GEM05 for Patients With Multiple Myeloma Under 65 Years

NCT00461747 | Completed Phase 3 DMC

• 1 other identifier: 2005-001110-41
• Study Type: interventional
• Target: 390
• Locations: 1 country
• Sites: 79

Brief 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.

Conditions

Multiple Myeloma

Keywords

Untreated; Transplant; Younger

Outcome Measures

Primary Outcomes (1)

• The primary objective is to compare safety and efficacy of three induction treatments: VBMCP-VBAD / Velcade versus Thalidomide / Dexamethasone versus Velcade / Thalidomide / Dexamethasone.

  2 years

Secondary Outcomes (1)

• 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

  2 years

Study Arms (3)

A

ACTIVE COMPARATOR

Four alternating cycles of VBMCP/VBAD + Velcade VBMCP: Vincristine, 0,03 mg/Kg (iv) day 1, BCNU, 0,5 mg/Kg iv day 1, Cyclophosphamide, 10 mg/Kg iv day 1, Melfalán, 0,25 mg/Kg oral days 1 to 4 Prednisone, 1 mg/Kg oral days 1 to 4; 0,5 mg/Kg oral days 5 to 8 and 0,25 mg/Kg oral days 9 to 12. VBAD : Vincristine, 1mg via iv day 1, BCNU, 30 mg/m2 iv day 1, Adriamycine, 40mg/m2 iv day 1 Dexamethasone, 40 mg oral days 1 to 4, 9 to 12 and 17 to 20. The interval between VBMCP and VBAD is 5 weeks and between VBAD and VBMCP is 4 weeks. The patients will received two cycles of VBMCP and two cycles of VBAD. After 4 weeks of last cycle of VBAD, patients will received two cycles of Velcade, 1,3 mg/ m2 iv twice a week (days 1, 4, 8 and 11), followed by 10 days without treatment

Drug: VBMCP/VBAD/Velcade

B

EXPERIMENTAL

Six cycles of 4 weeks of Thalidomide/Dexamethasone. Thalidomide day 1, cycle 1 (50 mg/day v.o). If toxicity \< grade 2, dose will be 100 mg/day on day 15, cycle 1 and 200 mg/day on day 1, cycle 2. Dexamethasone:40 mg/day v.o.days 1 to 4 and 9 to 12, with a period without treatment of 16 days

Drug: Thalidomide/Dexamethasone

C

EXPERIMENTAL

Thalidomide: day 1 cycle 1 (50 mg/day).If toxicity is \< grade 2, the dose will be increased (100 mg/day) at day 15 cycle 1 and (200 mg de Thalidomide) at day 1 cycle 2. Dexamethasone: 40 mg/day v.o days 1 to 4 and 8 to 11, with a period without treatment of 17 days. Velcade: 1,3 mg/m2 iv twice a week (days 1, 4, 8 and 11) with a period without treatment of 17 days.

Drug: Velcade/Thalidomide/Dexamethasone

Interventions

VBMCP/VBAD/Velcade DRUG

VBMCP: Vincristine, 0,03 mg/Kg (iv) day 1, BCNU, 0,5 mg/Kg iv day 1, Cyclophosphamide, 10 mg/Kg iv day 1, Melfalan, 0,25 mg/Kg oral days 1 to 4 Prednisone, 1 mg/Kg oral days 1 to 4; 0,5 mg/Kg oral days 5 to 8 and 0,25 mg/Kg oral days 9 to 12. VBAD : Vincristine, 1mg via iv day 1, BCNU, 30 mg/m2 iv day 1, Adriamycine, 40mg/m2 iv day 1 Dexamethasone, 40 mg oral days 1 to 4, 9 to 12 and 17 to 20.

A

Thalidomide/Dexamethasone DRUG

Thalidomide day 1, cycle 1 (50 mg/day v.o). If toxicity \< grade 2, dose will be 100 mg/day on day 15, cycle 1 and 200 mg/day on day 1, cycle 2. Dexamethasone:40 mg/day v.o.days 1 to 4 and 9 to 12, with a period without treatment of 16 days

B

Velcade/Thalidomide/Dexamethasone DRUG

Thalidomide: day 1 cycle 1 (50 mg/day).If toxicity is \< grade 2, the dose increased (100 mg/day) at day 15 cycle 1 and (200 mg de Thalidomide) at day 1 cycle 2. Dexamethasone: 40 mg/day v.o days 1 to 4 and 8 to 11, with a period without treatment of 17 days. Velcade: 1,3 mg/m2 iv twice a week (days 1, 4, 8 and 11) with a period without treatment of 17 days

