Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia
Condition: Invasive Fungal Disease
MeSH terms: Infections; Mycoses; Invasive Fungal Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Liposomal amphotericin B; Placebo
Intervention description: 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; 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
Intervention MeSH terms: Amphotericin B; Liposomal amphotericin B
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 355.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ambisome; ALL; invasive fungal infection; prophylaxis; liposomal amphotericin B; Invasive fungal infection prophylaxis

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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

          -  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.