GEM05 for Patients With Multiple Myeloma Under 65 Years

Summary

The primary objective is to compare safety and efficacy of three induction treatments: VBMCP-VBAD / Velcade versus Thalidomide / Dexamethasone versus Velcade / Thalidomide / Dexamethasone. The second one is to evaluate the ability of stem cell mobilization after the treatments in order to do an autologous transplant. Otherwise this study wants to compare the safety and efficacy of the maintenance treatments: Interferón a-2b versus Thalidomide versus Thalidomide/Velcade.

Timeline

Start

2006-03

Primary completion

2008-12

Completion

2008-12

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 Oken MM. Management of Myeloma: Current and Future Approaches. Cancer Control. 1998 May;5(3):218-225. doi: 10.1177/107327489800500302.
• 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 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 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 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 Gore ME, Selby PJ, Viner C, Clark PI, Meldrum M, Millar B, Bell J, Maitland JA, Milan S, Judson IR, et al. Intensive treatment of multiple myeloma and criteria for complete remission. Lancet. 1989 Oct 14;2(8668):879-82. doi: 10.1016/s0140-6736(89)91548-1.
• 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 Hjorth M, Holmberg E, Rodjer S, Turesson I, Westin J, Wisloff F. Survival in conventionally treated younger (<60 years) multiple myeloma patients: no improvement during two decades. Nordic Myeloma Study Group (NMSG). Eur J Haematol. 1999 Apr;62(4):271-7. doi: 10.1111/j.1600-0609.1999.tb01757.x.
• Background Lokhorst HM, Schattenberg A, Cornelissen JJ, Thomas LL, Verdonck LF. Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood. 1997 Nov 15;90(10):4206-11.
• Background Gahrton G, Tura S, Ljungman P, Blade J, Brandt L, Cavo M, Facon T, Gratwohl A, Hagenbeek A, Jacobs P, et al. Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol. 1995 Jun;13(6):1312-22. doi: 10.1200/JCO.1995.13.6.1312.
• Background Bensinger WI, Buckner CD, Anasetti C, Clift R, Storb R, Barnett T, Chauncey T, Shulman H, Appelbaum FR. Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome. Blood. 1996 Oct 1;88(7):2787-93.
• Background Powles R, Raje N, Milan S, Millar B, Shepherd V, Mehta J, Singhal S, Kulkarni S, Viner C, Gore M, Cunningham D, Treleaven J. Outcome assessment of a population-based group of 195 unselected myeloma patients under 70 years of age offered intensive treatment. Bone Marrow Transplant. 1997 Sep;20(6):435-43. doi: 10.1038/sj.bmt.1700917.
• Background Vesole DH, Tricot G, Jagannath S, Desikan KR, Siegel D, Bracy D, Miller L, Cheson B, Crowley J, Barlogie B. Autotransplants in multiple myeloma: what have we learned? Blood. 1996 Aug 1;88(3):838-47.
• Background Barlogie B, Jagannath S, Naucke S, Mattox S, Bracy D, Crowley J, Tricot G, Alexanian R. Long-term follow-up after high-dose therapy for high-risk multiple myeloma. Bone Marrow Transplant. 1998 Jun;21(11):1101-7. doi: 10.1038/sj.bmt.1701182.
• Background 23. Barlogie B, Ayers D, Spoon D, et al. Towards curing myeloma. durable CR in the absence of chromosome 13 deletion and with timely application of two cycles of melphalan-based high dose therapy. Proceedings of the VII International Multiple Myeloma Workshop, Stockholm, September 1999, pp: 49.
• Background Alexanian R, Weber D, Delasalle K, Dimopoulos M, Giralt S, Champlin R. Early myeloablative therapy with autologous stem cells for multiple myeloma in remission with primary therapy. Proceedings of the VII International Multiple Myeloma Workshop, Stockholm, September 1999, pp: 61.
• Background 25. Bladé J, Esteve J, Rives S, et al. Early autologous stem cell transplantation versus standard chemotherapy after first response in multipple myeloma: a report of a non-randomized study from a single institution. Proceedings of the VII International Multiple Myeloma Workshop, Stockholm, September 1999, pp: 148.
• Background Lahuerta JJ, Martinez-Lopez J, Serna JD, Blade J, Grande C, Alegre A, Vazquez L, Garcia-Larana J, Sureda A, Rubia JD, Conde E, Martinez R, Perez-Equiza K, Moraleda JM, Leon A, Besalduch J, Cabrera R, Miguel JD, Morales A, Garcia-Ruiz JC, Diaz-Mediavilla J, San-Miguel J. Remission status defined by immunofixation vs. electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients. Br J Haematol. 2000 May;109(2):438-46. doi: 10.1046/j.1365-2141.2000.02012.x.
