Busulfan and Melphalan Conditioning in Multiple Myeloma

Summary

The purpose of this study is to determine whether intravenous busulfan and melphalan as a conditioning regimen is effective in the treatment of multiple myeloma undergoing autologous stem cell transplantation.

Timeline

Start

2013-01

Primary completion

2014-01

Completion

2015-12

Publications

• Background McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet. 1983 Oct 8;2(8354):822-4. doi: 10.1016/s0140-6736(83)90739-0.
• Background Selby PJ, McElwain TJ, Nandi AC, Perren TJ, Powles RL, Tillyer CR, Osborne RJ, Slevin ML, Malpas JS. Multiple myeloma treated with high dose intravenous melphalan. Br J Haematol. 1987 May;66(1):55-62. doi: 10.1111/j.1365-2141.1987.tb06890.x.
• Background Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, Fassas A, Zangari M, Hollmig K, Pineda-Roman M, Lee C, Talamo G, Thertulien R, Kiwan E, Krishna S, Fox M, Crowley J. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006 Mar 9;354(10):1021-30. doi: 10.1056/NEJMoa053583.
• Background Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996 Jul 11;335(2):91-7. doi: 10.1056/NEJM199607113350204.
• Background Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, Macro M, Pertuiset E, Dreyfus F, Mariette X, Boccacio C, Brouet JC. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998 Nov 1;92(9):3131-6.
• Background Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875-83. doi: 10.1056/NEJMoa022340.
• Background Blade J, Rosinol L, Sureda A, Ribera JM, Diaz-Mediavilla J, Garcia-Larana J, Mateos MV, Palomera L, Fernandez-Calvo J, Marti JM, Giraldo P, Carbonell F, Callis M, Trujillo J, Gardella S, Moro MJ, Barez A, Soler A, Font L, Fontanillas M, San Miguel J; Programa para el Estudio de la Terapeutica en Hemopatia Maligna (PETHEMA). High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood. 2005 Dec 1;106(12):3755-9. doi: 10.1182/blood-2005-03-1301. Epub 2005 Aug 16.
• Background Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M, Arnulf B, Royer B, Mariette X, Pertuiset E, Belanger C, Janvier M, Chevret S, Brouet JC, Ravaud P; Group Myelome-Autogreffe. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005 Dec 20;23(36):9227-33. doi: 10.1200/JCO.2005.03.0551. Epub 2005 Nov 7.
• Background Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD, McCoy J, Moore DF Jr, Dakhil SR, Lanier KS, Chapman RA, Cromer JN, Salmon SE, Durie B, Crowley JC. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol. 2006 Feb 20;24(6):929-36. doi: 10.1200/JCO.2005.04.5807. Epub 2006 Jan 23.
• Background Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. doi: 10.1002/ajh.2830330203.
• Background Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, Tricot G, Munshi N, Fassas A, Singhal S, Mehta J, Anaissie E, Dhodapkar D, Naucke S, Cromer J, Sawyer J, Epstein J, Spoon D, Ayers D, Cheson B, Crowley J. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood. 1999 Jan 1;93(1):55-65.
• Background Samson D, Gaminara E, Newland A, Van de Pette J, Kearney J, McCarthy D, Joyner M, Aston L, Mitchell T, Hamon M, et al. Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma. Lancet. 1989 Oct 14;2(8668):882-5. doi: 10.1016/s0140-6736(89)91549-3.
