Intermittent Liposomal Amphotericin B Primary Prophylaxis

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00451711
• Other study ID #: IN-AU-131-0176
• Status: Recruiting
• Phase: Phase 2
• First received: March 21, 2007
• Last updated: December 12, 2013
• Start date: May 2007
• Est. completion date: October 2014

Study information

• Verified date: March 2007
• Source: Bayside Health
• Contact: C. Orla Morrissey, MB, BCh, FRACP
• Phone: +61 3 9076 2000
• Email: o.morrissey[@]alfred.org.au
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Liposomal amphotericin B

Locations

Country	Name	City	State
Australia	Box Hill Hospital, Eastern Health	Melbourne	Victoria
Australia	The Alfred Hosptial	Melbourne	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
Bayside Health	Gilead Sciences

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as defined by the incidence of all adverse events occurring by the completion of each trial prophylaxis course.
Secondary	Safety:
Secondary	Incidence of renal toxicity
Secondary	Incidence of hepatotoxicity
Secondary	Incidence of ionic abnormalitities
Secondary	Incidence of cardiovascular toxicity
Secondary	Efficacy:
Secondary	Incidence of proven or probable IFI
Secondary	Incidence of superficial fungal infections
Secondary	Incidence of fever of unknown origin requiring empirical antifungal therapy during any course of prophylaxis
Secondary	Incidence of IFI-related mortality