C

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be able to comply with the protocol requirements
• Must voluntary sign the informed consent before performance of any study-related procedure not part of normal medical care,
• Age \<65 years and possibly to do an autologous transplant.
• Patient recently diagnosed with symptomatic Multiple Myeloma who has not received any previous chemotherapy treatment for Multiple Myeloma.
• Patient has a measurable disease defined as quantifiable serum monoclonal protein value and, where applicable, urine Light-chain excretion of ≥ 200 mg/24 hours.
• ECOG \< 2.
• El patient has a life-expectancy \> 3 months.
• Patient has the following laboratory values before beginning induction treatment:
• Platelet count ≥ 50000/mm3, hemoglobin ≥ 8 g/dl and absolute neutrophil count ≥ 1000/mm3. Lower values are allowed if they are due to marrow infiltration.
• Corrected serum calcium \<14mg/dl.
• Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.
• Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal.
• Total bilirubin: ≤1.5 x the upper limit of normal.
• Serum creatinine ≤ 2 mg/dl.
• For Patients included in Thalidomide branches: women of childbearing age must not have sex unless they use two anticonceptive methods beginning 4 weeks before the first dose, during all the study until 4 weeks after the last one.

You may not qualify if:

• Non-secretor Myeloma.
• Patients previously received treatment to Multiple Myeloma, except steroids doses for urgency or bisphosphonates or radiotherapy before beginning treatment.
• Patients with \< Grade 2 peripheral neuropathy within 14 days before enrolment.
• Patient had major surgery within 4 weeks before enrolment.
• Patient has hypersensitivity to bortezomib, boron or mannitol or Thalidomide.
• Patient has received other investigational drugs within 30 days before enrolment.
• Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection.
• Patient had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
• Pregnancy or breast-feed women.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (79)

Hospital General de Alicante

Alicante, Alicante, Spain

Location

Hospital Royo Villanova

Zaragoza, Aragon, Spain

Location

Hospital Ntra. Sra. Sonsoles

Ávila, Avila, Spain

Location

Xarxa assistencial de Manresa

Manresa, Barcelona, Spain

Location

Corporació Sanitària Parc Taulí

Sabadell, Barcelona, Spain

Location

Hospital general de Castellón

Castelló, Castellón, Spain

Location

Hospital Clínico San Carlos de Madrid

Madrid, Madrid, Spain

Location

Hospital Universitario de la Princesa

Madrid, Madrid, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Navarre, Spain

Location

Hospital Central de Asturias

Oviedo, Oviedo, Spain

Location

Hospital del Río Carrión

Palencia, Palencia, Spain

Location

Hospital Joan XXIII

Tarragona, Tarragona, Spain

Location

Hospital Clínic

Valencia, Valencia, Spain

Location

Hospital La Fe

Valencia, Valencia, Spain

Location

Hospital Clínico Lozano Blesa

Zaragoza, Zaragoza, Spain

Location

Complejo Hospitalario Universitario de Albacete

Albacete, Spain

Location

Fundación Hospital Alcorcón

Alcorcón, Spain

Location

Hospital Regional Universitario Infanta Cristina

Badajoz, Spain

Location

Hospital de Badalona Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Vall D'Hebron

Barcelona, Spain

Location

Basurtuko Ospitalea

Bilbao, Spain

Location

Hospital de Cruces

Bilbao, Spain

Location

Hospital Virgen del Puerto

Cáceres, Spain

Location

Hospital Nuestra Señora de Alarcos

Ciudad Real, Spain

Location

Hospital Virgen de la Luz

Cuenca, Spain

Location

Hospital Donostia

Donostia / San Sebastian, Spain

Location

Hospital General de Elda

Elda, Spain

Location

Hospital Universitario de Getafe

Getafe, Spain

Location

Hospital General de Guadalajara

Guadalajara, Spain

Location

Hospital de San Jorge

Huesca, Spain

Location

Hospital General de Lanzarote

Lanzarote, Spain

Location

Complejo Hospitalario León

León, Spain

Location

Complexo Hospitalario Xeral-Calde

Lugo, Spain

Location

Clínica Moncloa

Madrid, Spain

Location

Clínica Puerta de Hierro

Madrid, Spain

Location

Clínica Rúber

Madrid, Spain

Location

Fundación Jiménez Díaz

Madrid, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Central de la Defensa

