AzTrials
AzTrials

Multiple MyelomaPhase 3GEM2012MENOS65NCT01916252

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

A Phase 3 study testing bortezomib (Velcade ®), lenalidomide (Revlimid®) and busulfan (Busilvex ®) in people with Multiple Myeloma, run by PETHEMA Foundation at 74 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Multiple Myeloma
What is being tested?
bortezomib (Velcade ®), lenalidomide (Revlimid®) and busulfan (Busilvex ®)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
460 participants
Where
74 sitesSpain
Study dates
Sep 2013to 16 Nov 2016
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 13Show fewer
  • 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

Who cannot join

  • 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.

Trial locations and contacts

74 sites in 1 country.

74 sites in 1 country

Spain74 sites

  • Hospital General de Albacete

    Albacete, 02006

  • Hospital Univ. Fundación de Alcorcón

    Alcorcón

  • Hospital General Univ. de Alicante

    Alicante

  • Hospital Torrevieja Salud UTE

    Alicante

  • Hospital del Tajo

    Aranjuez

  • Hospital German Trias i Pujol

    Badalona

  • Hospital de Cruces

    Barakaldo

  • Hospital Clinic i Provincial de Barcelona

    Barcelona, 08036

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • Hospital del Mar

    Barcelona

  • Hospital Vall d´Hebrón

    Barcelona

  • Hospital Universitario de Burgos

    Burgos, 09006

  • Hospital San Pedro de Alcántara (Complejo Hospitalario de Cáceres)

    Cáceres

  • Hospital General Univ. Santa Lucía

    Cartagena

  • Hospital General de Castellón

    Castellon

  • Hospital General de Ciudad Real

    Ciudad Real, 13005

  • Hospital del Vinalopó

    Elche

  • Hospital de Fuenlabrada

    Fuenlabrada

  • Hospital de Cabueñes

    Gijón, 33394

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

    Girona

  • Complejo Hosp. Virgen de las Nieves

    Granada, 18014

  • Hospital Universitario de Guadalajara

    Guadalajara, 19002

  • Hospital Esp. de Jerez de la Frontera

    Jerez de la Frontera, Cádiz, 11407

  • Hospital Durán i Reynals - ICO L´Hospitalet

    L'Hospitalet de Llobregat, Barcelona, -08907

  • Hospital de Gran Canaria Dr. Negrín

    Las Palmas de Gran Canaria, Canary Islands, 35020

  • Hospital Severo Ochoa

    Leganés

  • Hospital de León

    León, 24071

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida

  • Hospital San Pedro

    Logroño

  • Centro Oncológico MD Anderson

    Madrid

  • Fundación Jiménez Díaz-UTE

    Madrid

  • Hospital Clínico Universitario San Carlos

    Madrid

  • Hospital General Univ. Gregorio Marañón

    Madrid

  • Hospital Infanta Cristina

    Madrid

  • Hospital Infanta Leonor

    Madrid

  • Hospital Infanta Sofía

    Madrid

  • Hospital Ramón y Cajal

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario de la Princesa

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Madrid Sanchinarro

    Madrid

  • Hospital Universitario Puerta de Hierro-Majadahonda

    Majadahonda

  • Hospital Son Espases (Son Dureta)

    Mallorca, Balearic Islands, 07010

  • H. Althaia, Xarxa Asistencial de Manresa

    Manresa, Barcelona, 08243

  • Complejo Hospitalario Costa del Sol

    Marbella, 29602

  • Hospital Morales Meseguer

    Murcia

  • Hospital Universitario Virgen de la Arrixaca

    Murcia

  • Complejo Hospitalario Ourense

    Ourense

  • Hospital Universitario Central Asturias

    Oviedo, 33006

  • Hospital Son Llátzer

    Palma de Mallorca, Balearic Islands, 07198

  • Clínica Universidad de Navarra

    Pamplona

  • Complejo Hospitalario de Navarra (Hospital Virgen del Camino)

    Pamplona

  • Complejo Hospitalario Pontevedra

    Pontevedra

  • Hospital de Sabadell (Parc Taulí)

