Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) Versus Alternating Velcade/Melphalan/Prednisone (MPV) With Revlimid/Low Dose Dexamethasone

NCT01237249 | Completed Phase 2 DMC

• 1 other identifier: GEM2010MAS65
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 63

Brief Summary

This is a national, multicenter, open-label, randomized, comparative study designed to compare, first, the TTP of the two treatment schemes proposed (MPV followed by Rd or MPV alternating with Rd) in newly diagnosed MM patients older than 65 years. This comparison will be performing in terms of both efficacy and safety. Up to 120 patients will be included in each treatment arm and evaluated at scheduled visits in up to 3 study periods: Pre-treatment, Treatment and Follow-up. Primary outcome measure:

• To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years.
• To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd. Secondary outcome measure:
• To evaluate the response, duration of response, progression free survival (PFS), time to next therapy (TNT) and overall survival (OS) in the two different groups of patients.
• To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Velcade; Revlimid

Outcome Measures

Primary Outcomes (2)

• To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years.

  18 months

• To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd,in terms of adverse events presented in both groups of patients

  6 months

Secondary Outcomes (6)

• To evaluate the response in both groups of patients

  1 year

• To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments

  2 years

• Duration of response in two groups of patients

  2 years

• Progression free survival (PFS) in two different groups of patients

  18 months

• Time to next therapy (TNT)

  2 years

Study Arms (2)

MPV followed by Revlimid/Low Dose Dexamethasone (Rd)

ACTIVE COMPARATOR

Melphalan/Prednisone/Velcade (MPV) followed by Revlimid/Low Dose Dexamethasone (Rd)

Drug: Melphalan; Drug: Prednisone; Drug: Velcade

Alternating MPV with Revlimid/Low Dose Dexamethasone

EXPERIMENTAL

Alternating Velcade/Melphalan/Prednisone (MPV) with Revlimid/Low Dose Dexamethasone (Rd)

Drug: Revlimid; Drug: Dexamethasone

Interventions

Melphalan DRUG

MPV followed by Revlimid/Low Dose Dexamethasone (Rd)

Prednisone DRUG

MPV followed by Revlimid/Low Dose Dexamethasone (Rd)

Velcade DRUG

MPV followed by Revlimid/Low Dose Dexamethasone (Rd)

Revlimid DRUG

Alternating MPV with Revlimid/Low Dose Dexamethasone

Dexamethasone DRUG

Alternating MPV with Revlimid/Low Dose Dexamethasone

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Written informed consent obtained before starting any study-specific procedure.
• Symptomatic elderly MM newly diagnosed by EBMT criteria older than 65 years.
• Performance status (ECOG) ≤ 2.
• Have pre-treatment clinical laboratory values meeting the following criteria within 14 days of randomization:
• platelet count ≥ 75x109/L
• haemoglobin ≥ 8g/dL
• absolute neutrophil count (ANC) ≥ 1.0x109/L
• Serum bilirubin ≤ 1.5 mg/dL and alkaline phosphatise ≤ 2.5 x ULN AST, ALT ≤ 2.5 x ULN
• Serum creatinine ≤2,5 mg/dl

You may not qualify if:

• Patient previously received treatment with Velcade or Revlimid.
• Patient previously received treatment for Multiple Myeloma.
• Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrolment.
• Patient has hypersensitivity to bortezomib, boron, mannitol or lenalidomide.
• Patient has received other investigational drugs with 28 days before enrolment.
• Patient had a myocardial infarction within 6 months of enrolment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Patient currently is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
• Radiation therapy within 30 days before randomization, at least patient has had antialgic radiation. Radiation therapy will be afterwards permitted during the treatment period if it is indicated due to the presence of plasmacytomas

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Janssen-Cilag Ltd.: collaborator
• Celgene: collaborator
• TFS Trial Form Support: collaborator

Study Sites (63)

H. Son Llatzer

Palma de Mallorca, Balearic Islands, Spain

Location

H. Vall d'Hebron, Barcelona

Barcelona, Barcelona, Spain

Location

ICO - Duran i Reynals, Hospitalet de Llobregat

Barcelona, Barcelona, Spain

Location

Hospital General de Castellón

Castellon, Castellón, Spain

Location

Hospital Principe de Asturias

Alcalá de Henares, Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Navarre, Spain

Location

Hospital Joan XXIII

Tarragona, Tarragona, Spain

Location

Hospital Universitario Dr. Peset

Valencia, Valencia, Spain

Location

Miguel Servet

Zaragoza, Zaragoza, Spain

Location

Fundación Hospital Alcorcón

Alcorcón, Spain

Location

Hospital de Badalona Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital de Cruces