• Background Sirohi B, Powles R, Mehta J, Raje N, Kulkarni S, Ramiah V, Saso R, Horton C, Bhagwati N, Singhal S, Treleaven J. Complete remission rate and outcome after intensive treatment of 177 patients under 75 years of age with IgG myeloma defining a circumscribed disease entity with a new staging system. Br J Haematol. 1999 Dec;107(3):656-66. doi: 10.1046/j.1365-2141.1999.01744.x.
• Background Goldschmidt H, Hegenbart U, Wallmeier M, Hohaus S, Haas R. Factors influencing collection of peripheral blood progenitor cells following high-dose cyclophosphamide and granulocyte colony-stimulating factor in patients with multiple myeloma. Br J Haematol. 1997 Sep;98(3):736-44. doi: 10.1046/j.1365-2141.1997.2783095.x.
• Background Barlogie B, Alexanian R, Dicke KA, Zagars G, Spitzer G, Jagannath S, Horwitz L. High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma. Blood. 1987 Sep;70(3):869-72.
• Background Jagannath S, Vesole DH, Glenn L, Crowley J, Barlogie B. Low-risk intensive therapy for multiple myeloma with combined autologous bone marrow and blood stem cell support. Blood. 1992 Oct 1;80(7):1666-72.
• Background Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ, Guilhot F, Marit G, Doyen C, Jaubert J, Fuzibet JG, Francois S, Benboubker L, Monconduit M, Voillat L, Macro M, Berthou C, Dorvaux V, Pignon B, Rio B, Matthes T, Casassus P, Caillot D, Najman N, Grosbois B, Bataille R, Harousseau JL; Intergroupe Francophone du Myelome. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood. 2002 Feb 1;99(3):731-5. doi: 10.1182/blood.v99.3.731.
• Background Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, Lamy T, Marit G, Maloisel F, Berthou C, Dib M, Caillot D, Deprijck B, Ketterer N, Harousseau JL, Sotto JJ, Moreau P. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006 May 1;107(9):3474-80. doi: 10.1182/blood-2005-09-3869. Epub 2006 Jan 5.
• Background Moreau P, Milpied N, Mahe B, Juge-Morineau N, Rapp MJ, Bataille R, Harousseau JL. Melphalan 220 mg/m2 followed by peripheral blood stem cell transplantation in 27 patients with advanced multiple myeloma. Bone Marrow Transplant. 1999 May;23(10):1003-6. doi: 10.1038/sj.bmt.1701763.
• Background Mansi J, da Costa F, Viner C, Judson I, Gore M, Cunningham D. High-dose busulfan in patients with myeloma. J Clin Oncol. 1992 Oct;10(10):1569-73. doi: 10.1200/JCO.1992.10.10.1569.
• Background Bensinger WI, Rowley SD, Demirer T, Lilleby K, Schiffman K, Clift RA, Appelbaum FR, Fefer A, Barnett T, Storb R, Chauncey T, Maziarz RT, Klarnet J, McSweeney P, Holmberg L, Maloney DG, Weaver CH, Buckner CD. High-dose therapy followed by autologous hematopoietic stem-cell infusion for patients with multiple myeloma. J Clin Oncol. 1996 May;14(5):1447-56. doi: 10.1200/JCO.1996.14.5.1447.
• Background Alegre A, Lamana M, Arranz R, Fernandez-Villalta MJ, Tomas JF, Figuera A, Camara R, Steegman JL, Casado F, Requena MJ, et al. Busulfan and melphalan as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma. Br J Haematol. 1995 Oct;91(2):380-6. doi: 10.1111/j.1365-2141.1995.tb05307.x.
• Background Fermand JP, Chevret S, Ravaud P, Divine M, Leblond V, Dreyfus F, Mariette X, Brouet JC. High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients. Blood. 1993 Oct 1;82(7):2005-9.
• Background Ventura GJ, Barlogie B, Hester JP, Yau JC, LeMaistre CF, Wallerstein RO, Spinolo JA, Dicke KA, Horwitz LH, Alexanian R. High dose cyclophosphamide, BCNU and VP-16 with autologous blood stem cell support for refractory multiple myeloma. Bone Marrow Transplant. 1990 Apr;5(4):265-8.
