GEM05 for Patients With Multiple Myeloma More Than 65 Years Old

Summary

The primary objective is to analyze and compare the efficacy, the response rate, the CR and the response rate duration of both induction treatments and both maintenance treatments

Timeline

Start

2005-03

Primary completion

2007-03

Completion

2009-12

Publications

• Background Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33. doi: 10.3322/canjclin.50.1.7.
• Background 2. Longo D. Plasma cell disorders. In : Fauce A, et al. Ed. Harrison's Principles of Internal Medicine. 14th Ed. New York, New York: Mc Graw-Hill; 1998: 712-718.
• Background Raje N, Anderson K. Thalidomide--a revival story. N Engl J Med. 1999 Nov 18;341(21):1606-9. doi: 10.1056/NEJM199911183412110. No abstract available.
• Background Holland JR, Hosley H, Scharlau C, Carbone PP, Frei E 3rd, Brindley CO, Hall TC, Shnider BI, Gold GL, Lasagna L, Owens AH Jr, Miller SP. A controlled trial of urethane treatment in multiple myeloma. Blood. 1966 Mar;27(3):328-42. No abstract available.
• Background Alexanian R, Haut A, Khan AU, Lane M, McKelvey EM, Migliore PJ, Stuckey WJ Jr, Wilson HE. Treatment for multiple myeloma. Combination chemotherapy with different melphalan dose regimens. JAMA. 1969 Jun 2;208(9):1680-5. doi: 10.1001/jama.208.9.1680. No abstract available.
• Background Salmon SE, Haut A, Bonnet JD, Amare M, Weick JK, Durie BG, Dixon DO. Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol. 1983 Aug;1(8):453-61. doi: 10.1200/JCO.1983.1.8.453.
• Background Boccadoro M, Marmont F, Tribalto M, Avvisati G, Andriani A, Barbui T, Cantonetti M, Carotenuto M, Comotti B, Dammacco F, et al. Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients. J Clin Oncol. 1991 Mar;9(3):444-8. doi: 10.1200/JCO.1991.9.3.444.
• Background MacLennan IC, Chapman C, Dunn J, Kelly K. Combined chemotherapy with ABCM versus melphalan for treatment of myelomatosis. The Medical Research Council Working Party for Leukaemia in Adults. Lancet. 1992 Jan 25;339(8787):200-5. doi: 10.1016/0140-6736(92)90004-m.
• Background Oken MM, Harrington DP, Abramson N, Kyle RA, Knospe W, Glick JH. Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of multiple myeloma: results of Eastern Cooperative Oncology Group Study E2479. Cancer. 1997 Apr 15;79(8):1561-7.
• Background Blade J, San Miguel JF, Alcala A, Maldonado J, Sanz MA, Garcia-Conde J, Moro MJ, Alonso C, Besalduch J, Zubizarreta A, et al. Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients. J Clin Oncol. 1993 Jun;11(6):1165-71. doi: 10.1200/JCO.1993.11.6.1165.
• Background Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists' Collaborative Group. J Clin Oncol. 1998 Dec;16(12):3832-42. doi: 10.1200/JCO.1998.16.12.3832.
• Background Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26;348(26):2609-17. doi: 10.1056/NEJMoa030288.
• Background Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004 Oct;127(2):165-72. doi: 10.1111/j.1365-2141.2004.05188.x.
• Background 14. Paul Richardson et al. Bortezomib Demonstrates Superior Efficacy to High-Dose Dexamethasone in Relapsed Multiple Myeloma: Final Report of the APEX Study. Blood 2004; 104(11):Abstract number 336.5
• Background Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, Kyle RA, Witzig TE. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol. 2002 Nov 1;20(21):4319-23. doi: 10.1200/JCO.2002.02.116.
• Background Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003 Jan 1;21(1):16-9. doi: 10.1200/JCO.2003.03.139.
• Background Rajkumar SV. Thalidomide in newly diagnosed multiple myeloma and overview of experience in smoldering/indolent disease. Semin Hematol. 2003 Oct;40(4 Suppl 4):17-22. doi: 10.1053/j.seminhematol.2003.09.007.
• Background 18. Antonio Palumbo, Alessandra Bertola, Pellegrino Musto, Tommaso Caravita, Vincenzo Callea, Clotilde Cangialosi, Anna Marina Liberati, Pasquale Niscola, Lucio Catalano, Mariella Grasso, Vito Michele Lauta, Maria Concetta Petti, Sergio Morandi, Monica Galli, Sara Bringhen, Federica Cavallo, Patrizia Falco, Mario Boccadoro. A Prospective Randomized Trial of Oral Melphalan, Prednisone, Thalidomide (MPT) vs Oral Melphalan, Prednisone (MP): An Interim Analysis. Blood 2004. Volume 104, issue 11.Abstract number 207
