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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00362544
• Other study ID #: GS-FR-131-104
• Secondary ID: GS-FR-131-0119
• Status: Completed
• Phase: Phase 4
• First received: May 10, 2006
• Last updated: July 7, 2015
• Start date: October 2003
• Est. completion date: March 2006

Study information

• Verified date: July 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Leukemia

Intervention

Drug:
• Ambisome

Locations

Country	Name	City	State
France	Gilead Sciences	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

France, 

Outcome

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