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 - Full Text View

Sponsor:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00362544

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: Ambisome	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: Fungal Infections Leukemia Molds

Drug Information available for: Amphotericin B

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

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.

Estimated Enrollment:	30
Study Start Date:	October 2003
Estimated Study Completion Date:	March 2006

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00362544

Locations

France
Gilead Sciences
Paris, France, 75015

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Lamine Mahi, MD

Gilead Sciences

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00362544 History of Changes
Other Study ID Numbers:	GS-FR-131-104, GS-FR-131-0119
Study First Received:	May 10, 2006
Last Updated:	October 6, 2006
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Gilead Sciences:

antifungal prophylaxis
allogeneic stem-cell transplantation
acute leukaemia
antifungal prophylaxis treatment of allogeneic stem-cell transplantation and acute leukaemia

Additional relevant MeSH terms:

Leukemia
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Amphotericin B
Liposomal amphotericin B

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

ClinicalTrials.gov processed this record on February 09, 2012