Intermittent Liposomal Amphotericin B Primary Prophylaxis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00451711
Recruitment Status : Unknown
Verified March 2007 by Bayside Health.
Recruitment status was:  Recruiting
First Posted : March 23, 2007
Last Update Posted : December 16, 2013
Gilead Sciences
Information provided by (Responsible Party):
Bayside Health

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Liposomal amphotericin B Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : May 2007
Estimated Study Completion Date : October 2014

Primary Outcome Measures :
  1. Safety as defined by the incidence of all adverse events occurring by the completion of each trial prophylaxis course.

Secondary Outcome Measures :
  1. Safety:
  2. Incidence of renal toxicity
  3. Incidence of hepatotoxicity
  4. Incidence of ionic abnormalitities
  5. Incidence of cardiovascular toxicity
  6. Efficacy:
  7. Incidence of proven or probable IFI
  8. Incidence of superficial fungal infections
  9. Incidence of fever of unknown origin requiring empirical antifungal therapy during any course of prophylaxis
  10. Incidence of IFI-related mortality

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00451711

Contact: C. Orla Morrissey, MB, BCh, FRACP +61 3 9076 2000 ext 62631
Contact: Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA +61 3 9076 2000 ext 63393

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 Recruiting
Melbourne, Victoria, Australia, 3129
Contact: Anthony P Schwarer, MB, BS, FRACP, MD, FRCPA    +61 3 9895 3333   
Principal Investigator: Anthony P. Schwarer, MB, BS, FRACP, MD, FRCPA         
Sponsors and Collaborators
Bayside Health
Gilead Sciences
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

Responsible Party: Bayside Health Identifier: NCT00451711     History of Changes
Other Study ID Numbers: IN-AU-131-0176
First Posted: March 23, 2007    Key Record Dates
Last Update Posted: December 16, 2013
Last Verified: March 2007

Keywords provided by Bayside Health:
Liposomal Amphotericin B
Acute myeloid leukaemia
Invasive Fungal Infections

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Amphotericin B
Liposomal amphotericin B
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antifungal Agents