Invasive Fungal DiseasePhase 3AmBiGuardNCT01259713
Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia
A Phase 3 study testing Liposomal amphotericin B in people with Invasive Fungal Disease, run by Gilead Sciences at 1 site in United Kingdom.
Trial summary
The study aims to investigate whether prophylaxis with liposomal amphotericin B (AmBisome®) can reduce the incidence of invasive fungal infections (IFIs) in patients with Acute Lymphoblastic Leukemia (ALL) who are undergoing their first remission induction. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Fungal Disease
- What is being tested?
- Liposomal amphotericin B
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 355 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2011to Jan 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Newly diagnosed ALL receiving an ALL chemotherapy regimen that typically induces at least 10 days of neutropenia defined as an absolute neutrophil count < 500 cells/mm^3 or 0.5 × 10^9 cells/L
- Subjects with lymphoblastic lymphoma or any malignancy other than ALL are NOT eligible for this study.
- Age ≥ 18 years
- Able to have all screening tests performed quickly to ensure results can be obtained and evaluated before randomization so that the first dose of randomized study drug for IFI prophylaxis can be administered within 5 days of first remission-induction chemotherapy
- Preremission induction treatment (ie, pre-phase) with a minimally or nonmyelosuppressive regimen for up to one week is not considered to constitute the beginning of remission induction chemotherapy
- Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures
Who cannot join
- Known hypersensitivity to amphotericin B or AmBisome, the metabolites or formulation excipients, in particular known history of anaphylactic reaction to amphotericin B or AmBisome or any of its metabolites or formulation excipients
- Known hypersensitivity to the excipients of the placebo formulation
- Current fever (≥ 38°C) unless explained by noninfectious causes
- Subjects with proven, probable or possible IFI (according to European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria) at screening or in subject history
- Pulmonary infiltrates
- Concomitant or previous treatment with an antifungal drug within the previous 30 days unless the plasma level is below the limit of detection or at least 5 half-lives of the antifungal has elapsed since the treatment was given
Show all 12Show fewer
- Serum creatinine > 2 × the upper limit of the normal range (ULN)
- Grade 3 Liver function test results: alanine aminotransferase or aspartate aminotransferase > 5 × ULN; total bilirubin > 2.5 x ULN
- Any severe co morbidity other than underlying hematological disease (ALL), which in the investigator's judgment may interfere with study evaluations or affect the subject's safety
- Subjects who have taken any investigational drug in the last 30 days prior to screening, with the exception of ALL chemotherapy investigational products being used as part of the subject's current ALL treatment protocol
- Pregnant or nursing females
- Subjects with a prior history of a malignancy that was treated with a myeloablative chemotherapy regimen are NOT eligible for this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of Prophylactic Liposomal Amphotericin B (AmBisome®) for the Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Remission-Induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)
The study aims to investigate whether prophylaxis with liposomal amphotericin B (AmBisome®) can reduce the incidence of invasive fungal infections (IFIs) in patients with Acute Lymphoblastic Leukemia (ALL) who are undergoing their first remission induction.
- Conditions
- Invasive Fungal Disease
- Being tested
- Liposomal amphotericin B, Placebo
- Keywords
- Ambisome, ALL, invasive fungal infection, prophylaxis, liposomal amphotericin B, Invasive fungal infection prophylaxis
- Medical subject headings
- Invasive Fungal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal amphotericin BDrug
Also called AmBisome
Ambisome 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week during induction chemotherapy
PlaceboDrug
Placebo to match liposomal amphotericin B administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Liposomal amphotericin B | Experimental | Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy Receives: Drug: Liposomal amphotericin B |
| Placebo | Placebo comparator | Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Proven or Probable IFIs During Remission-induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)
Diagnoses of proven or probable invasive fungal infections (IFI) were assessed according to European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria by the independent data review board (IDRB) who were blinded to treatment assignment.
The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.
Measured: During remission-induction chemotherapy (average 7 weeks)
Secondary outcomes (8)
Percentage of Participants With Pulmonary Infiltrates According to the Central Image Reader
Measured: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Diagnosed With Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the Investigator
Measured: During remission-induction chemotherapy (average 7 weeks)
Time to Diagnosis of Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the IDRB.
Time to diagnosis of proven or probable IFIs is presented as the median (Q1,Q3) days to diagnosis of those participants who experienced a proven or probable IFI. Median was not reached if < 50% of participants had an event; Q1 was not reached if < 25% of participants had an event; Q3 was not reached if < 75% of participants had an event.
