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

NCT ID: NCT01916252

Last Updated: 2017-09-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

460 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2016-11-16

Brief Summary

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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

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MEL-200

bortezomib/lenalidomide/dexamethasone (VRD-GEM) induction treatment followed by high-dose melphalan-200 (MEL-200)

Group Type ACTIVE_COMPARATOR

bortezomib (Velcade ®)

Intervention Type DRUG

lenalidomide (Revlimid®)

Intervention Type DRUG

Dexamethasone acetate

Intervention Type DRUG

Melphalan

Intervention Type DRUG

BUMEL

bortezomib/lenalidomide/dexamethasone (VRD-GEM) induction treatment followed by busulfan-melphalan (BUMEL) chemotherapy and consolidation with VRD-GEM

Group Type ACTIVE_COMPARATOR

bortezomib (Velcade ®)

Intervention Type DRUG

lenalidomide (Revlimid®)

Intervention Type DRUG

busulfan (Busilvex ®)

Intervention Type DRUG

Dexamethasone acetate

Intervention Type DRUG

Melphalan

Intervention Type DRUG

Interventions

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bortezomib (Velcade ®)

Intervention Type DRUG

lenalidomide (Revlimid®)

Intervention Type DRUG

busulfan (Busilvex ®)

Intervention Type DRUG

Dexamethasone acetate

Intervention Type DRUG

Melphalan

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* The patient must, in the opinion of the investigator, be capable of complying with all requirements of the trial
* Have signed the informed consent form
* Be between 18 and 65 years of age and a candidate for autologous stem cell transplant
* Have an ECOG Performance Status \> 2 (or 3 if the ECOG is due to myeloma)
* Newly diagnosed patient with symptomatic multiple myeloma based on standard criteria, who has not received any prior chemotherapy treatment for Multiple Myeloma.
* Patient must have measurable disease, defined by the following criteria:

For secretory MM, measurable disease is defined by any quantifiable value of serum M-protein (IgG ≥ 10 g/L or IgA \> 5 g/L) and/or, when applicable, an excretion of light chain in urine ≥ 200 mg/24 hours.

For oglio- or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas, which is determined by clinical exam or radiographic techniques.

* Life expectancy \> 3 months.
* The patient must have the following laboratory values in the 21 days prior to initiation of treatment (day 1, cycle 1):

Platelet count ≥ 100 x 109/L and absolute neutrophil count of ≥ 1.0 x 109/L Corrected serum calcium \< 14 mg/dL. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x the upper limit of normal (ULN).

Total bilirubin within normal limits. Serum creatinine ≤ 2 mg/dL

\- Women of childbearing potential and men (including vasectomized men whose partners are women of childbearing potential), must use two methods of contraception during the entire course of treatment, during dose interruptions and for up to three months after receiving the final dose

Exclusion Criteria

* Non-secretory myeloma without measurable plasmacytomas.
* Patients who have undergone prior treatment for multiple myeloma, with the exception of emergency treatment using steroid pulses, bisphosphonates, or radiotherapy received before beginning induction treatment.
* Peripheral neuropathy ≥ grade 2 in the 21 days prior to inclusion.
* Known hypersensitivity to bortezomib, boric acid, mannitol or lenalidomide.
* Patients that have received any investigational agent in the 28 days prior to inclusion in the study.
* Patients who have had a myocardial infarction in the six months prior to inclusion in this study or who are a class III or IV according to the New York Heart Association (NYHA) functional classification system, heart failure, unstable angina, uncontrolled ventricular arrhythmias or acute ischemia detected by electrocardiogram, or nervous system disorders.
* Patients currently enrolled in another clinical trial or receiving any type of investigational agent.
* Patients who are seropositive for HBV, HCV or HIV.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen, LP

INDUSTRY

Sponsor Role collaborator

Celgene

INDUSTRY

Sponsor Role collaborator

Pierre Fabre Medicament

INDUSTRY

Sponsor Role collaborator

PETHEMA Foundation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital Son Espases (Son Dureta)

Mallorca, Balearic Islands, Spain

Site Status

Hospital Son Llátzer

Palma de Mallorca, Balearic Islands, Spain

Site Status

Hospital Durán i Reynals - ICO L´Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status

H. Althaia, Xarxa Asistencial de Manresa

Manresa, Barcelona, Spain

Site Status

Hospital de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Canary Islands, Spain

