Bortezomib (Velcade®), Lenalidomide (Revlimid®) and IV Busulfan (Busilvex®) in Patients Under 65 Years Old

Summary

This protocol is a national, multicenter, comparative, open-label, randomized trial comparing the progression free survival (PFS) of two pre-transplant conditioning regimens (BUMEL versus. MEL-200). A total of 460 patients will be enrolled in the study. Scheduled evaluations and study visits will take place during the pre-treatment, treatment and follow-up periods. The pre-treatment period includes the screening visit in which participants provide informed consent in writing in order to take part in the study. The patient is then assessed to determine his/her eligibility. The selection process will begin 21 days before the first dose of medication is administered (days -21 to 0). During the treatment period, eligible patients will be included in the study and given six cycles of induction treatment with bortezomib/ lenalidomide / dexamethasone (VRD-GEM). Each cycle will last 28 days, during which SC bortezomib will be administered on days 1, 4, 8 and 11, oral lenalidomide on days 1-21 of each cycle, and oral dexamethasone on days 1-4 and 9-12 of the cycle. After the first three induction cycles, and in the absence of progression or unacceptable toxicity, peripheral blood hematopoietic stem cells will be mobilized and collected using G-CSF for later autologous transplantation. Patients will be randomized in a 1:1 allocation ratio to receive conditioning treatment with MEL-200 versus BUMEL. Randomization will take place at the beginning of the study, once the screening is complete and the patient's eligibility verified. Three months after transplantation, patients will receive two cycles of consolidation treatment with VRD-GEM at the same doses administered during induction treatment. Once the treatment phase is complete, patients will begin the follow-up phase in which they will be visited every three months to evaluate disease progression and survival

