Febrile NeutropeniaPhase 4NCT00421187
Ambisome and Management of Culture-negative Neutropenic Fever Unresponsive to Antibiotics
A Phase 4 study testing Liposomal amphotericin B (AmBisome®) in people with Febrile Neutropenia, run by Gilead Sciences at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Febrile Neutropenia
- What is being tested?
- Liposomal amphotericin B (AmBisome®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteGreece
- Study dates
- Mar 2007to May 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Febrile Neutropenia
- Being tested
- Liposomal amphotericin B (AmBisome®)
- Keywords
- Antibiotic resistant neutropenic fever, ARNF, Ambisome, Liposomal amphotericin B
- Medical subject headings
- Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal amphotericin B (AmBisome®)Drug
Liposomal amphotericin B (AmBisome®)Drug
Also called Ambisome
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | AmBisome® will be given on day 0 (10 mg/kg), day 2 (5 mg/kg), and day 5 (5 mg/kg) Receives: 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 Receives: Drug: Liposomal amphotericin B (AmBisome®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK Profile of the dosing regimen under study (AUC, Cmax, Cmin, and etc.)
Measured: throughout
Secondary outcomes (8)
Proportion of patients with defervescence (temperature < 38°C for ≥ 48 hours) occurring during neutropenia
Measured: throughout
Time to defervescence from start of study entry and from time fever first recorded
Measured: throughout
Proportion of patients with emergence of an IFI during AmBisome® treatment
Measured: throughout
Survival during hospital admission
Measured: throughout
Survival at 14 days after study initiation
Measured: Day 14
Proportion of patients with treatment-emergent adverse events
Measured: throughout
Proportion of patients with treatment-emergent adverse events related to study drug
Measured: throughout
Proportion of patients with post-baseline toxicity grading changes in each laboratory test (those graded according to the protocol).
Measured: throughout
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2007 (estimated)
- Study startMar 2007
- Primary completionApr 2008
- Study completionMay 2008
Why it stopped: Unable to recruit subjects in the Turkey site.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Febrile NeutropeniaStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Lazaros Poughias, MD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00421187
- Sponsor's protocol ID
- GS-MM-131-0162
- Status last verified
- Apr 2008
- First submitted
- 8 Jan 2007
- Last updated
- 11 Mar 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00421187
- Acronym / sponsor ID
- GS-MM-131-0162
- Conditions
- Febrile Neutropenia
- Keywords
- Antibiotic resistant neutropenic fever, ARNF, Ambisome, Liposomal amphotericin B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to recruit subjects in the Turkey site.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Mar 2007
- Primary completion
- Apr 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 11 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Liposomal amphotericin B (AmBisome®)AmBisome® will be given on day 0 (10 mg/kg), day 2 (5 mg/kg), and day 5 (5 mg/kg) |
| 2 | Active comparator | Drug: Liposomal amphotericin B (AmBisome®)AmBisome as a constant daily dose of 3 mg/kg for a maximum of 14 days or until the resolution of fever and neutropenia |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
Key exclusion criteria (11 listed)
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal amphotericin B (AmBisome®) | Drug | 1 |
| Liposomal amphotericin B (AmBisome®)Also: Ambisome | Drug | 2 |
Primary outcome
PK Profile of the dosing regimen under study (AUC, Cmax, Cmin, and etc.)
Time frame: throughout
8 secondary outcomes
Proportion of patients with defervescence (temperature < 38°C for ≥ 48 hours) occurring during neutropenia
Time frame: throughout
Time to defervescence from start of study entry and from time fever first recorded
Time frame: throughout
Proportion of patients with emergence of an IFI during AmBisome® treatment
Time frame: throughout
Survival during hospital admission
Time frame: throughout
Survival at 14 days after study initiation
Time frame: Day 14
Proportion of patients with treatment-emergent adverse events
Time frame: throughout
Proportion of patients with treatment-emergent adverse events related to study drug
Time frame: throughout
Proportion of patients with post-baseline toxicity grading changes in each laboratory test (those graded according to the protocol).
Time frame: throughout
Results and safety
The study was stopped early (reason given: Unable to recruit subjects in the Turkey site.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lazaros Poughias, MD study director
Gilead Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liposomal amphotericin B (AmBisome®) in people with Febrile Neutropenia, run by Gilead Sciences at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Unable to recruit subjects in the Turkey site.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK Profile of the dosing regimen under study (AUC, Cmax, Cmin, and etc.) (time frame: throughout). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2011.