Incidence of superficial fungal infections
- Incidence of fever of unknown origin requiring empirical antifungal therapy during any course of prophylaxis
- Incidence of IFI-related mortality
|Study Start Date:||May 2007|
|Estimated Study Completion Date:||October 2014|
Invasive Fungal Infections (IFI)are a significant cause of death in patients with acute leukaemia who are undergoing chemotherapy. This is despite improvements in antifungal therapy for the treatment of IFI. The major reason for this is that the current standard diagnostic tests of culture and biopsy lack the ability to make a diagnosis, either early or accurately. Thus other strategies such as the use of prophylaxis are needed. Several antifungal agents have been trialled as prophylaxis but all have disadvantages that limit their effectiveness.
Liposomal amphotericin B(LAB) is a broad spectrum antifungal agent that kills fungal cells. When given in high doses intermittently it supersaturates the liver and the overspill into the bloodstream is absorbed by tissues such as lung, brain and kidneys (i.e. sites where IFI are likely to occur). This effect has been shown in a number of animal and laboratory test-tube studies to reduce fungal burden, improve survival and maintain adequate levels of the drug in between doses. However no intermittent high-dose prophylaxis study has been done in humans. Thus before we proceed to a randomised controlled clinical trial of the efficacy of intermittent high-dose LAB compared with another antifungal agent it is necessary to determine in a phase 2 study which of 2 intermittent dosing LAB regimens (i.e. 3mg/kg three times a week or 10mg/kg once a week) administered during the neutropenic phase of induction-consolidation chemotherapy for treatment of acute leukaemia is safest and best tolerated compared to the standard dosing regimen of 1mg/kg daily of LAB.
Males and females aged >18 years who are undergoing intensive combination chemotherapy for acute leukaemia will be randomised 1:1:1 to either 1mg/kg daily; 3mg/kg 3 times a week or 10mg/kg once weekly of intravenous liposomal amphotericin B. The 3 arms will be compared for the safety of the 3 dosing regimens.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00451711
|The Alfred Hosptial|
|Melbourne, Victoria, Australia, 3004|
|Box Hill Hospital, Eastern Health|
|Melbourne, Victoria, Australia, 3129|
|Principal Investigator:||C. Orla Morrissey, MB, BCh, FRACP||The Alfred Hospital, Level 2 Burnet Institute, Commercial Rd., Melbourne, 3004, Victoria, Australia|
|Principal Investigator:||Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA||The Alfred Hospital, Ground Floor South Block, Commercial Rd., Melbourne, Victoria, 3004, Australia|