• Background 19. Maurizio Zangari, Bart Barlogie, Joth Jacobson, Erik Rasmussen, Michael Burns, Bob Kordsmeier, John D. Shaughnessy, Elias J. Anaissie, Raymond Thertulien, Athanasios Fassas, Choon-Kee Lee, David Schenkein, Jerome B. Zeldis, Guido Tricot. VTD Regimen Comprising Velcade (V) + Thalidomide (T) and Added DEX (D) for Non-Responders to V + T Effects a 57% PR Rate among 56 Patients with Myeloma (M) Relapsing after Autologous Transplant. Blood 2003, Volume 102, issue 11. Abstract number 830
• Background 20. Jagannath S, Brian D, Wolf j, Camacho E, Irwin D, Lutzky J, Mckinley M, Gabayan E, Mazumder A, Crowley K, Sckenkein D. A phase 2 study of Bortezomib as first-line therapy in patients with multiple myeloma. Blood 2004; 104(11). Abstract number 333
• Background 21. Alexanian R, Wang L, Weber D, Delasalle K. VTD (Velcade, Thalidomide, Dexamethasone) as primary therapy for newly-diagnosed multiple myeloma. Blood 2004; 104(11). Abstract number 210
• Background Mateos MV, Hernandez JM, Hernandez MT, Gutierrez NC, Palomera L, Fuertes M, Diaz-Mediavilla J, Lahuerta JJ, de la Rubia J, Terol MJ, Sureda A, Bargay J, Ribas P, de Arriba F, Alegre A, Oriol A, Carrera D, Garcia-Larana J, Garcia-Sanz R, Blade J, Prosper F, Mateo G, Esseltine DL, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood. 2006 Oct 1;108(7):2165-72. doi: 10.1182/blood-2006-04-019778. Epub 2006 Jun 13.
• Background Whealthy K (On behalf of the Myeloma Trialists'Collaborative Group). Which myeloma patients benefit from interferon therapy?. An overview of 24 randomised trials with 4,000 patients, Br J Haematol 1998; 102: 140
• Background Blade J, Esteve J. Viewpoint on the impact of interferon in the treatment of multiple myeloma: benefit for a small proportion of patients? Med Oncol. 2000 May;17(2):77-84. doi: 10.1007/BF02796202.
• Background Palumbo A, Boccadoro M, Garino LA, Gallone G, Frieri R, Pileri A. Multiple myeloma: intensified maintenance therapy with recombinant interferon-alpha-2b plus glucocorticoids. Eur J Haematol. 1992 Aug;49(2):93-7. doi: 10.1111/j.1600-0609.1992.tb00037.x.
• Background Salmon SE, Crowley JJ, Balcerzak SP, Roach RW, Taylor SA, Rivkin SE, Samlowski W. Interferon versus interferon plus prednisone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol. 1998 Mar;16(3):890-6. doi: 10.1200/JCO.1998.16.3.890.
• Background Berenson JR, Crowley JJ, Grogan TM, Zangmeister J, Briggs AD, Mills GM, Barlogie B, Salmon SE. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood. 2002 May 1;99(9):3163-8. doi: 10.1182/blood.v99.9.3163.
• Background International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003 Jun;121(5):749-57.
• Background Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998 Sep;102(5):1115-23. doi: 10.1046/j.1365-2141.1998.00930.x. No abstract available.
• Background Rizzo JD, Lichtin AE, Woolf SH, Seidenfeld J, Bennett CL, Cella D, Djulbegovic B, Goode MJ, Jakubowski AA, Lee SJ, Miller CB, Rarick MU, Regan DH, Browman GP, Gordon MS; American Society of Clinical Oncology; Americcan Society of Hematology. Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. Blood. 2002 Oct 1;100(7):2303-20. doi: 10.1182/blood-2002-06-1767.
• Background Rizzo JD, Lichtin AE, Woolf SH, Seidenfeld J, Bennett CL, Cella D, Djulbegovic B, Goode MJ, Jakubowski AA, Lee SJ, Miller CB, Rarick MU, Regan DH, Browman GP, Gordon MS; American Society of Clinical Oncology. American Society of Hematology. Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol. 2002 Oct 1;20(19):4083-107. doi: 10.1200/JCO.2002.07.177.
• Background Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365.
• Background 33. Fayers P, Aaonson N, Bjordal K, Curran D, Groenvold M, on behalf of the EORTC Quality of life study group. EORTC QLQ-C30 Scoring Manual: 2nd Ed. 1999. ISBN 2-930064-16-1.1