    Sabadell

  • Hospital Clínico de Salamanca

    Salamanca, 37007

  • Hospital Universitario de Donostia

    San Sebastián

  • Hospital Univ. Marqués de

    Santander, 39008

  • Complejo Universitario de Santiago

    Santiago de Compostela

  • Hospital General de Segovia

    Segovia, 40002

  • Complejo Hosp. Regional Virgen del Rocío

    Seville, 41013

  • Hospital Nuestra Señora de Valme

    Seville, 41014

  • Hospital Santa Bárbara

    Soria, 42005

  • Hospital Nuestra Señora del Prado

    Talavera de La Reina, Madrid, 45600

  • H. Universitari de Tarragona Joan XXIII

    Tarragona

  • Hospital Universitari Mutua de Terrassa

    Terrassa

  • Complejo Universitario de Toledo

    Toledo, Madrid, 45004

  • Hospital Clínico Universitario de Valencia

    Valencia

  • Hospital Universitario Dr. Peset

    Valencia

  • Hospital Universitario La Fe

    Valencia

  • Hospital Clínico de Valladolid

    Valladolid, 47003

  • Hospital Universitario Río Hortega

    Valladolid, 47012

  • Hospital de Txagorritxu

    Vitoria-Gasteiz

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza, 50009

  • Hospital Miguel Servet

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: A Randomized, National, Open-label, Multicenter, Phase III Trial Studying Induction Therapy With Bortezomib/Lenalidomide/Dexamethasone (VRD-GEM), Followed by High-dose Chemotherapy With Melphalan-200 (MEL-200) Versus Busulfan-melphalan (BUMEL), and Consolidation With VRD-GEM in Patients Under 65 Years Old With Newly-diagnosed, Symptomatic Multiple Myeloma

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.

Read more

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

Being tested
bortezomib (Velcade ®), lenalidomide (Revlimid®), busulfan (Busilvex ®), Dexamethasone acetate, Melphalan
Keywords
Multiple Myeloma, MEL200, BUMEL
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bortezomib (Velcade ®)Drug

  • lenalidomide (Revlimid®)Drug

  • busulfan (Busilvex ®)Drug

  • Dexamethasone acetateDrug

  • MelphalanDrug

Study groups in NCT01916252
Study groupRoleWhat they receive
MEL-200Active comparatorbortezomib/lenalidomide/dexamethasone (VRD-GEM) induction treatment followed by high-dose melphalan-200 (MEL-200)
Receives: Drug: bortezomib (Velcade ®); Drug: lenalidomide (Revlimid®); Drug: Dexamethasone acetate; Drug: Melphalan
BUMELActive comparatorbortezomib/lenalidomide/dexamethasone (VRD-GEM) induction treatment followed by busulfan-melphalan (BUMEL) chemotherapy and consolidation with VRD-GEM
Receives: Drug: bortezomib (Velcade ®); Drug: lenalidomide (Revlimid®); Drug: busulfan (Busilvex ®); Drug: Dexamethasone acetate; Drug: Melphalan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival to measure the treatment efficacy

    Measured: 2 years

Secondary outcomes (4)

  1. Complete response rates to measure the treatment efficacy

    Measured: 1 year

  2. Evaluation of minimal residual disease immunofixation negative-CR after each phase of treatment

    Measured: 1 year

  3. Overall survival

    Measured: Time to death

  4. Describe the adverse events to evaluate the safety and tolerability

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2013 (estimated)
  2. Study startSep 2013
  3. Primary completion16 Nov 2016
  4. Study completion16 Nov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
460 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01916252
Sponsor's protocol ID
GEM2012MENOS65
Acronym
GEM2012MENOS65
Status last verified
Dec 2016
First submitted
30 Jul 2013
Last updated
27 Sep 2017
Results posted
No
Data monitoring committee
Yes

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.

    PubMed 40499010

  • 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.

    PubMed 39293025

  • 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.

    PubMed 38048552

  • 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.

    PubMed 38031761

  • 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.

    PubMed 38023148

  • 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.

    PubMed 37646661

  • 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.

    PubMed 35157768

  • 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.

    PubMed 34587246

  • 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.

    PubMed 32693406

  • 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.

    PubMed 31484647

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing bortezomib (Velcade ®), lenalidomide (Revlimid®) and busulfan (Busilvex ®) in people with Multiple Myeloma, run by PETHEMA Foundation at 74 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 74 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival to measure the treatment efficacy (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01916252, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in