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Fundación Hospital Sant Joan de Déu de Martorell

Martorell, Spain

Location

Hospital de Mérida

Mérida, Spain

Location

Hospital General Morales Meseguer

Murcia, Spain

Location

Hospital Santa María del Rosell

Murcia, Spain

Location

Hospital Virgen del Castillo de Yecla

Murcia, Spain

Location

Hospital de Gran Canaria Doctor Negrín

Palma de Gran Canaria, Spain

Location

Complejo Asistencial Son Dureta

Palma de Mallorca, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Spain

Location

Hospital Verge del Toro

Palma de Mallorca, Spain

Location

Hospital de Navarra

Pamplona, Spain

Location

Hospital Virgen del Camino

Pamplona, Spain

Location

Complejo Hospitalario de Pontevedra_Hospital Montecelo

Pontevedra, Spain

Location

Complejo Hospitalario de Pontevedra_Hospital Provincial

Pontevedra, Spain

Location

Hospital de Sagunto

Sagunto, Spain

Location

Hospital Clínico de Salamanca

Salamanca, Spain

Location

Hospital San Pedro de Alcántara

San Pedro, Spain

Location

Clínica Sant Camil

Sant Pere de Ribes, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain

Location

Hospital General de Segovia

Segovia, Spain

Location

Hospital Nuestra Señora del Prado

Toledo, Spain

Location

Hospital Virgen de la Salud

Toledo, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, Spain

Location

Hospital Arnau de Vilanova

Valencia, Spain

Location

Hospital Dr. Peset

Valencia, Spain

Location

Hospital Francesc de Borja

Valencia, Spain

Location

Hospital General Básico de la Defensa

Valencia, Spain

Location

Hospital Clínico de Valladolid

Valladolid, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Spain

Location

Comarcal de Vinaros

Vinaròs, Spain

Location

Hospital Txagorritxu

Vitoria-Gasteiz, Spain

Location

Hospital de Galdakao

Vizcaya, Spain

Location

Hospital Virgen de la Concha

Zamora, Spain

Location

Hospital Miguel Servet

Zaragoza, Spain

Location

Related Publications (57)

• 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.

  PMID: 10735013 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.

  PMID: 10564693 BACKGROUND

• Oken MM. Management of Myeloma: Current and Future Approaches. Cancer Control. 1998 May;5(3):218-225. doi: 10.1177/107327489800500302.

  PMID: 10761055 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.

  PMID: 5933438 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.

  PMID: 5818682 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.

  PMID: 6366141 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.

  PMID: 1999714 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.

  PMID: 1346171 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.

  PMID: 8501503 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.

  PMID: 9118039 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.

  PMID: 9850028 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.

  PMID: 2571812 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.

  PMID: 2571813 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.

  PMID: 10227461 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.

  PMID: 9354693 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.

  PMID: 7751876 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.

  PMID: 8839877 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.

  PMID: 9313875 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.

  PMID: 8704239 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.

  PMID: 9645572 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.

  PMID: 10848839 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.

  PMID: 8649495 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.

  PMID: 10438712 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.

  PMID: 9028309 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.

  PMID: 10607678 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.

  PMID: 8683251 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.

  PMID: 7994043 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.

  PMID: 7913845 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.

  PMID: 10564685 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.

  PMID: 12409330 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.

  PMID: 12506164 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.

  PMID: 12826635 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.

  PMID: 15461622 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.

  PMID: 9552064 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.

  PMID: 10871813 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.

  PMID: 1397246 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.

  PMID: 9508170 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.

  PMID: 11964279 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.

  PMID: 12780789 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.

  PMID: 9753033 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.

  PMID: 12239138 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.

  PMID: 12351606 BACKGROUND

• 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.

  PMID: 38023148 DERIVED

• 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.

  PMID: 23897961 DERIVED

• 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.

  PMID: 22791289 DERIVED

• 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.

  PMID: 21160068 DERIVED

Related Links

• Spanish association of Haematology

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Thalidomide; Dexamethasone; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Study Officials

• Bladé Joan, Dr

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 17, 2007
• First Posted: April 18, 2007
• Study Start: March 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: September 18, 2009

Record last verified: 2009-09

Locations

ES (79)