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Intermittent Liposomal Amphotericin B Primary Prophylaxis

Primary Purpose

Acute Myeloid Leukemia

Status
Unknown status
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Liposomal amphotericin B
Sponsored by
Bayside Health
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Myeloid Leukemia focused on measuring Prophylaxis, Liposomal Amphotericin B, Acute myeloid leukaemia, Invasive Fungal Infections

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Alfred Hosptial
  • Box Hill Hospital, Eastern HealthRecruiting

Outcomes

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

Full Information

First Posted
March 21, 2007
Last Updated
December 12, 2013
Sponsor
Bayside Health
Collaborators
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT00451711
Brief Title
Intermittent Liposomal Amphotericin B Primary Prophylaxis
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2007
Overall Recruitment Status
Unknown status
Study Start Date
May 2007 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayside Health
Collaborators
Gilead Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Prophylaxis, Liposomal Amphotericin B, Acute myeloid leukaemia, Invasive Fungal Infections

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Liposomal amphotericin B
Primary Outcome Measure Information:
Title
Safety as defined by the incidence of all adverse events occurring by the completion of each trial prophylaxis course.
Secondary Outcome Measure Information:
Title
Safety:
Title
Incidence of renal toxicity
Title
Incidence of hepatotoxicity
Title
Incidence of ionic abnormalitities
Title
Incidence of cardiovascular toxicity
Title
Efficacy:
Title
Incidence of proven or probable IFI
Title
Incidence of superficial fungal infections
Title
Incidence of fever of unknown origin requiring empirical antifungal therapy during any course of prophylaxis
Title
Incidence of IFI-related mortality

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
C. Orla Morrissey, MB, BCh, FRACP
Phone
+61 3 9076 2000
Ext
62631
Email
o.morrissey@alfred.org.au
First Name & Middle Initial & Last Name or Official Title & Degree
Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA
Phone
+61 3 9076 2000
Ext
63393
Email
a.schwarer@alfred.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
C. Orla Morrissey, MB, BCh, FRACP
Organizational Affiliation
The Alfred Hospital, Level 2 Burnet Institute, Commercial Rd., Melbourne, 3004, Victoria, Australia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA
Organizational Affiliation
The Alfred Hospital, Ground Floor South Block, Commercial Rd., Melbourne, Victoria, 3004, Australia
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Alfred Hosptial
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C. Orla Morrissey, MB, BCh, FRACP
First Name & Middle Initial & Last Name & Degree
Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA
First Name & Middle Initial & Last Name & Degree
Sushrat Patil, MB, BS, FRACP, FRCPA
Facility Name
Box Hill Hospital, Eastern Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3129
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA
Phone
+61 3 9895 3333
Email
anthony.schwarer@boxhill.org.au
First Name & Middle Initial & Last Name & Degree
Anthony P. Schwarer, MB, BS, FRACP, MD, FRCPA

12. IPD Sharing Statement

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Intermittent Liposomal Amphotericin B Primary Prophylaxis

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