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

Sponsored by:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00326157

Purpose

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.

Condition	Intervention	Phase
Fungus Diseases	Drug: AmBisome	Phase II

MedlinePlus related topics: Fungal Infections Molds

Drug Information available for: Amphotericin B Clotrimazole Miconazole Miconazole nitrate Tioconazole

U.S. FDA Resources

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

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Safety and tolerability profile will be obtained by considering: Number (%) of patients with adverse events (AEs) [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Number (%) of patients with infusion related AE [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Laboratory parameters (in particular renal toxicity, hepatotoxicity, hypokalaemia, hypomagnesaemia) [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Overall adverse events [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Time Frame: Within previous 6 months ] [ Designated as safety issue: No ]
Number (%) of patients with fever of unknown origin requiring empirical antifungal treatment within the 6 months following the initiation of prophylaxis treatment [ Time Frame: Within previous 6 months ] [ Designated as safety issue: No ]
Number (%) of patients with superficial fungal infections within the 6 months following the initiation of prophylaxis treatment [ Time Frame: Within previous 6 months ] [ Designated as safety issue: No ]
Number (%) of patients with evidence of colonization by fungal organisms observed within the 6 months following the initiation of prophylaxis treatment [ Time Frame: Within previous 6 months ] [ Designated as safety issue: No ]
Reasons for early study discontinuation [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
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 Frame: Within 12 months ] [ Designated as safety issue: No ]
Time to probable or proven invasive fungal infection; fever of unknown origin requiring empirical antifungal treatment [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Time to superficial fungal infections [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Time to initiation of empirical antifungal treatment [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Time to study discontinuation [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Number of patients enrolled [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Number of patients completing the study [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Number of patients with early discontinuation [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]
Number of patients classified by reason for discontinuing study drug (including the study completion) [ Time Frame: Through 16 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	June 2006
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental AmBisome® will be administered for a duration of 8 weeks	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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00326157

Contacts

Contact: Loredana Balzano

+39 02 43920239

RosariaLoredana.Balzano@gilead.com

Locations

Italy
Gilead Sciences	Recruiting
Milan, Italy, 20146

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Pier Luigi Carriero, MD

Gilead Sciences

More Information

Responsible Party:	Gilead Sciences ( Pier Luigi Carriero )
Study ID Numbers:	GS-IT-131-0151
Study First Received:	May 10, 2006
Last Updated:	November 11, 2008
ClinicalTrials.gov Identifier:	NCT00326157
Health Authority:	Italy: The Italian Medicines Agency

Keywords provided by Gilead Sciences:

antifungal primary prophylaxis treatment
allogeneic stem-cell transplantation
antifungal primary prophylaxis treatment of high risk patients undergoing allogeneic stem-cell transplantation

Study placed in the following topic categories:

Abelcet
Amphotericin B
Mycoses
Clotrimazole

Miconazole
Tioconazole
Liposomal amphotericin B

Additional relevant MeSH terms:

Anti-Infective Agents, Local
Anti-Bacterial Agents
Anti-Infective Agents
Antiparasitic Agents
Antiprotozoal Agents

Antifungal Agents
Therapeutic Uses
Antibiotics, Antifungal
Amebicides
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009