Timeline

Start

2013-09

Primary completion

2016-11-16

Completion

2016-11-16

Publications

• Lahuerta JJ, San-Miguel J, Jimenez-Ubieto A, Alonso R, Paiva B, Puig N, Cedena MT, Gutierrez NC, Calasanz MJ, Fernandez Guijarro M, Tamayo RR, Rocafiguera AO, Blanchard MJ, Carrillo Cruz E, Martinez-Martinez R, Bargay J, Sureda Balari A, Rubia J, Hernandez Garcia MT, Cabanas V, Montero FC, Bernal LP, Montes YG, Martinez-Lopez J, Rodriguez-Otero P, Krisnik I, Arguinano JM, Gonzalez Garcia ME, Ocio EM, Cruz J, Mateos MV, Rosinol L, Blade J. High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial. Blood. 2025 Oct 9;146(15):1747-1758. doi: 10.1182/blood.2025028313.
• Puig N, Agullo C, Contreras T, Cedena MT, Martinez-Lopez J, Oriol A, Blanchard MJ, Rios R, Inigo MB, Sureda A, Lakhwani S, de la Rubia J, Gonzalez-Calle V, Cabanas V, Palomera L, Moraleda JM, Bargay J, Castro S, Rosinol L, Blade J, San-Miguel JF, Lahuerta JJ, Paiva B, Mateos MV. Measurable residual disease by mass spectrometry and next-generation flow to assess treatment response in myeloma. Blood. 2024 Dec 5;144(23):2432-2438. doi: 10.1182/blood.2024024995.
• Guerrero C, Puig N, Cedena MT, Calasanz MJ, Gutierrez NC, Fernandez M, Oriol A, Rios-Tamayo R, Hernandez MT, Martinez-Martinez R, Bargay J, de Arriba F, Palomera L, Gonzalez-Rodriguez AP, Gonzalez Perez MS, Orfao A, Mateos MV, Martinez-Lopez J, Rosinol L, Blade J, Lahuerta JJ, San-Miguel JF, Paiva B. Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma. Blood. 2024 Feb 15;143(7):597-603. doi: 10.1182/blood.2023022083.
• Lakhwani S, Rosinol L, Puig N, Pico-Picos MA, Medina-Gonzalez L, Martinez-Lopez J, Paiva B, Cedena MT, Oriol A, Rios-Tamayo R, Blanchard MJ, Jarque I, Bargay J, Moraleda JM, Carrillo-Cruz E, Sureda A, Krsnik I, Gonzalez E, Casado LF, Marti JM, Encinas C, De Arriba F, Palomera L, Sampol A, Gonzalez-Montes Y, Motllo C, De La Cruz J, Alonso R, Mateos MV, Blade J, Lahuerta JJ, San-Miguel J, Hernandez MT. Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection. Haematologica. 2024 Jun 1;109(6):1909-1917. doi: 10.3324/haematol.2023.284154.
• 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.
• Cardona-Benavides IJ, Misiewicz-Krzeminska I, Rojas EA, De Ramon C, Sanz-Solas A, Isidro I, Quwaider D, Lopez-Guerrero AM, Cuadrado M, Calasanz MJ, Rosinol L, Martinez-Lopez J, San Miguel JF, Mateos MV, Corchete LA, Gutierrez NC. Quantification of cyclin D1 and D2 proteins in multiple myeloma identifies different expression patterns from those revealed by gene expression profiling. Haematologica. 2024 Mar 1;109(3):877-887. doi: 10.3324/haematol.2023.283445.
• Puig N, Contreras MT, Agullo C, Martinez-Lopez J, Oriol A, Blanchard MJ, Rios R, Martin J, Inigo MB, Sureda A, Hernandez MT, de la Rubia J, Gonzalez-Calle V, Krsnik I, Cabanas V, Palomera L, Moraleda JM, Bargay J, Cedena MT, Paiva B, Rosinol L, Blade J, San Miguel J, Lahuerta JJ, Mateos MV. Mass spectrometry vs immunofixation for treatment monitoring in multiple myeloma. Blood Adv. 2022 Jun 14;6(11):3234-3239. doi: 10.1182/bloodadvances.2021006762.
• Botta C, Maia C, Garces JJ, Termini R, Perez C, Manrique I, Burgos L, Zabaleta A, Alignani D, Sarvide S, Merino J, Puig N, Cedena MT, Rossi M, Tassone P, Gentile M, Correale P, Borrello I, Terpos E, Jelinek T, Paiva A, Roccaro A, Goldschmidt H, Avet-Loiseau H, Rosinol L, Mateos MV, Martinez-Lopez J, Lahuerta JJ, Blade J, San-Miguel JF, Paiva B. FlowCT for the analysis of large immunophenotypic data sets and biomarker discovery in cancer immunology. Blood Adv. 2022 Jan 25;6(2):690-703. doi: 10.1182/bloodadvances.2021005198.
• Goicoechea I, Puig N, Cedena MT, Burgos L, Cordon L, Vidriales MB, Flores-Montero J, Gutierrez NC, Calasanz MJ, Ramos MM, Lara-Astiaso D, Vilas-Zornoza A, Alignani D, Rodriguez I, Sarvide S, Alameda D, Garces JJ, Rodriguez S, Fresquet V, Celay J, Garcia-Sanz R, Martinez-Lopez J, Oriol A, Rios R, Martin-Sanchez J, Martinez-Martinez R, Sarra J, Hernandez MT, de la Rubia J, Krsnik I, Moraleda JM, Palomera L, Bargay J, Martinez-Climent JA, Orfao A, Rosinol L, Mateos MV, Lahuerta JJ, Blade J, San Miguel J, Paiva B. Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma. Blood. 2021 Jan 7;137(1):49-60. doi: 10.1182/blood.2020006731.
• Rosinol L, Oriol A, Rios R, Sureda A, Blanchard MJ, Hernandez MT, Martinez-Martinez R, Moraleda JM, Jarque I, Bargay J, Gironella M, de Arriba F, Palomera L, Gonzalez-Montes Y, Marti JM, Krsnik I, Arguinano JM, Gonzalez ME, Gonzalez AP, Casado LF, Lopez-Anglada L, Paiva B, Mateos MV, San Miguel JF, Lahuerta JJ, Blade J. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood. 2019 Oct 17;134(16):1337-1345. doi: 10.1182/blood.2019000241.

Drugs

Indications