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PROPHYSOME: Pilot Study on Safety of a Weekly Administration of 10mg/kg of AmBisome® in Antifungal Prophylaxis Treatment of Allogeneic Stem-cell Transplantation and Acute Leukaemia

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Ambisome
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Leukemia focused on measuring antifungal prophylaxis, allogeneic stem-cell transplantation, acute leukaemia, antifungal prophylaxis treatment of allogeneic stem-cell transplantation and acute leukaemia

Eligibility Criteria

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

Inclusion Criteria: Male or female patients aged more than 18, Patients undergoing standard myelo-ablative, conditioning regimen and AGVHD ciclosporin prophylaxis for allogeneic stem cell transplantation, or Patients with acute leukaemia undergoing first induction therapy or second induction therapy after relapse, or consolidation therapy, Expected neutropenia < 0.5 giga/l for at least 2 weeks, Normal chest CT scan and/or normal X-ray of the chest at baseline, Patients with no sign or symptoms of fungal infection and no previous proven or probable IFI, Females of childbearing potential must be surgically incapable of pregnancy, or practising an acceptable method of birth control with a negative pregnancy test (blood or urine) at baseline, Understanding of the study and agreement of the patient to give written informed consent, Ability and agreement to comply with all study requirements, Patient willing to attend hospital appointments for each injection (infusions will be performed in hospital, under strict medical supervision). All patients will be hospitalised prior to, and remain in hospital for at least one day, after the first infusion. Exclusion Criteria: Known hypersensitivity to amphotericin B, in particular known history of anaphylactic reaction to amphotericin B, Patients undergoing cord transplantation, Creatinine clearance < 60 ml/min, Patient with moderate or severe liver disease as defined by AST or ALT > 5 times the upper limit of normal (ULN), Patients who are unlikely to survive more than 1 month, Febrile patients (≥ 38.5°C), Patients who have received systemic antifungal therapy within 15 days prior to the inclusion, Any severe cardiovascular disease (such as arrhythmias, in particular) which may constitute a contra-indication to AmBisome® administration, Any severe disease other than the haematological diseases described in the second inclusion criteria, which in the investigator's judgement may interfere with study evaluations or affect the patient's safety, Pregnant or nursing females, Patients previously included in this study, Patients who have taken any investigational drug in the last 30 days prior to the inclusion.

Sites / Locations

  • Gilead Sciences

Outcomes

Primary Outcome Measures

The primary endpoint will be the safety defined by the incidence of adverse events occurring during the course of prophylaxis treatment (4 weeks for AL patients and 8 weeks for SCT patients).

Secondary Outcome Measures

The secondary endpoints for assessing efficacy will be the following:
Incidence of probable or proven invasive fungal infection according to EORTC-MSG 35 criteria within the12 weeks following the initiation of prophylaxis treatment.
Incidence of fever of unknown origin requiring empirical antifungal treatment within 12 weeks after trial initiation.
Incidence of superficial fungal infections within 3 months after trial initiation.
Time differential for commencement of empirical antifungal treatment measured within 3 months after trial initiation.
Evidence of colonisation by fungal organisms observed within 3 months after trial initiation.
Survival rate at the end of treatment and incidence of mortality related to fungal infection within 12 weeks and 24 weeks after study drug initiation.
Renal toxicity
The incidence and grade of nephrotoxicity will be assessed.
Hepatotoxicity
The incidence and grade hepatotoxicity will be assessed.
Patients whose AST or ALT becomes > 10 times the ULN will be withdrawn from the study.
Ionic analysis
Hypokalaemia: its incidence and grade will be evaluated. Potassium supplements received by the patient will be recorded in the Case Report Form.
Hypomagnesaemia: its incidence and grade will be evaluated as well.
Laboratories used by both sites will provide a list of their reference ranges.
Ionic disorders should be corrected throughout the trial.
Cardiovascular toxicity
The most commonly reported cardiovascular adverse events are rhythm disorders. There is a risk of seeing their incidence increase if the infusion is given too quickly.
Vital signs and ECG will be monitored throughout the trial.
Patients will be withdrawn from the trial, if in the investigator's opinion, further participation may put them at risk.
General safety
All adverse events occurring during the trial will be reported in the CRFs.

