Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2017 Aug 1;72(8):2359-2367.
doi: 10.1093/jac/dkx133.

Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia

Oliver A Cornely  1 , Thibaut Leguay  2 , Johan Maertens  3 , Maria J G T Vehreschild  4 , Achilles Anagnostopoulos  5 , Carlo Castagnola  6 , Luisa Verga  7 , Christina Rieger  8 , Mustafa Kondakci  9 , Georg Härter  10 , Rafael F Duarte  11 , Bernardino Allione  12 , Catherine Cordonnier  13 , Claus Peter Heussel  14 , C Orla Morrissey  15 , Samir G Agrawal  16 , J Peter Donnelly  17 , Mark Bresnik  18 , Michael J Hawkins  18 , Will Garner  18 , Nicola Gökbuget  19 ; AmBiGuard Study Group
Affiliations
Clinical Trial

Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia

Oliver A Cornely et al. J Antimicrob Chemother. .

Abstract

Objectives: To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL).

Patients and methods: In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB.

Results: Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB ( n = 237) or placebo ( n = 118). Rates of proven and probable IFD assessed independently were 7.9% (18/228) in the L-AMB group and 11.7% (13/111) in the placebo group ( P = 0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group ( P = 0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo ( P = 1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB.

Conclusions: The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7% in the placebo group, and was not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
CONSORT flow diagram. Of 360 subjects randomized, 5 were never dosed, and 16 (9 L-AMB, 7 placebo) were excluded from the efficacy analysis, 1 due to misdiagnosis (AML) and 15 due to protocol-prohibited antifungal treatment either concomitant with or within the previous 30 days.
Figure 2.
Figure 2.
Time to diagnosis of invasive fungal disease as assessed by the independent data review board.
See this image and copyright information in PMC

References

    1. Bassan R, Hoelzer D.. Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 2011; 29: 532–43. - PubMed
    1. Pagano L, Caira M, Candoni A. et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 2006; 91: 1068–75. - PubMed
    1. Teng JC, Slavin MA, Teh BW. et al. Epidemiology of invasive fungal disease in lymphoproliferative disorders. Haematologica 2015; 100: e462–6. - PMC - PubMed
    1. de Pauw B, Walsh TJ, Donnelly JP. et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813–21. - PMC - PubMed
    1. Rüping MJ, Vehreschild JJ, Cornely OA.. Patients at high risk of invasive fungal infections: when and how to treat. Drugs 2008; 68: 1941–62. - PubMed

Publication types

MeSH terms