Bortezomib (Velcade®), Lenalidomide (Revlimid®) and IV Busulfan (Busilvex®) in Patients Under 65 Years Old (GEM2012MENOS65)

September 26, 2017 updated by: PETHEMA Foundation

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.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

460

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Albacete, Spain, 02006
        • Hospital General de Albacete
      • Alcorcón, Spain
        • Hospital Univ. Fundación de Alcorcón
      • Alicante, Spain
        • Hospital General Univ. de Alicante
      • Alicante, Spain
        • Hospital Torrevieja Salud UTE
      • Aranjuez, Spain
        • Hospital del Tajo
      • Badalona, Spain
        • Hospital German Trias i Pujol
      • Barakaldo, Spain
        • Hospital de Cruces
      • Barcelona, Spain
        • Hospital del Mar
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08036
        • Hospital Clinic i Provincial de Barcelona
      • Barcelona, Spain
        • Hospital Vall d´hebron
      • Burgos, Spain, 09006
        • Hospital Universitario de Burgos
      • Cartagena, Spain
        • Hospital General Univ. Santa Lucía
      • Castellón, Spain
        • Hospital General de Castellon
      • Ciudad Real, Spain, 13005
        • Hospital General de Ciudad Real
      • Cáceres, Spain
        • Hospital San Pedro de Alcántara (Complejo Hospitalario de Cáceres)
      • Elche, Spain
        • Hospital del Vinalopó
      • Fuenlabrada, Spain
        • Hospital De Fuenlabrada
      • Gijón, Spain, 33394
        • Hospital de Cabueñes
      • Girona, Spain
        • H. Univ. de Girona Dr. Josep Trueta (ICO)
      • Granada, Spain, 18014
        • Complejo Hosp. Virgen de las Nieves
      • Guadalajara, Spain, 19002
        • Hospital Universitario de Guadalajara
      • Leganés, Spain
        • Hospital Severo Ochoa
      • León, Spain, 24071
        • Hospital de Leon
      • Lleida, Spain
        • Hospital Universitari Arnau de Vilanova de Lleida
      • Logroño, Spain
        • Hospital San Pedro
      • Madrid, Spain
        • Hospital Ramón y Cajal
      • Madrid, Spain
        • Hospital Clínico Universitario San Carlos
      • Madrid, Spain
        • Hospital Universitario 12 de octubre
      • Madrid, Spain
        • Hospital Universitario La Paz
      • Madrid, Spain
        • Hospital Universitario de La Princesa
      • Madrid, Spain
        • Hospital Infanta Leonor
      • Madrid, Spain
        • Centro Oncológico MD Anderson
      • Madrid, Spain
        • Fundacion Jimenez Diaz-UTE
      • Madrid, Spain
        • Hospital General Univ. Gregorio Maranon
      • Madrid, Spain
        • Hospital Infanta Cristina
      • Madrid, Spain
        • Hospital Infanta Sofia
      • Madrid, Spain
        • Hospital Universitario Madrid Sanchinarro
      • Majadahonda, Spain
        • Hospital Universitario Puerta de Hierro-Majadahonda
      • Marbella, Spain, 29602
        • Complejo Hospitalario Costa del Sol
      • Murcia, Spain
        • Hospital Universitario Virgen de la Arrixaca
      • Murcia, Spain
        • Hospital Morales Meseguer
      • Orense, Spain
        • Complejo Hospitalario Ourense
      • Oviedo, Spain, 33006
        • Hospital Universitario Central Asturias
      • Pamplona, Spain
        • Clinica Universidad de Navarra
      • Pamplona, Spain
        • Complejo Hospitalario de Navarra (Hospital Virgen del Camino)
      • Pontevedra, Spain
        • Complejo Hospitalario Pontevedra
      • Sabadell, Spain
        • Hospital de Sabadell (Parc Taulí)
      • Salamanca, Spain, 37007
        • Hospital Clinico De Salamanca
      • San Sebastián, Spain
        • Hospital Universitario de Donostia
      • Santander, Spain, 39008