Full Information

First Posted
May 10, 2006
Last Updated
July 7, 2015
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT00362544
Brief Title
PROPHYSOME: Pilot Study on Safety of a Weekly Administration of 10mg/kg of AmBisome® in Antifungal Prophylaxis Treatment of Allogeneic Stem-cell Transplantation and Acute Leukaemia
Official Title
Pilot Study on Safety of a Weekly Administration of 10mg/kg of AmBisome® in Antifungal Prophylaxis Treatment of Allogeneic Stem-cell Transplantation and Acute Leukaemia
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2006 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Gilead Sciences

4. Oversight

5. Study Description

Brief Summary
This pilot study was designed in order to evaluate the safety and efficacy of an AmBisome loading dose regimen, in a weekly administration schedule, during the aplastic phase following induction or consolidation chemotherapy for acute leukaemia, and during the initial phase of allogeneic stem-cell transplant, which are both high risk periods as far as severe fungal infections development is concerned.
Detailed Description
This pilot study was designed in order to evaluate the safety and efficacy of an AmBisome loading dose regimen, in a weekly administration schedule, during the aplastic phase following induction or consolidation chemotherapy for acute leukaemia, and during the initial phase of allogeneic stem-cell transplant, which are both high risk periods as far as severe fungal infections development is concerned.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
antifungal prophylaxis, allogeneic stem-cell transplantation, acute leukaemia, antifungal prophylaxis treatment of allogeneic stem-cell transplantation and acute leukaemia

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Ambisome
Primary Outcome Measure Information:
Title
The primary endpoint will be the safety defined by the incidence of adverse events occurring during the course of prophylaxis treatment (4 weeks for AL patients and 8 weeks for SCT patients).
Secondary Outcome Measure Information:
Title
The secondary endpoints for assessing efficacy will be the following:
Title
Incidence of probable or proven invasive fungal infection according to EORTC-MSG 35 criteria within the12 weeks following the initiation of prophylaxis treatment.
Title
Incidence of fever of unknown origin requiring empirical antifungal treatment within 12 weeks after trial initiation.
Title
Incidence of superficial fungal infections within 3 months after trial initiation.
Title
Time differential for commencement of empirical antifungal treatment measured within 3 months after trial initiation.
Title
Evidence of colonisation by fungal organisms observed within 3 months after trial initiation.
Title
Survival rate at the end of treatment and incidence of mortality related to fungal infection within 12 weeks and 24 weeks after study drug initiation.
Title
Renal toxicity
Title
The incidence and grade of nephrotoxicity will be assessed.
Title
Hepatotoxicity
Title
The incidence and grade hepatotoxicity will be assessed.
Title
Patients whose AST or ALT becomes > 10 times the ULN will be withdrawn from the study.
Title
Ionic analysis
Title
Hypokalaemia: its incidence and grade will be evaluated. Potassium supplements received by the patient will be recorded in the Case Report Form.
Title
Hypomagnesaemia: its incidence and grade will be evaluated as well.
Title
Laboratories used by both sites will provide a list of their reference ranges.
Title
Ionic disorders should be corrected throughout the trial.
Title
Cardiovascular toxicity
Title
The most commonly reported cardiovascular adverse events are rhythm disorders. There is a risk of seeing their incidence increase if the infusion is given too quickly.
Title
Vital signs and ECG will be monitored throughout the trial.
Title
Patients will be withdrawn from the trial, if in the investigator's opinion, further participation may put them at risk.
Title
General safety
Title
All adverse events occurring during the trial will be reported in the CRFs.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients aged more than 18, Patients undergoing standard myelo-ablative, conditioning regimen and AGVHD ciclosporin prophylaxis for allogeneic stem cell transplantation, or Patients with acute leukaemia undergoing first induction therapy or second induction therapy after relapse, or consolidation therapy, Expected neutropenia < 0.5 giga/l for at least 2 weeks, Normal chest CT scan and/or normal X-ray of the chest at baseline, Patients with no sign or symptoms of fungal infection and no previous proven or probable IFI, Females of childbearing potential must be surgically incapable of pregnancy, or practising an acceptable method of birth control with a negative pregnancy test (blood or urine) at baseline, Understanding of the study and agreement of the patient to give written informed consent, Ability and agreement to comply with all study requirements, Patient willing to attend hospital appointments for each injection (infusions will be performed in hospital, under strict medical supervision). All patients will be hospitalised prior to, and remain in hospital for at least one day, after the first infusion. Exclusion Criteria: Known hypersensitivity to amphotericin B, in particular known history of anaphylactic reaction to amphotericin B, Patients undergoing cord transplantation, Creatinine clearance < 60 ml/min, Patient with moderate or severe liver disease as defined by AST or ALT > 5 times the upper limit of normal (ULN), Patients who are unlikely to survive more than 1 month, Febrile patients (≥ 38.5°C), Patients who have received systemic antifungal therapy within 15 days prior to the inclusion, Any severe cardiovascular disease (such as arrhythmias, in particular) which may constitute a contra-indication to AmBisome® administration, Any severe disease other than the haematological diseases described in the second inclusion criteria, which in the investigator's judgement may interfere with study evaluations or affect the patient's safety, Pregnant or nursing females, Patients previously included in this study, Patients who have taken any investigational drug in the last 30 days prior to the inclusion.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lamine Mahi, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Gilead Sciences
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

Learn more about this trial

PROPHYSOME: Pilot Study on Safety of a Weekly Administration of 10mg/kg of AmBisome® in Antifungal Prophylaxis Treatment of Allogeneic Stem-cell Transplantation and Acute Leukaemia

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