Intermittent Liposomal Amphotericin B Primary Prophylaxis - Full Text View

Sponsor:	Bayside Health
Collaborator:	Gilead Sciences
Information provided by:	Bayside Health
ClinicalTrials.gov Identifier:	NCT00451711

Purpose

The purpose of this trial is to see which dose of liposomal amphotericin B is the safest when used as a preventer against invasive fungal infection in patients with acute leukaemia who are undergoing chemotherapy.

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: Liposomal amphotericin B	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study 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

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Fungal Infections Leukemia Molds

Drug Information available for: Amphotericin B

U.S. FDA Resources

Further study details as provided by Bayside Health:

Primary Outcome Measures:

Safety as defined by the incidence of all adverse events occurring by the completion of each trial prophylaxis course.

Secondary Outcome Measures:

Safety:
Incidence of renal toxicity
Incidence of hepatotoxicity
Incidence of ionic abnormalitities
Incidence of cardiovascular toxicity
Efficacy:
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

Estimated Enrollment:	60
Study Start Date:	May 2007
Estimated Study Completion Date:	October 2009

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients fulfilling all the following criteria will be eligible:

Male or female aged >18years;
Newly diagnosed with acute myeloid leukaemia and undergoing first induction chemotherapy regimen;
Expected to have absolute neutrophil counts of <0.5x109/L for at least 2 weeks;
Normal high resolution chest and sinus CT scan at baseline;
No signs or symptoms of invasive fungal infections
No prior diagnosis of proven or probable invasive fungal infection within the last 6 months;
Females of childbearing potential must be: surgically incapable of pregnancy; or practicing an acceptable mode of birth control and have a negative pregnancy test (blood or urine) at baseline;
Give written informed consent prior to any study-specific procedures;
Must have the ability and must agree to comply with all study requirements.

Exclusion Criteria:

Patients with any of the following will be ineligible

Known hypersensitivity to amphotericin B, in particular known history of anaphylactic reaction to amphotericin B;
Patients undergoing any transplantation;
Creatinine clearance <60mL/min/1.72 m2;
Patients with moderate or severe liver disease as defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN)
Patients who are unlikely to survive more than one month;
Patients who have received systemic antifungal therapy within the last 15 days
Any severe cardiovascular disease ( in particular arrhythmias) which may constitute a contra-indication to LAB (AmBisome®) administration;
Any severe diseases other than acute myeloid leukaemia which in the investigator’s judgement may interfere with study evaluations or affect the patients safety;
Pregnant or nursing females;
Patients previously included in this study;
Patients who have taken an investigational drug in the last 30 days prior to the inclusion.
Patients enrolled in a pre-emptive treatment strategy trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00451711

Contacts

Contact: C. Orla Morrissey, MB, BCh, FRACP	+61 3 9076 2000 ext 62631	o.morrissey@alfred.org.au
Contact: Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA	+61 3 9076 2000 ext 63393	a.schwarer@alfred.org.au

Locations

Australia, Victoria
The Alfred Hosptial	Not yet recruiting
Melbourne, Victoria, Australia, 3004
Principal Investigator: C. Orla Morrissey, MB, BCh, FRACP
Principal Investigator: Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA
Sub-Investigator: Sushrat Patil, MB, BS, FRACP, FRCPA
Box Hill Hospital, Eastern Health	Not yet recruiting
Melbourne, Victoria, Australia, 3129
Contact: Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA +61 3 9895 3333 anthony.schwarer@boxhill.org.au
Principal Investigator: Anthony P. Schwarer, MB, BS, FRACP, MD, FRCPA

Sponsors and Collaborators

Bayside Health

Gilead Sciences

Investigators

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

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00451711 History of Changes
Other Study ID Numbers:	IN-AU-131-0176
Study First Received:	March 21, 2007
Last Updated:	March 21, 2007
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Bayside Health:

Prophylaxis
Liposomal Amphotericin B
Acute myeloid leukaemia
Invasive Fungal Infections

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Amphotericin B
Liposomal amphotericin B
Amebicides

Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on February 09, 2012