        • Hospital Univ. Marqués de
      • Santiago de Compostela, Spain
        • Complejo Universitario de Santiago
      • Segovia, Spain, 40002
        • Hospital General de Segovia
      • Sevilla, Spain, 41014
        • Hospital Nuestra Señora de Valme
      • Sevilla, Spain, 41013
        • Complejo Hosp. Regional Virgen del Rocío
      • Soria, Spain, 42005
        • Hospital Santa Bárbara
      • Tarragona, Spain
        • H. Universitari de Tarragona Joan XXIII
      • Terrassa, Spain
        • Hospital Universitari Mutua de Terrassa
      • Valencia, Spain
        • Hospital Clinico Universitario de Valencia
      • Valencia, Spain
        • Hospital Universitario Dr. Peset
      • Valencia, Spain
        • Hospital Universitario La Fe
      • Valladolid, Spain, 47012
        • Hospital Universitario Río Hortega
      • Valladolid, Spain, 47003
        • Hospital Clínico de Valladolid
      • Vitoria, Spain
        • Hospital de Txagorritxu
      • Zaragoza, Spain, 50009
        • Hospital Clinico Universitario Lozano Blesa
      • Zaragoza, Spain, 50009
        • Hospital Miguel Servet
    • Barcelona
      • L'Hospitalet, Barcelona, Spain, -08907
        • Hospital Durán i Reynals - ICO L´Hospitalet
      • Manresa, Barcelona, Spain, 08243
        • H. Althaia, Xarxa Asistencial de Manresa
    • Cádiz
      • Jerez de la Frontera, Cádiz, Spain, 11407
        • Hospital Esp. de Jerez de la Frontera
    • Illes Balears
      • Mallorca, Illes Balears, Spain, 07010
        • Hospital Son Espases (Son Dureta)
      • Palma de Mallorca, Illes Balears, Spain, 07198
        • Hospital Son Llatzer
    • Islas Canarias
      • Palmas de Gran Canaria, Islas Canarias, Spain, 35020
        • Hospital De Gran Canaria Dr. Negrin
    • Madrid
      • Talavera de la Reina, Madrid, Spain, 45600
        • Hospital Nuestra Señora del Prado
      • Toledo, Madrid, Spain, 45004
        • Complejo Universitario de Toledo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: MEL-200
bortezomib/lenalidomide/dexamethasone (VRD-GEM) induction treatment followed by high-dose melphalan-200 (MEL-200)
Drug: Melphalan
Drug: bortezomib (Velcade ®)
Drug: lenalidomide (Revlimid®)
Drug: Dexamethasone acetate
Active Comparator: BUMEL
bortezomib/lenalidomide/dexamethasone (VRD-GEM) induction treatment followed by busulfan-melphalan (BUMEL) chemotherapy and consolidation with VRD-GEM
Drug: Melphalan
Drug: bortezomib (Velcade ®)
Drug: lenalidomide (Revlimid®)
Drug: Dexamethasone acetate
Drug: busulfan (Busilvex ®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival to measure the treatment efficacy
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Complete response rates to measure the treatment efficacy
Time Frame: 1 year
1 year
Evaluation of minimal residual disease immunofixation negative-CR after each phase of treatment
Time Frame: 1 year
1 year
Overall survival
Time Frame: Time to death
Time to death
Describe the adverse events to evaluate the safety and tolerability
Time Frame: 4 years
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PETHEMA Foundation

Collaborators

Celgene
Pierre Fabre Medicament
Janssen, LP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

November 16, 2016

Study Completion (Actual)

November 16, 2016

Study Registration Dates

First Submitted

July 30, 2013

First Submitted That Met QC Criteria

August 1, 2013

First Posted (Estimate)

August 5, 2013

Study Record Updates

Last Update Posted (Actual)

September 27, 2017

Last Update Submitted That Met QC Criteria

September 26, 2017

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEM2012MENOS65

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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