• Background Stead ML, Brown JM, Velikova G, Kaasa S, Wisloff F, Child JA, Hippe E, Hjorth M, Sezer O, Selby P. Development of an EORTC questionnaire module to be used in health-related quality-of-life assessment for patients with multiple myeloma. European Organization for Research and Treatment of Cancer Study Group on Quality of Life. Br J Haematol. 1999 Mar;104(3):605-11. doi: 10.1046/j.1365-2141.1999.01206.x.
• Mateos MV, Oriol A, Martinez-Lopez J, Teruel AI, Bengoechea E, Palomera L, de Arriba F, Esseltine DL, Cakana A, Pei L, van de Velde H, Miguel JS. Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials. Ann Hematol. 2016 Dec;95(12):2033-2041. doi: 10.1007/s00277-016-2835-3. Epub 2016 Oct 14.
• Mateos MV, Martinez-Lopez J, Hernandez MT, Ocio EM, Rosinol L, Martinez R, Teruel AI, Gutierrez NC, Martin Ramos ML, Oriol A, Bargay J, Bengoechea E, Gonzalez Y, Perez de Oteyza J, Gironella M, Encinas C, Martin J, Cabrera C, Paiva B, Cedena MT, Puig N, Blade J, Lahuerta JJ, San-Miguel J. Sequential vs alternating administration of VMP and Rd in elderly patients with newly diagnosed MM. Blood. 2016 Jan 28;127(4):420-5. doi: 10.1182/blood-2015-08-666537. Epub 2015 Oct 23.
• Mateos MV, Oriol A, Martinez-Lopez J, Teruel AI, Lopez de la Guia A, Lopez J, Bengoechea E, Perez M, Martinez R, Palomera L, de Arriba F, Gonzalez Y, Hernandez JM, Granell M, Bello JL, Bargay J, Penalver FJ, Martin-Mateos ML, Paiva B, Montalban MA, Blade J, Lahuerta JJ, San-Miguel JF. GEM2005 trial update comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators? Blood. 2014 Sep 18;124(12):1887-93. doi: 10.1182/blood-2014-05-573733.
• Martinez-Lopez J, Fernandez-Redondo E, Garcia-Sanz R, Montalban MA, Martinez-Sanchez P, Pavia B, Mateos MV, Rosinol L, Martin M, Ayala R, Martinez R, Blanchard MJ, Alegre A, Besalduch J, Bargay J, Hernandez MT, Sarasquete ME, Sanchez-Godoy P, Fernandez M, Blade J, San Miguel JF, Lahuerta JJ; GEM (Grupo Espanol Multidisciplinar de Melanoma)/PETHEMA (Programa para el Estudio de la Terapeutica en Hemopatias Malignas) cooperative study group. Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study. Br J Haematol. 2013 Dec;163(5):581-9. doi: 10.1111/bjh.12576. Epub 2013 Oct 3.
• Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, Lopez de la Guia A, Lopez J, Bengoechea E, Perez M, Polo M, Palomera L, de Arriba F, Gonzalez Y, Hernandez JM, Granell M, Bello JL, Bargay J, Penalver FJ, Ribera JM, Martin-Mateos ML, Garcia-Sanz R, Lahuerta JJ, Blade J, San-Miguel JF. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012 Sep 27;120(13):2581-8. doi: 10.1182/blood-2012-05-427815. Epub 2012 Aug 13.
• Lopez-Corral L, Mateos MV, Corchete LA, Sarasquete ME, de la Rubia J, de Arriba F, Lahuerta JJ, Garcia-Sanz R, San Miguel JF, Gutierrez NC. Genomic analysis of high-risk smoldering multiple myeloma. Haematologica. 2012 Sep;97(9):1439-43. doi: 10.3324/haematol.2011.060780. Epub 2012 Feb 13.
• Mateos MV, Gutierrez NC, Martin-Ramos ML, Paiva B, Montalban MA, Oriol A, Martinez-Lopez J, Teruel AI, Bengoechea E, Martin A, Diaz-Mediavilla J, de Arriba F, Palomera L, Hernandez JM, Sureda A, Bargay J, Penalver FJ, Ribera JM, Martin-Mateos ML, Fernandez M, Garcia-Sanz R, Vidriales MB, Blade J, Lahuerta JJ, San Miguel JF. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. 2011 Oct 27;118(17):4547-53. doi: 10.1182/blood-2011-04-345801. Epub 2011 Sep 6.
• Sarasquete ME, Gutierrez NC, Misiewicz-Krzeminska I, Paiva B, Chillon MC, Alcoceba M, Garcia-Sanz R, Hernandez JM, Gonzalez M, San-Miguel JF. Upregulation of Dicer is more frequent in monoclonal gammopathies of undetermined significance than in multiple myeloma patients and is associated with longer survival in symptomatic myeloma patients. Haematologica. 2011 Mar;96(3):468-71. doi: 10.3324/haematol.2010.033845. Epub 2010 Dec 15.
• Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, de Paz R, Garcia-Larana J, Bengoechea E, Martin A, Mediavilla JD, Palomera L, de Arriba F, Gonzalez Y, Hernandez JM, Sureda A, Bello JL, Bargay J, Penalver FJ, Ribera JM, Martin-Mateos ML, Garcia-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalban MA, Lahuerta JJ, Blade J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. doi: 10.1016/S1470-2045(10)70187-X. Epub 2010 Aug 23.

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