Site Status

Hospital Esp. de Jerez de la Frontera

Jerez de la Frontera, Cádiz, Spain

Site Status

Hospital Nuestra Señora del Prado

Talavera de La Reina, Madrid, Spain

Site Status

Complejo Universitario de Toledo

Toledo, Madrid, Spain

Site Status

Hospital General de Albacete

Albacete, , Spain

Site Status

Hospital Univ. Fundación de Alcorcón

Alcorcón, , Spain

Site Status

Hospital General Univ. de Alicante

Alicante, , Spain

Site Status

Hospital Torrevieja Salud UTE

Alicante, , Spain

Site Status

Hospital del Tajo

Aranjuez, , Spain

Site Status

Hospital German Trias i Pujol

Badalona, , Spain

Site Status

Hospital de Cruces

Barakaldo, , Spain

Site Status

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Vall d´Hebrón

Barcelona, , Spain

Site Status

Hospital Universitario de Burgos

Burgos, , Spain

Site Status

Hospital General Univ. Santa Lucía

Cartagena, , Spain

Site Status

Hospital General de Castellón

Castellon, , Spain

Site Status

Hospital San Pedro de Alcántara (Complejo Hospitalario de Cáceres)

Cáceres, , Spain

Site Status

Hospital General de Ciudad Real

Ciudad Real, , Spain

Site Status

Hospital del Vinalopó

Elche, , Spain

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Hospital de Fuenlabrada

Fuenlabrada, , Spain

Site Status

Hospital de Cabueñes

Gijón, , Spain

Site Status

H. Univ. de Girona Dr. Josep Trueta (ICO)

Girona, , Spain

Site Status

Complejo Hosp. Virgen de las Nieves

Granada, , Spain

Site Status

Hospital Universitario de Guadalajara

Guadalajara, , Spain

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Hospital Severo Ochoa

Leganés, , Spain

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Hospital de León

León, , Spain

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Hospital Universitari Arnau de Vilanova de Lleida

Lleida, , Spain

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Hospital San Pedro

Logroño, , Spain

Site Status

Centro Oncológico MD Anderson

Madrid, , Spain

Site Status

Fundación Jiménez Díaz-UTE

Madrid, , Spain

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Hospital Clínico Universitario San Carlos

Madrid, , Spain

Site Status

Hospital General Univ. Gregorio Marañón

Madrid, , Spain

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Hospital Infanta Cristina

Madrid, , Spain

Site Status

Hospital Infanta Leonor

Madrid, , Spain

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Hospital Infanta Sofía

Madrid, , Spain

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Hospital Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

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Hospital Universitario de la Princesa

Madrid, , Spain

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Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Madrid Sanchinarro

Madrid, , Spain

Site Status

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, , Spain

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Complejo Hospitalario Costa del Sol

Marbella, , Spain

Site Status

Hospital Morales Meseguer

Murcia, , Spain

Site Status

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Site Status

Complejo Hospitalario Ourense

Ourense, , Spain

Site Status

Hospital Universitario Central Asturias

Oviedo, , Spain

Site Status

Clínica Universidad de Navarra

Pamplona, , Spain

Site Status

Complejo Hospitalario de Navarra (Hospital Virgen del Camino)

Pamplona, , Spain

Site Status

Complejo Hospitalario Pontevedra

Pontevedra, , Spain

Site Status

Hospital de Sabadell (Parc Taulí)

Sabadell, , Spain

Site Status

Hospital Clínico de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario de Donostia

San Sebastián, , Spain

Site Status

Hospital Univ. Marqués de

Santander, , Spain

Site Status

Complejo Universitario de Santiago

Santiago de Compostela, , Spain

Site Status

Hospital General de Segovia

Segovia, , Spain

Site Status

Complejo Hosp. Regional Virgen del Rocío

Seville, , Spain

Site Status

Hospital Nuestra Señora de Valme

Seville, , Spain

Site Status

Hospital Santa Bárbara

Soria, , Spain

Site Status

H. Universitari de Tarragona Joan XXIII

Tarragona, , Spain

Site Status

Hospital Universitari Mutua de Terrassa

Terrassa, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Universitario Dr. Peset

Valencia, , Spain

Site Status

Hospital Universitario La Fe

Valencia, , Spain

Site Status

Hospital Clínico de Valladolid

Valladolid, , Spain

Site Status

Hospital Universitario Río Hortega

Valladolid, , Spain

Site Status

Hospital de Txagorritxu

Vitoria-Gasteiz, , Spain

Site Status

Hospital Clínico Universitario Lozano Blesa

Zaragoza, , Spain

Site Status

Hospital Miguel Servet

Zaragoza, , Spain

Site Status

Countries

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Spain

References

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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.

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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.

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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.

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PMID: 38048552 (View on PubMed)

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.

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PMID: 38031761 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38023148 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37646661 (View on PubMed)

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.

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PMID: 35157768 (View on PubMed)

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.

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PMID: 34587246 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32693406 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31484647 (View on PubMed)

Other Identifiers

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GEM2012MENOS65

Identifier Type: -

Identifier Source: org_study_id