Clinical trial NCT00326157: PROPHESSOR: AmBisome in Antifungal Primary Prophylaxis Treatment of High Risk Patients Undergoing Allogeneic Stem Cell Transplantation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fungus Diseases
Keywords: antifungal primary prophylaxis treatment
allogeneic stem-cell transplantation
antifungal primary prophylaxis treatment of high risk patients undergoing allogeneic stem-cell transplantation
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2006-05-16
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability profile will be obtained by considering: Number (%) of patients with adverse events (AEs)
timeFrame: Through 16 weeks
measure: Number (%) of patients with infusion related AE
timeFrame: Through 16 weeks
measure: Laboratory parameters (in particular renal toxicity, hepatotoxicity, hypokalaemia, hypomagnesaemia)
timeFrame: Through 16 weeks
measure: Overall adverse events
timeFrame: Through 16 weeks
Secondary outcomes:
measure: 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
timeFrame: Within previous 6 months
measure: Number (%) of patients with fever of unknown origin requiring empirical antifungal treatment within the 6 months following the initiation of prophylaxis treatment
timeFrame: Within previous 6 months
measure: Number (%) of patients with superficial fungal infections within the 6 months following the initiation of prophylaxis treatment
timeFrame: Within previous 6 months
measure: Number (%) of patients with evidence of colonization by fungal organisms observed within the 6 months following the initiation of prophylaxis treatment
timeFrame: Within previous 6 months
measure: Reasons for early study discontinuation
timeFrame: Through 16 weeks
measure: 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
timeFrame: Within 12 months
measure: Time to probable or proven invasive fungal infection; fever of unknown origin requiring empirical antifungal treatment
timeFrame: Through 16 weeks
measure: Time to superficial fungal infections
timeFrame: Through 16 weeks
measure: Time to initiation of empirical antifungal treatment
timeFrame: Through 16 weeks
measure: Time to study discontinuation
timeFrame: Through 16 weeks
measure: Number of patients enrolled
timeFrame: Through 16 weeks
measure: Number of patients completing the study
timeFrame: Through 16 weeks
measure: Number of patients with early discontinuation
timeFrame: Through 16 weeks
measure: Number of patients classified by reason for discontinuing study drug (including the study completion)
timeFrame: Through 16 weeks
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Gilead Sciences
Study officials:
affiliation: Gilead Sciences
name: Luigi Picaro, MD
role: STUDY_DIRECTOR
References: