Clinical trial NCT01916252: Bortezomib (Velcade®), Lenalidomide (Revlimid®) and IV Busulfan (Busilvex®) in Patients Under 65 Years Old
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
MEL200
BUMEL
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
Collaborators: name: Janssen, LP
name: Celgene
name: Pierre Fabre Medicament
First posted: 2013-08-05
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival to measure the treatment efficacy
timeFrame: 2 years
Secondary outcomes:
measure: Complete response rates to measure the treatment efficacy
timeFrame: 1 year
measure: Evaluation of minimal residual disease immunofixation negative-CR after each phase of treatment
timeFrame: 1 year
measure: Overall survival
timeFrame: Time to death
measure: Describe the adverse events to evaluate the safety and tolerability
timeFrame: 4 years
Other outcomes:
Locations:
city: L'Hospitalet
country: Spain
facility: Hospital Durán i Reynals - ICO L´Hospitalet
state: Barcelona
city: Manresa
country: Spain
facility: H. Althaia, Xarxa Asistencial de Manresa
state: Barcelona
city: Jerez de la Frontera
country: Spain
facility: Hospital Esp. de Jerez de la Frontera
state: Cádiz
city: Mallorca
country: Spain
facility: Hospital Son Espases (Son Dureta)
state: Illes Balears
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llátzer
state: Illes Balears
city: Palmas de Gran Canaria
country: Spain
facility: Hospital de Gran Canaria Dr. Negrín
state: Islas Canarias
city: Talavera de la Reina
country: Spain
facility: Hospital Nuestra Señora del Prado
state: Madrid
city: Toledo
country: Spain
facility: Complejo Universitario de Toledo
state: Madrid
city: Albacete
country: Spain
facility: Hospital General de Albacete
city: Alcorcón
country: Spain
facility: Hospital Univ. Fundación de Alcorcón
city: Alicante
country: Spain
facility: Hospital General Univ. de Alicante
city: Alicante
country: Spain
facility: Hospital Torrevieja Salud UTE
city: Aranjuez
country: Spain
facility: Hospital del Tajo
city: Badalona
country: Spain
facility: Hospital German Trias i Pujol
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebrón
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Cartagena
country: Spain
facility: Hospital General Univ. Santa Lucía
city: Castellón
country: Spain
facility: Hospital General de Castellón
city: Ciudad Real
country: Spain
facility: Hospital General de Ciudad Real
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara (Complejo Hospitalario de Cáceres)
city: Elche
country: Spain
facility: Hospital del Vinalopó
city: Fuenlabrada
country: Spain
facility: Hospital de Fuenlabrada
city: Gijón
country: Spain
facility: Hospital de Cabueñes
city: Girona
country: Spain
facility: H. Univ. de Girona Dr. Josep Trueta (ICO)
city: Granada
country: Spain
facility: Complejo Hosp. Virgen de las Nieves
city: Guadalajara
country: Spain
facility: Hospital Universitario de Guadalajara
city: Leganés
country: Spain
facility: Hospital Severo Ochoa
city: León
country: Spain
facility: Hospital de León
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida
city: Logroño
country: Spain
facility: Hospital San Pedro
city: Madrid
country: Spain
facility: Centro Oncológico MD Anderson
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz-UTE
city: Madrid
country: Spain
facility: Hospital Clínico Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital General Univ. Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Infanta Cristina
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Infanta Sofía
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
city: Marbella
country: Spain
facility: Complejo Hospitalario Costa del Sol
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Orense
country: Spain
facility: Complejo Hospitalario Ourense
city: Oviedo
country: Spain
facility: Hospital Universitario Central Asturias
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra (Hospital Virgen del Camino)
city: Pontevedra
country: Spain
facility: Complejo Hospitalario Pontevedra
city: Sabadell
country: Spain
facility: Hospital de Sabadell (Parc Taulí)
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
city: San Sebastián
country: Spain
facility: Hospital Universitario de Donostia
city: Santander
country: Spain
facility: Hospital Univ. Marqués de
city: Santiago de Compostela
country: Spain
facility: Complejo Universitario de Santiago
city: Segovia
country: Spain
facility: Hospital General de Segovia
city: Sevilla
country: Spain
facility: Complejo Hosp. Regional Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Nuestra Señora de Valme
city: Soria
country: Spain
facility: Hospital Santa Bárbara
city: Tarragona
country: Spain
facility: H. Universitari de Tarragona Joan XXIII
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua de Terrassa
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico de Valladolid
city: Valladolid
country: Spain
facility: Hospital Universitario Río Hortega
city: Vitoria
country: Spain
facility: Hospital de Txagorritxu
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.