Nebulized Liposomal Amphotericin B Ambisome for Prophylaxis of Invasive Pulmonary Aspergillosis

Summary

The trial is planned as a multicentric, national, phase II, open-label trial to evaluate safety and tolerance of nebulized Liposomal Amphotericin B (Ambisome) for LMA patients during the induction therapy ,intensification, plus Allogeneic Haematopoietic Progenitor Cell transplant in due course, as well for patients diagnosed of several malignant haematologic diseases and treated with Allogeneic Haematopoietic Progenitor Cell Transplant

Timeline

Start

2006-01

Primary completion

2008-12

Completion

2009-04

Publications

• Background Denning DW. Invasive aspergillosis. Clin Infect Dis. 1998 Apr;26(4):781-803; quiz 804-5. doi: 10.1086/513943. No abstract available.
• Background Marr KA, Carter RA, Boeckh M, Martin P, Corey L. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood. 2002 Dec 15;100(13):4358-66. doi: 10.1182/blood-2002-05-1496. Epub 2002 Aug 22.
• Background Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Blumer JL, Leitz GJ, Territo MC. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med. 2003 May 6;138(9):705-13. doi: 10.7326/0003-4819-138-9-200305060-00006.
• Background Siwek GT, Dodgson KJ, de Magalhaes-Silverman M, Bartelt LA, Kilborn SB, Hoth PL, Diekema DJ, Pfaller MA. Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis. 2004 Aug 15;39(4):584-7. doi: 10.1086/422723. Epub 2004 Jul 30.
• Background Kramer MR, Denning DW, Marshall SE, Ross DJ, Berry G, Lewiston NJ, Stevens DA, Theodore J. Ulcerative tracheobronchitis after lung transplantation. A new form of invasive aspergillosis. Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):552-6. doi: 10.1164/ajrccm/144.3_Pt_1.552.
• Background Yeldandi V, Laghi F, McCabe MA, Larson R, O'Keefe P, Husain A, Montoya A, Garrity ER Jr. Aspergillus and lung transplantation. J Heart Lung Transplant. 1995 Sep-Oct;14(5):883-90.
• Background Westney GE, Kesten S, De Hoyos A, Chapparro C, Winton T, Maurer JR. Aspergillus infection in single and double lung transplant recipients. Transplantation. 1996 Mar 27;61(6):915-9. doi: 10.1097/00007890-199603270-00013.
• Background Cahill BC, Hibbs JR, Savik K, Juni BA, Dosland BM, Edin-Stibbe C, Hertz MI. Aspergillus airway colonization and invasive disease after lung transplantation. Chest. 1997 Nov 5;112(5):1160-4. doi: 10.1378/chest.112.5.1160.
• Background Reichenspurner H, Gamberg P, Nitschke M, Valantine H, Hunt S, Oyer PE, Reitz BA. Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis. Transplant Proc. 1997 Feb-Mar;29(1-2):627-8. doi: 10.1016/s0041-1345(96)00363-6. No abstract available.
• Background Calvo V, Borro JM, Morales P, Morcillo A, Vicente R, Tarrazona V, Paris F. Antifungal prophylaxis during the early postoperative period of lung transplantation. Valencia Lung Transplant Group. Chest. 1999 May;115(5):1301-4. doi: 10.1378/chest.115.5.1301.
• Background Dubois J, Bartter T, Gryn J, Pratter MR. The physiologic effects of inhaled amphotericin B. Chest. 1995 Sep;108(3):750-3. doi: 10.1378/chest.108.3.750.
• Background Schmitt HJ, Bernard EM, Hauser M, Armstrong D. Aerosol amphotericin B is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother. 1988 Nov;32(11):1676-9. doi: 10.1128/AAC.32.11.1676.
• Background Monforte V, Roman A, Gavalda J, Bravo C, Tenorio L, Ferrer A, Maestre J, Morell F. Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. J Heart Lung Transplant. 2001 Dec;20(12):1274-81. doi: 10.1016/s1053-2498(01)00364-3.
• Background Monforte V, Roman A, Gavalda J, Lopez R, Pou L, Simo M, Aguade S, Soriano B, Bravo C, Morell F. Nebulized amphotericin B concentration and distribution in the respiratory tract of lung-transplanted patients. Transplantation. 2003 May 15;75(9):1571-4. doi: 10.1097/01.TP.0000054233.60100.7A.
• Background Lambros MP, Bourne DW, Abbas SA, Johnson DL. Disposition of aerosolized liposomal amphotericin B. J Pharm Sci. 1997 Sep;86(9):1066-9. doi: 10.1021/js9604218.
• Background Thomas DA, Myers MA, Wichert B, Schreier H, Gonzalez-Rothi RJ. Acute effects of liposome aerosol inhalation on pulmonary function in healthy human volunteers. Chest. 1991 May;99(5):1268-70. doi: 10.1378/chest.99.5.1268.
• Background Kume H, Yamazaki T, Abe M, Tanuma H, Okudaira M, Okayasu I. Increase in aspergillosis and severe mycotic infection in patients with leukemia and MDS: comparison of the data from the Annual of the Pathological Autopsy Cases in Japan in 1989, 1993 and 1997. Pathol Int. 2003 Nov;53(11):744-50. doi: 10.1046/j.1440-1827.2003.01548.x.
• Background Nosari A, Oreste P, Cairoli R, Montillo M, Carrafiello G, Astolfi A, Muti G, Marbello L, Tedeschi A, Magliano E, Morra E. Invasive aspergillosis in haematological malignancies: clinical findings and management for intensive chemotherapy completion. Am J Hematol. 2001 Dec;68(4):231-6. doi: 10.1002/ajh.1187.
• Background Behre GF, Schwartz S, Lenz K, Ludwig WD, Wandt H, Schilling E, Heinemann V, Link H, Trittin A, Boenisch O, et al. Aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in neutropenic cancer patients. Ann Hematol. 1995 Dec;71(6):287-91. doi: 10.1007/BF01697981.
• Background Schwartz S, Behre G, Heinemann V, Wandt H, Schilling E, Arning M, Trittin A, Kern WV, Boenisch O, Bosse D, Lenz K, Ludwig WD, Hiddemann W, Siegert W, Beyer J. Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial. Blood. 1999 Jun 1;93(11):3654-61.
• Background Conneally E, Cafferkey MT, Daly PA, Keane CT, McCann SR. Nebulized amphotericin B as prophylaxis against invasive aspergillosis in granulocytopenic patients. Bone Marrow Transplant. 1990 Jun;5(6):403-6.
• Background Myers SE, Devine SM, Topper RL, Ondrey M, Chandler C, O'Toole K, Williams SF, Larson RA, Geller RB. A pilot study of prophylactic aerosolized amphotericin B in patients at risk for prolonged neutropenia. Leuk Lymphoma. 1992 Oct;8(3):229-33. doi: 10.3109/10428199209054909.
• Background Erjavec Z, Woolthuis GM, de Vries-Hospers HG, Sluiter WJ, Daenen SM, de Pauw B, Halie MR. Tolerance and efficacy of Amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in haematological patients. Eur J Clin Microbiol Infect Dis. 1997 May;16(5):364-8. doi: 10.1007/BF01726364.
• Background Hertenstein B, Kern WV, Schmeiser T, Stefanic M, Bunjes D, Wiesneth M, Novotny J, Heimpel H, Arnold R. Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia. Ann Hematol. 1994 Jan;68(1):21-6. doi: 10.1007/BF01695915.

Drugs

Indications