• Background Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pegourie B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myelome (IFM). Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. doi: 10.1182/blood-2009-06-229658. Epub 2009 Nov 2.
• Background Lahuerta JJ, Grande C, Blade J, Martinez-Lopez J, de la Serna J, Alegre A, Garcia LJ, Caballero D, de la Rubia J, Marin J, Perez-Lopez C, Sureda A, Escudero A, Cabrera R, Conde E, Garcia-Ruiz JC, Perez-Equiza K, Hernandez F, Palomera L, Leon A, Giraldo P, Solano C, Bargay J, San MJ; Spanish Multiple Myeloma Group. Myeloablative treatments for multiple myeloma: update of a comparative study of different regimens used in patients from the Spanish registry for transplantation in multiple myeloma. Leuk Lymphoma. 2002 Jan;43(1):67-74. doi: 10.1080/10428190210194.
• Background Lahuerta JJ, Martinez-Lopez J, Grande C, Blade J, de la Serna J, Alegre A, Garcia-Larana J, Caballero D, Sureda A, de la Rubia J, Alvarez AM, Marin J, Escudero A, Conde E, Perez-Equiza K, Garcia Ruiz JC, Moraleda JM, Leon A, Bargay J, Cabrera R, Hernandez-Garcia MT, Diaz-Mediavilla J, Miguel JS. Conditioning regimens in autologous stem cell transplantation for multiple myeloma: a comparative study of efficacy and toxicity from the Spanish Registry for Transplantation in Multiple Myeloma. Br J Haematol. 2000 Apr;109(1):138-47. doi: 10.1046/j.1365-2141.2000.01979.x.
• Background Carreras E, Rosinol L, Terol MJ, Alegre A, de Arriba F, Garcia-Larana J, Bello JL, Garcia R, Leon A, Martinez R, Penarrubia MJ, Poderos C, Ribas P, Ribera JM, San Miguel J, Blade J, Lahuerta JJ; Spanish Myeloma Group/PETHEMA. Veno-occlusive disease of the liver after high-dose cytoreductive therapy with busulfan and melphalan for autologous blood stem cell transplantation in multiple myeloma patients. Biol Blood Marrow Transplant. 2007 Dec;13(12):1448-54. doi: 10.1016/j.bbmt.2007.08.002.
• Background Lahuerta JJ, Mateos MV, Martinez-Lopez J, Grande C, de la Rubia J, Rosinol L, Sureda A, Garcia-Larana J, Diaz-Mediavilla J, Hernandez-Garcia MT, Carrera D, Besalduch J, de Arriba F, Oriol A, Escoda L, Garcia-Frade J, Rivas-Gonzalez C, Alegre A, Blade J, San Miguel JF; Grupo Espanol de MM and Programa para el Estudio de la Terapeutica en Hemopatia Maligna Cooperative Study Groups. Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study. Haematologica. 2010 Nov;95(11):1913-20. doi: 10.3324/haematol.2010.028027. Epub 2010 Jul 27.
• Background McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M, Hardin BJ, Shulman HM, Clift RA. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med. 1993 Feb 15;118(4):255-67. doi: 10.7326/0003-4819-118-4-199302150-00003.
• Background Jones RJ, Lee KS, Beschorner WE, Vogel VG, Grochow LB, Braine HG, Vogelsang GB, Sensenbrenner LL, Santos GW, Saral R. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation. 1987 Dec;44(6):778-83. doi: 10.1097/00007890-198712000-00011.
• Jung SH, Lee JJ, Kim JS, Min CK, Kim K, Choi Y, Eom HS, Joo YD, Kim SH, Kwak JY, Kang HJ, Lee JH, Lee HS, Mun YC, Moon JH, Sohn SK, Park SK, Park Y, Shin HJ, Yoon SS; Korean Multiple Myeloma Working Party. Phase 2 Study of an Intravenous Busulfan and Melphalan Conditioning Regimen for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma (KMM150). Biol Blood Marrow Transplant. 2018 May;24(5):923-929. doi: 10.1016/j.bbmt.2018.01.004. Epub 2018 Jan 12.

Drugs

Indications