- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00421187
Ambisome and Management of Culture-negative Neutropenic Fever Unresponsive to Antibiotics
Phase III Study of 3 Sequential Doses (10 mg/kg, 5 mg/kg, and 5 mg/kg) vs 3 mg/kg/Day of AmBisome® in the Management of Culture-negative Neutropenic Fever Unresponsive to Antibiotics
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a phase III, multicenter, randomized, open-label study. One center in the United Arab Emirates and 1 center in Turkey will participate in this trial and approximately 50 patients will be recruited.
Patients will be adults with hematological malignancies undergoing chemotherapy for leukemia or lymphoma. These patients will be treated with AmBisome® until resolution of fever and neutropenia or for a maximum of 14 days.
Patients will be randomized to receive AmBisome 10 mg/kg on treatment day 0 followed by 5 mg/kg on days 2 and 5 or AmBisome 3 mg/kg/day for 14 days. Study medication will be administered during the period of ARNF until resolution of fever and neutropenia and/or a minimum of 14 days. At the end of the 14-day trial period, each patient will be classified as having responded or not responded to the treatment according to the criteria for response given below.
Patients will be examined daily for evidence of drug toxicity or intolerance and for the development of an IFI. Vital signs will be recorded every 6 hours if the patient is stable or more frequently if there is evidence of clinical deterioration. In the event of a clinical IFI (i.e., development of a halo sign or positive fungal blood cultures), the patient will be withdrawn from the study, classified as treatment failure, and receive antifungal treatment with either caspofungin or voriconazole. Daily clinical observations will ensure rapid detection of such an event in accordance with standard IDSA guidelines4. Patients who show clinical deterioration (i.e., increasing dyspnea, hypotension) but exhibit no definite evidence of an IFI may also be classified as treatment failures. Patients with evidence of biochemical and/or clinical drug toxicity will be withdrawn from the study and appropriate management will be given.
For patients who remain febrile after 14 days but who are otherwise stable and have no discernable cause for the fever, continuation of treatment with AmBisome 3 mg/kg/day or treatment with another antifungal drug treatment, antibiotic, or discontinuation of antimicrobial therapy will be undertaken at the discretion of the investigator. Patients who meet these criteria will have a thorough diagnostic evaluation to investigate the cause of their fever.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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-
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Athens, Greece, 167 77
- Gilead Sciences
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. Adult patients with hematologic malignancy undergoing chemotherapy for leukemia or lymphoma will be recruited into this study from 2 centers provided the following inclusion criteria are fulfilled:
- 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
Exclusion Criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 1
AmBisome® will be given on day 0 (10 mg/kg), day 2 (5 mg/kg), and day 5 (5 mg/kg)
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Other Names:
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ACTIVE_COMPARATOR: 2
AmBisome as a constant daily dose of 3 mg/kg for a maximum of 14 days or until the resolution of fever and neutropenia
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
PK Profile of the dosing regimen under study (AUC, Cmax, Cmin, and etc.)
Time Frame: throughout
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throughout
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of patients with defervescence (temperature < 38°C for ≥ 48 hours) occurring during neutropenia
Time Frame: throughout
|
throughout
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Time to defervescence from start of study entry and from time fever first recorded
Time Frame: throughout
|
throughout
|
Proportion of patients with emergence of an IFI during AmBisome® treatment
Time Frame: throughout
|
throughout
|
Survival during hospital admission
Time Frame: throughout
|
throughout
|
Survival at 14 days after study initiation
Time Frame: Day 14
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Day 14
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Proportion of patients with treatment-emergent adverse events
Time Frame: throughout
|
throughout
|
Proportion of patients with treatment-emergent adverse events related to study drug
Time Frame: throughout
|
throughout
|
Proportion of patients with post-baseline toxicity grading changes in each laboratory test (those graded according to the protocol).
Time Frame: throughout
|
throughout
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Lazaros Poughias, MD, Gilead Sciences
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GS-MM-131-0162
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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