PROPHESSOR: AmBisome in Antifungal Primary Prophylaxis Treatment of High Risk Patients Undergoing Allogeneic Stem Cell Transplantation

Study Overview
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Brief Summary
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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 initial phase of allogeneic stem-cell transplant and in case of occurrence of graft versus host disease (GvHD), which are both high risk periods as far as severe fungal infection development is concerned.

Detailed Description
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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 initial phase of allogeneic stem-cell transplant and in case of occurrence of GvHD, which are both high risk periods as far as severe fungal infection development is concerned.

Official Title
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Phase II Pilot Study on Safety of Administration of 3mg/kg/Day Three Times a Week Until Day 22 (21 Days After Transplantation Day) and 7 mg/kg Weekly From Day 29 to the End of Treatment (Day 50-8th Week) of AmBisome® in Antifungal Primary Prophylaxis Treatment of High Risk Patients Undergoing Allogeneic Stem-cell Transplantation

Conditions
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Fungus Diseases

Intervention / Treatment
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* Drug: AmBisome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged more than 18 years Patients with hematological malignancies undergoing allogeneic stem cell transplantation from donors other than human leukocyte antigen (HLA) identical sibling; source of stem cell includes either peripheral blood or bone marrow No evidence of fungal infection at chest computed tomography (CT) scan and at sinus X-ray at baseline Patients with no sign or symptoms of fungal infection and no previous proven or probable invasive fungal infection (IFI) Females of childbearing potential must be surgically incapable of pregnancy, or practising a method of birth control, or agree to abstain from heterosexual intercourse while participating in the study, and with a negative pregnancy test (blood or urine) at baseline An 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 the hospital, under strict medical supervision). All patients will be hospitalised prior to, and remain in the 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 > 2.0 mg/dL 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 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 hematological diseases described at the second point of 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AmBisome® will be administered for a duration of 8 weeks | Drug: AmBisome<br>* 3mg/kg/day three times a week until day 22 (21 days after transplantation day) and 7 mg/kg weekly from day 29 to the end of treatment (day 50-8th Week) of AmBisome®, IV administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability profile will be obtained by considering: Number (%) of patients with adverse events (AEs) |  | Through 16 weeks | 
| Number (%) of patients with infusion related AE |  | Through 16 weeks | 
| Laboratory parameters (in particular renal toxicity, hepatotoxicity, hypokalaemia, hypomagnesaemia) |  | Through 16 weeks | 
| Overall adverse events |  | Through 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (%) of patients with probable or proven invasive fungal infection according to EORTC-MSG criteria within the 6 months following the initiation of prophylaxis treatment |  | Within previous 6 months | 
| Number (%) of patients with fever of unknown origin requiring empirical antifungal treatment within the 6 months following the initiation of prophylaxis treatment |  | Within previous 6 months | 
| Number (%) of patients with superficial fungal infections within the 6 months following the initiation of prophylaxis treatment |  | Within previous 6 months | 
| Number (%) of patients with evidence of colonization by fungal organisms observed within the 6 months following the initiation of prophylaxis treatment |  | Within previous 6 months | 
| Reasons for early study discontinuation |  | Through 16 weeks | 
| Survival rate and incidence of mortality related to fungal infection at the end of treatment and within 3, 6, and 12 months after the initiation of prophylaxis treatment |  | Within 12 months | 
| Time to probable or proven invasive fungal infection; fever of unknown origin requiring empirical antifungal treatment |  | Through 16 weeks | 
| Time to superficial fungal infections |  | Through 16 weeks | 
| Time to initiation of empirical antifungal treatment |  | Through 16 weeks | 
| Time to study discontinuation |  | Through 16 weeks | 
| Number of patients enrolled |  | Through 16 weeks | 
| Number of patients completing the study |  | Through 16 weeks | 
| Number of patients with early discontinuation |  | Through 16 weeks | 
| Number of patients classified by reason for discontinuing study drug (including the study completion) |  | Through 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antifungal primary prophylaxis treatment, allogeneic stem-cell transplantation, antifungal primary prophylaxis treatment of high risk patients undergoing allogeneic stem-cell transplantation