• 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 Palumbo A, Triolo S, Argentino C, Bringhen S, Dominietto A, Rus C, Omede P, Tarella C, Pileri A, Boccadoro M. Dose-intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood. 1999 Aug 15;94(4):1248-53.
• Background Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S, Bracy D, Salmon S, Jacobson J, Crowley J, Tricot G. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1997 Feb 1;89(3):789-93.
• Background Lenhoff S, Hjorth M, Holmberg E, Turesson I, Westin J, Nielsen JL, Wisloff F, Brinch L, Carlson K, Carlsson M, Dahl IM, Gimsing P, Hippe E, Johnsen HE, Lamvik J, Lofvenberg E, Nesthus I, Rodjer S. Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Nordic Myeloma Study Group. Blood. 2000 Jan 1;95(1):7-11.
• Background Blade J, San Miguel JF, Fontanillas M, Alcala A, Maldonado J, Garcia-Conde J, Conde E, Conzalez-Brito G, Moro MJ, Escudero ML, Trujillo J, Pascual A, Rozman C, Estape J, Montserrat E. Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated. J Clin Oncol. 1996 Jul;14(7):2167-73. doi: 10.1200/JCO.1996.14.7.2167.
• Background Alexanian R, Dimopoulos MA, Hester J, Delasalle K, Champlin R. Early myeloablative therapy for multiple myeloma. Blood. 1994 Dec 15;84(12):4278-82.
• Background Vesole DH, Barlogie B, Jagannath S, Cheson B, Tricot G, Alexanian R, Crowley J. High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants. Blood. 1994 Aug 1;84(3):950-6.
• Background Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. doi: 10.1056/NEJM199911183412102.
• Background 35. Singhal S, Mehta J., Eddlemon P., Gray P., Cromer J., Desikan R., Ayers D., Siegel D., Munshi N., Anaissie E., Kantarjian H., Zeldis J., Barlogie B. Marked anti-tumor effect from anti-angiogenesis therapy with thalidomide in high risk refractory multiple myeloma. Blood, 1998; 92(suppl 1):318a (abstract).
• 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 38. Rajkumar S, Blood E, Vesole D, Shepard R, Greipp P. Thalidomide plus dexamethasone versus dexamethasone alone in newly diagnosed multiple myeloma. Blood 2004. Volume 104, issue 11. Abstract 205
• 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 41. 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 42. 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 43. 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 44. 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 Desikan KR, Barlogie B, Jagannath S, Vesole DH, Siegel D, Fassas A, Munshi N, Singhal S, Mehta J, Tindle S, Nelson J, Bracy D, Mattox S, Tricot G. Comparable engraftment kinetics following peripheral-blood stem-cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma. J Clin Oncol. 1998 Apr;16(4):1547-53. doi: 10.1200/JCO.1998.16.4.1547.
• Background 46. 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.
• Rosinol L, Hebraud B, Oriol A, Colin AL, Rios Tamayo R, Hulin C, Blanchard MJ, Caillot D, Sureda A, Hernandez MT, Arnulf B, Mateos MV, Macro M, San-Miguel J, Belhadj K, Lahuerta JJ, Garelik MB, Blade J, Moreau P. Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma. Front Oncol. 2023 Nov 2;13:1197340. doi: 10.3389/fonc.2023.1197340. eCollection 2023.
• Sonneveld P, Goldschmidt H, Rosinol L, Blade J, Lahuerta JJ, Cavo M, Tacchetti P, Zamagni E, Attal M, Lokhorst HM, Desai A, Cakana A, Liu K, van de Velde H, Esseltine DL, Moreau P. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol. 2013 Sep 10;31(26):3279-87. doi: 10.1200/JCO.2012.48.4626. Epub 2013 Jul 29.
• Rosinol L, Oriol A, Teruel AI, Hernandez D, Lopez-Jimenez J, de la Rubia J, Granell M, Besalduch J, Palomera L, Gonzalez Y, Etxebeste MA, Diaz-Mediavilla J, Hernandez MT, de Arriba F, Gutierrez NC, Martin-Ramos ML, Cibeira MT, Mateos MV, Martinez J, Alegre A, Lahuerta JJ, San Miguel J, Blade J; Programa para el Estudio y la Terapeutica de las Hemopatias Malignas/Grupo Espanol de Mieloma (PETHEMA/GEM) group. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 23;120(8):1589-96. doi: 10.1182/blood-2012-02-408922. Epub 2012 Jul 12.
• 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.

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