Ambisome and Management of Culture-negative Neutropenic Fever Unresponsive to Antibiotics

NCT00421187 | Terminated Phase 4

• 1 other identifier: GS-MM-131-0162
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Administration of a single high dose (10 mg/kg) of AmBisome® no later than 72 hours after ARNF onset followed by two 5 mg/kg doses on days 2 and 5 may provide sustained tissue levels of amphotericin B that are as mycologically effective as those provided after administering the standard daily dose of 3 mg/kg/day. The new dosing regimen is anticipated to be equally clinically effective compared with the standard AmBisome® regimen when given for the duration of neutropenic fever in patients with ARNF. In addition, the degree and incidence of nephrotoxicity are predicted to be lower with the 3 sequential dose regimen compared to daily dosing with 3 mg/kg because of the lower cumulative dosage (20 mg/kg versus 42 mg/kg, respectively), which is 1 contributing factor for the development of acute renal failure. Furthermore, the lower cumulative dose may be a cost-effective strategy for the treatment of patients with ARNF.

Conditions

Febrile Neutropenia

Keywords

Antibiotic resistant neutropenic fever; ARNF; Ambisome; Liposomal amphotericin B

Outcome Measures

Primary Outcomes (1)

• PK Profile of the dosing regimen under study (AUC, Cmax, Cmin, and etc.)

  throughout

Secondary Outcomes (8)

• Proportion of patients with defervescence (temperature < 38°C for ≥ 48 hours) occurring during neutropenia

  throughout

• Time to defervescence from start of study entry and from time fever first recorded

  throughout

• Proportion of patients with emergence of an IFI during AmBisome® treatment

  throughout

• Survival during hospital admission

  throughout

• Survival at 14 days after study initiation

  Day 14

Study Arms (2)

1

EXPERIMENTAL

AmBisome® will be given on day 0 (10 mg/kg), day 2 (5 mg/kg), and day 5 (5 mg/kg)

Drug: Liposomal amphotericin B (AmBisome®)

2

ACTIVE COMPARATOR

AmBisome as a constant daily dose of 3 mg/kg for a maximum of 14 days or until the resolution of fever and neutropenia

Drug: Liposomal amphotericin B (AmBisome®)

Interventions

Liposomal amphotericin B (AmBisome®) DRUG

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• Age ≥ 18 years
• Neutropenia (\< 0.5 x 109 cells/L)
• Received empiric antibiotic treatment for 3 days for blood culture negative infection
• Persistent fever of ≥ 38°C
• No known IFI at baseline during this neutropenic episode. However, patients with "missed" evidence of IFI (features absent at randomization but evidence within 48 hours \[eg, positive chest computerized tomography (CT)\]) will complete the randomized treatment and kinetic measurements
• No antifungal prophylaxis or treatment in this hospital admission or for the past 30 days
• Baseline liver function tests ≤ 10 times the upper limit of normal and baseline creatinine ≤ 2 times the upper limit of normal
• No known hypersensitivity to amphotericin B or LAMB or any of its constituents, in particular known history of anaphylactic reaction to amphotericin B or LAMB or any of its constituents
• Females of childbearing potential (less than 2 years post menopausal) must be surgically incapable of pregnancy, or practicing an acceptable method of birth control with a negative pregnancy test (blood or urine) at baseline
• Ability to comply with all study requirements
• Written informed consent

You may not qualify if:

• Evidence of proven, probably or possible invasive fungal infection
• Chronic invasive fungal infection, defined as signs/symptoms of invasive fungal infection present for \>4 weeks preceding entry into study
• Prior systemic therapy greater or equal to 4 days with any polyene anti-fungal agent within 30 days of study enrollment
• Prior systemic therapy with non-polyenes (i.e., azole or echinochandin derivatives) for the current ARNF. (Prior systemic anti-fungal therapy with non-polyene derivatives for prophylaxis or as empiric therapy for febrile neutropenia is permissible.)
• Use of another investigational, unlicensed drug within 30 days of screening or concurrent participation in another clinical trial using an investigational, unlicensed drug.
• Serum creatinine \> 2x upper limit of normal (ULN)
• Serum ALT or AST \> 5x ULN
• History of allergy or serious adverse reaction to any polyene anti-fungal agent.
• Patients who have a positive blood culture within 5 days before day 0 with a clinically significant organism isolated from the peripheral blood, who despite appropriate antibiotics have persistent positive cultures
• Pregnant or lactating women.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Gilead Sciences

Athens, 167 77, Greece

Location

MeSH Terms

Conditions

Febrile Neutropenia

Interventions

liposomal amphotericin B

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Study Officials

• Lazaros Poughias, MD

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 8, 2007
• First Posted: January 11, 2007
• Study Start: March 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: May 1, 2008
• Last Updated: March 11, 2011

Record last verified: 2008-04

Locations

GR (1)