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

Conditions: Leukemia

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.

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 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 \ 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.

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