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

Multiple Myeloma Clinical Trial

— GEM2012MENOS65  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01916252
• Other study ID #: GEM2012MENOS65
• Status: Completed
• Phase: Phase 3
• First received: July 30, 2013
• Last updated: September 26, 2017
• Start date: September 2013
• Est. completion date: November 16, 2016

Study information

• Verified date: December 2016
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 460
• Est. completion date: November 16, 2016
• Est. primary completion date: November 16, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• bortezomib (Velcade ®)

• lenalidomide (Revlimid®)

• busulfan (Busilvex ®)

• Dexamethasone acetate

• Melphalan

Locations

Country	Name	City	State
Spain	Hospital General de Albacete	Albacete
Spain	Hospital Univ. Fundación de Alcorcón	Alcorcón
Spain	Hospital General Univ. de Alicante	Alicante
Spain	Hospital Torrevieja Salud UTE	Alicante
Spain	Hospital del Tajo	Aranjuez
Spain	Hospital German Trias i Pujol	Badalona
Spain	Hospital de Cruces	Barakaldo
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall d´Hebrón	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital San Pedro de Alcántara (Complejo Hospitalario de Cáceres)	Cáceres
Spain	Hospital General Univ. Santa Lucía	Cartagena
Spain	Hospital General de Castellón	Castellón
Spain	Hospital General de Ciudad Real	Ciudad Real
Spain	Hospital del Vinalopó	Elche
Spain	Hospital de Fuenlabrada	Fuenlabrada
Spain	Hospital de Cabueñes	Gijón
Spain	H. Univ. de Girona Dr. Josep Trueta (ICO)	Girona
Spain	Complejo Hosp. Virgen de las Nieves	Granada
Spain	Hospital Universitario de Guadalajara	Guadalajara
Spain	Hospital Esp. de Jerez de la Frontera	Jerez de la Frontera	Cádiz
Spain	Hospital Durán i Reynals - ICO L´Hospitalet	L'Hospitalet	Barcelona
Spain	Hospital Severo Ochoa	Leganés
Spain	Hospital de León	León
Spain	Hospital Universitari Arnau de Vilanova de Lleida	Lleida
Spain	Hospital San Pedro	Logroño
Spain	Centro Oncológico MD Anderson	Madrid
Spain	Fundación Jiménez Díaz-UTE	Madrid
Spain	Hospital Clínico Universitario San Carlos	Madrid
Spain	Hospital General Univ. Gregorio Marañón	Madrid
Spain	Hospital Infanta Cristina	Madrid
Spain	Hospital Infanta Leonor	Madrid
Spain	Hospital Infanta Sofía	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Madrid Sanchinarro	Madrid
Spain	Hospital Universitario Puerta de Hierro-Majadahonda	Majadahonda
Spain	Hospital Son Espases (Son Dureta)	Mallorca	Illes Balears
Spain	H. Althaia, Xarxa Asistencial de Manresa	Manresa	Barcelona
Spain	Complejo Hospitalario Costa del Sol	Marbella
Spain	Hospital Morales Meseguer	Murcia
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Complejo Hospitalario Ourense	Orense
Spain	Hospital Universitario Central Asturias	Oviedo
Spain	Hospital Son Llátzer	Palma de Mallorca	Illes Balears
Spain	Hospital de Gran Canaria Dr. Negrín	Palmas de Gran Canaria	Islas Canarias
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Complejo Hospitalario de Navarra (Hospital Virgen del Camino)	Pamplona
Spain	Complejo Hospitalario Pontevedra	Pontevedra
Spain	Hospital de Sabadell (Parc Taulí)	Sabadell
Spain	Hospital Clínico de Salamanca	Salamanca
Spain	Hospital Universitario de Donostia	San Sebastián
Spain	Hospital Univ. Marqués de	Santander
Spain	Complejo Universitario de Santiago	Santiago de Compostela
Spain	Hospital General de Segovia	Segovia
Spain	Complejo Hosp. Regional Virgen del Rocío	Sevilla
Spain	Hospital Nuestra Señora de Valme	Sevilla
Spain	Hospital Santa Bárbara	Soria
Spain	Hospital Nuestra Señora del Prado	Talavera de la Reina	Madrid
Spain	H. Universitari de Tarragona Joan XXIII	Tarragona
Spain	Hospital Universitari Mutua de Terrassa	Terrassa
Spain	Complejo Universitario de Toledo	Toledo	Madrid
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital Clínico de Valladolid	Valladolid
Spain	Hospital Universitario Río Hortega	Valladolid
Spain	Hospital de Txagorritxu	Vitoria
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (4)

Lead Sponsor	Collaborator
PETHEMA Foundation	Celgene, Janssen, LP, Pierre Fabre Medicament

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival to measure the treatment efficacy		2 years
Secondary	Complete response rates to measure the treatment efficacy		1 year
Secondary	Evaluation of minimal residual disease immunofixation negative-CR after each phase of treatment		1 year
Secondary	Overall survival		Time to death
Secondary	Describe the adverse events to evaluate the safety and tolerability		4 years