Measured: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Requiring Antifungal Treatment During Remission-Induction Chemotherapy
Measured: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the IDRB.
Measured: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the Investigator.
Measured: During remission-induction chemotherapy (average 7 weeks)
Time From Beginning of Remission-induction Chemotherapy Until the Beginning of Consolidation Therapy
This endpoint was to evaluate the potential impact of IFI prevention on the efficacy of remission-induction chemotherapy for ALL.
Measured: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants With Complete Remission at the End of Remission Induction
This endpoint was to evaluate the potential impact of IFI prevention on the efficacy of remission-induction chemotherapy for ALL.
Measured: During remission-induction chemotherapy (average 7 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2010 (estimated)
- Study startApr 2011
- Primary completionDec 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Invasive Fungal DiseaseStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 355 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mike Hawkins, MD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01259713
- Sponsor's protocol ID
- GS-EU-131-0247
- Other IDs
- 2010-019562-91
- Acronym
- AmBiGuard
- Status last verified
- Apr 2015
- First submitted
- 10 Dec 2010
- Last updated
- 7 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of Prophylactic Liposomal Amphotericin B (AmBisome®) for the Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Remission-Induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)
- ClinicalTrials.gov ID
- NCT01259713
- Acronym / sponsor ID
- AmBiGuard / GS-EU-131-0247
- Conditions
- Invasive Fungal Disease
- Keywords
- Ambisome, ALL, invasive fungal infection, prophylaxis, liposomal amphotericin B, Invasive fungal infection prophylaxis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 355 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Apr 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 14 Dec 2010 (estimated)
- Results
- Posted 6 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study aims to investigate whether prophylaxis with liposomal amphotericin B (AmBisome®) can reduce the incidence of invasive fungal infections (IFIs) in patients with Acute Lymphoblastic Leukemia (ALL) who are undergoing their first remission induction.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liposomal amphotericin B | Experimental | Drug: Liposomal amphotericin BLiposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Newly diagnosed ALL receiving an ALL chemotherapy regimen that typically induces at least 10 days of neutropenia defined as an absolute neutrophil count < 500 cells/mm^3 or 0.5 × 10^9 cells/L
- Age ≥ 18 years
- Able to have all screening tests performed quickly to ensure results can be obtained and evaluated before randomization so that the first dose of randomized study drug for IFI prophylaxis can be administered within 5 days of first remission-induction chemotherapy
- Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures
Key exclusion criteria (12 listed)
- Known hypersensitivity to amphotericin B or AmBisome, the metabolites or formulation excipients, in particular known history of anaphylactic reaction to amphotericin B or AmBisome or any of its metabolites or formulation excipients
- Known hypersensitivity to the excipients of the placebo formulation
- Current fever (≥ 38°C) unless explained by noninfectious causes
- Subjects with proven, probable or possible IFI (according to European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria) at screening or in subject history
- Pulmonary infiltrates
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 BAlso: AmBisomeAmbisome 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week during induction chemotherapy | Drug | Liposomal amphotericin B |
| PlaceboPlacebo to match liposomal amphotericin B administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy | Drug | Placebo |
Primary outcome
Percentage of Participants With Proven or Probable IFIs During Remission-induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)
Time frame: During remission-induction chemotherapy (average 7 weeks)
Diagnoses of proven or probable invasive fungal infections (IFI) were assessed according to European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria by the independent data review board (IDRB) who were blinded to treatment assignment. The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.
8 secondary outcomes
Percentage of Participants With Pulmonary Infiltrates According to the Central Image Reader
Time frame: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Diagnosed With Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the Investigator
Time frame: During remission-induction chemotherapy (average 7 weeks)
Time to Diagnosis of Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the IDRB.
Time frame: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Requiring Antifungal Treatment During Remission-Induction Chemotherapy
Time frame: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the IDRB.
Time frame: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the Investigator.
Time frame: During remission-induction chemotherapy (average 7 weeks)
Time From Beginning of Remission-induction Chemotherapy Until the Beginning of Consolidation Therapy
Time frame: During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants With Complete Remission at the End of Remission Induction
Time frame: During remission-induction chemotherapy (average 7 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Mike Hawkins, 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 3 study testing Liposomal amphotericin B in people with Invasive Fungal Disease, run by Gilead Sciences at 1 site in United Kingdom.
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 6 inclusion and 12 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: finished, as of the sponsor's last update on 7 May 2015. 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 United Kingdom. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants With Proven or Probable IFIs During Remission-induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL) (time frame: During remission-induction chemotherapy (average 7 weeks)). 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 7 May 2015.