Anidulafungin in Patients With Hematologic Malignancies

Summary

Study objectives To evaluate the safety of the echinocandin anidulafungin for prophylaxis or treatment of invasive fungal infections (IFI) in hematologic patients. Study design, Study conduct period Prospective, open label, phase II, one arm, single centre study October 2009 - September 2010 Study population Twenty adult patients (≥ 18 years) with a hematologic disorder and an indication for antifungal prophylaxis or therapy, but a relative contraindication for azoles or polyenes due to hepatic and renal dysfunction respectively Methods and Main Out-come Variables Main Outcome Parameter Safety: Adverse events and changes of important laboratory parameters with clinical impact will be reported. Secondary Outcome Parameter Efficacy: In therapeutically use the outcome will be categorized into success or failure. For patients receiving anidulafungin as prophylaxis the number and rate of breakthrough infections will be documented. Risk assessment Treatment related adverse effects as reported in the approved physician prescribing information (usually mild and with an incidence of \< 5%). Treatment failure due to resistant pathogens. Expected benefit from this study IFI is a major cause of death among hematological patients, especially those undergoing high dose chemotherapy. It is conceivable that anidulafungin is a new treatment option for patients in whom azoles or polyenes are relatively contraindicated.

Timeline

Start

2009-10

Primary completion

2011-09

Completion

2011-09

Publications

• Background Damle BD, Dowell JA, Walsky RL, Weber GL, Stogniew M, Inskeep PB. In vitro and in vivo studies to characterize the clearance mechanism and potential cytochrome P450 interactions of anidulafungin. Antimicrob Agents Chemother. 2009 Mar;53(3):1149-56. doi: 10.1128/AAC.01279-08. Epub 2008 Nov 24.
• Background Krause DS, Reinhardt J, Vazquez JA, Reboli A, Goldstein BP, Wible M, Henkel T; Anidulafungin Invasive Candidiasis Study Group. Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia. Antimicrob Agents Chemother. 2004 Jun;48(6):2021-4. doi: 10.1128/AAC.48.6.2021-2024.2004.
• Background Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD; Infectious Diseases Society of America. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Mar 1;48(5):503-35. doi: 10.1086/596757.
• Background Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, Betts R, Wible M, Goldstein BP, Schranz J, Krause DS, Walsh TJ; Anidulafungin Study Group. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007 Jun 14;356(24):2472-82. doi: 10.1056/NEJMoa066906.
• Background De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Munoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. 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 Jun 15;46(12):1813-21. doi: 10.1086/588660.
• Background Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, Walsh TJ, Maertens J, Patterson TF, Perfect JR, Dupont B, Wingard JR, Calandra T, Kauffman CA, Graybill JR, Baden LR, Pappas PG, Bennett JE, Kontoyiannis DP, Cordonnier C, Viviani MA, Bille J, Almyroudis NG, Wheat LJ, Graninger W, Bow EJ, Holland SM, Kullberg BJ, Dismukes WE, De Pauw BE. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008 Sep 1;47(5):674-83. doi: 10.1086/590566.
• Background Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

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