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

Condition(s) targeted: Fungus Diseases

Intervention: AmBisome (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Gilead Sciences

Official(s) and/or principal investigator(s):
Pier Luigi Carriero, MD, Study Director, Affiliation: Gilead Sciences

Overall contact:
Loredana Balzano, Phone: +39 02 43920239, Email: RosariaLoredana.Balzano@gilead.com

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.

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 design: Prevention, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

Safety and tolerability profile will be obtained by considering: Number (%) of patients with adverse events (AEs)

Number (%) of patients with infusion related AE

Laboratory parameters (in particular renal toxicity, hepatotoxicity, hypokalaemia, hypomagnesaemia)

Overall adverse events

Secondary outcome:

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

Number (%) of patients with fever of unknown origin requiring empirical antifungal treatment within the 6 months following the initiation of prophylaxis treatment

Number (%) of patients with superficial fungal infections within the 6 months following the initiation of prophylaxis treatment

Number (%) of patients with evidence of colonization by fungal organisms observed within the 6 months following the initiation of prophylaxis treatment

Reasons for early study discontinuation

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

Time to probable or proven invasive fungal infection; fever of unknown origin requiring empirical antifungal treatment

Time to superficial fungal infections

Time to initiation of empirical antifungal treatment

Time to study discontinuation

Number of patients enrolled

Number of patients completing the study

Number of patients with early discontinuation

Number of patients classified by reason for discontinuing study drug (including the study completion)

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Loredana Balzano, Phone: +39 02 43920239, Email: RosariaLoredana.Balzano@gilead.com

Gilead Sciences, Milan 20146, Italy; Recruiting

Starting date: June 2006
Ending date: July 2009
Last updated: November 11, 2008