Study to investigate the ability of AmBisome to prevent the development of serious invasive infections caused by fungi in patients diagnosed with acute lymphoblastic leukemia receiving the initial phase of their chemotherapy treatment.
- Conditions
- Invasive fungal infections (IFI) in subjects with Acute Lymphoblastic Leukemia (ALL) undergoing remission induction chemotherapyMedDRA version: 14.1Level: PTClassification code 10017533Term: Fungal infectionSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2010-019562-91-BE
- Lead Sponsor
- Gilead Sciences International Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 354
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
•Newly diagnosed ALL receiving an ALL chemotherapy regimen that typically induces at least 10 days of neutropenia, defined as an absolute neutrophil count (ANC)<500 cells/mm3 or 0.5x109 cells/L.
Note: 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 no later than 5 days after the start of remission-induction chemotherapy
Note: with respect to this timing, pre-remission induction treatment (i.e. pre-phase) with a minimally or non-myelosuppressive 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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 344
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
•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 fungal causes have clearly been excluded, e.g. negative lung and sinus imaging, documented drug-fever, or response to anti-bacterial antibiotic treatment.
•Subjects with proven, probable or possible IFI (according to 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.
•Serum creatinine > 2 x the upper limit of the normal range (ULN)
•Grade 3 Liver function test results (prior to starting remission induction chemotherapy): alanine aminotransferase or aspartate aminotransferase > 5 x 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: •To determine the prophylactic efficacy of AmBisome compared to placebo in preventing IFIs in subjects with ALL undergoing remission induction chemotherapy.;Secondary Objective: •To determine the safety and tolerability of prophylactic AmBisome in subjects with ALL undergoing remission induction chemotherapy.<br>•To determine the impact of IFI prevention on the efficacy of remission induction chemotherapy in subjects with ALL.<br>;Primary end point(s): The primary objective of this study is to assess antifungal prophylaxis efficacy of AmBisome 5 mg/kg compared to placebo. <br>The primary efficacy endpoint in support of this objective is the proportion of subjects with proven or probable IFIs during remission induction chemotherapy for ALL. ;Timepoint(s) of evaluation of this end point: Interim analysis for efficacy when 50% of subjects have completed the study.<br>Final analysis when all subjects have completed the protocol defined last patient last visit.
- Secondary Outcome Measures
Name Time Method