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

Fungus Diseases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00326157
• Other study ID #: GS-IT-131-0151
• Status: Completed
• Phase: Phase 2
• First received: May 10, 2006
• Last updated: February 11, 2010
• Start date: June 2006
• Est. completion date: November 2009

Study information

• Verified date: February 2010
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: November 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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

• Fungus Diseases
• Mycoses

Intervention

Drug:
• AmBisome
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

Locations

Country	Name	City	State
Italy	Gilead Sciences	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability profile will be obtained by considering: Number (%) of patients with adverse events (AEs)		Through 16 weeks	No
Primary	Number (%) of patients with infusion related AE		Through 16 weeks	No
Primary	Laboratory parameters (in particular renal toxicity, hepatotoxicity, hypokalaemia, hypomagnesaemia)		Through 16 weeks	No
Primary	Overall adverse events		Through 16 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	Number (%) of patients with superficial fungal infections within the 6 months following the initiation of prophylaxis treatment		Within previous 6 months	No
Secondary	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	No
Secondary	Reasons for early study discontinuation		Through 16 weeks	No
Secondary	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	No
Secondary	Time to probable or proven invasive fungal infection; fever of unknown origin requiring empirical antifungal treatment		Through 16 weeks	No
Secondary	Time to superficial fungal infections		Through 16 weeks	No
Secondary	Time to initiation of empirical antifungal treatment		Through 16 weeks	No
Secondary	Time to study discontinuation		Through 16 weeks	No
Secondary	Number of patients enrolled		Through 16 weeks	No
Secondary	Number of patients completing the study		Through 16 weeks	No
Secondary	Number of patients with early discontinuation		Through 16 weeks	No
Secondary	Number of patients classified by reason for discontinuing study drug (including the study completion)		Through 16 weeks	No