Bilbao, Spain

Location

Hospital Puerta del Mar

Cadiz, Spain

Location

Complejo Hospitalario de Cáceres

Cáceres, Spain

Location

Hospital General

Ciudad Real, Spain

Location

Hospital Virgen de la Luz

Cuenca, Spain

Location

Hospital Donostia

Donostia / San Sebastian, Spain

Location

Hospital Francesc Borja

Gandia, Spain

Location

ICO - Josep Trueta

Girona, Spain

Location

Hospital General de Guadalajara

Guadalajara, Spain

Location

H. de Jerez

Jerez de la Frontera, Spain

Location

Complejo Hospitalario León

León, Spain

Location

Clínica Puerta de Hierro

Madrid, Spain

Location

Hospital 12 de Octubre. Madrid

Madrid, Spain

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Hospital de Fuenlabrada

Madrid, Spain

Location

Hospital de la Princesa

Madrid, Spain

Location

Hospital de Madrid, S.A.- Norte Hospital General

Madrid, Spain

Location

Hospital del Tajo

Madrid, Spain

Location

Hospital Infanta Leonor

Madrid, Spain

Location

Hospital Infanta Sofia

Madrid, Spain

Location

Hospital la Paz

Madrid, Spain

Location

Hospital Severo Ochoa

Madrid, Spain

Location

Hospital Universitario Gregorio Marañón

Madrid, Spain

Location

MD Anderson

Madrid, Spain

Location

Althaia

Manresa, Spain

Location

Complejo Hospital Costa del Sol

Málaga, Spain

Location

Hospital Nuestra Señora de Valme

Málaga, Spain

Location

Hospital General Univeristario Morales Messeguer

Murcia, Spain

Location

Hospital Virgen de la Arrixaca

Murcia, Spain

Location

Hospital de la Diputación de Navarra

Navarra, Spain

Location

Hospital de Gran Canaria Doctor Negrín

Palma de Gran Canaria, Spain

Location

Complejo Asistencial Son Dureta

Palma de Mallorca, Spain

Location

Hospital Virgen del Camino

Pamplona, Spain

Location

Corporació Sanitaria Parc Taulí

Sabadell, Spain

Location

Hospital Clínico de Salamanca

Salamanca, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hoaspital Marqués de Valdecilla

Santander, Spain

Location

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain

Location

Hospital General de Segovia

Segovia, Spain

Location

Complejo Hospitalario Regional Virgen del Rocío

Seville, Spain

Location

Hospital Nuestra Señora del Prado

Toledo, Spain

Location

Hospital Virgen de la Salud

Toledo, Spain

Location

Hospital Arnau de Vilanova

Valencia, Spain

Location

Hospital Clínico de Valencia.

Valencia, Spain

Location

Hospital La Fe

Valencia, Spain

Location

Hospital Txagorritxu

Vitoria-Gasteiz, Spain

Location

Hospital Virgen de la Concha

Zamora, Spain

Location

Hospital Clinico Lozano Blesa

Zaragoza, Spain

Location

Related Publications (3)

• Quwaider D, Corchete LA, Misiewicz-Krzeminska I, Sarasquete ME, Perez JJ, Krzeminski P, Puig N, Mateos MV, Garcia-Sanz R, Herrero AB, Gutierrez NC. DEPTOR maintains plasma cell differentiation and favorably affects prognosis in multiple myeloma. J Hematol Oncol. 2017 Apr 18;10(1):92. doi: 10.1186/s13045-017-0461-8.

  PMID: 28420429 DERIVED

• Paiva B, Cedena MT, Puig N, Arana P, Vidriales MB, Cordon L, Flores-Montero J, Gutierrez NC, Martin-Ramos ML, Martinez-Lopez J, Ocio EM, Hernandez MT, Teruel AI, Rosinol L, Echeveste MA, Martinez R, Gironella M, Oriol A, Cabrera C, Martin J, Bargay J, Encinas C, Gonzalez Y, Van Dongen JJ, Orfao A, Blade J, Mateos MV, Lahuerta JJ, San Miguel JF; Grupo Espanol de Mieloma/Programa para el Estudio de la Terapeutica en Hemopatias Malignas (GEM/PETHEMA) Cooperative Study Groups. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients. Blood. 2016 Jun 23;127(25):3165-74. doi: 10.1182/blood-2016-03-705319. Epub 2016 Apr 26.

  PMID: 27118453 DERIVED

• Paiva B, Corchete LA, Vidriales MB, Puig N, Maiso P, Rodriguez I, Alignani D, Burgos L, Sanchez ML, Barcena P, Echeveste MA, Hernandez MT, Garcia-Sanz R, Ocio EM, Oriol A, Gironella M, Palomera L, De Arriba F, Gonzalez Y, Johnson SK, Epstein J, Barlogie B, Lahuerta JJ, Blade J, Orfao A, Mateos MV, San Miguel JF; Spanish Myeloma Group / Program for the Study of Malignant Blood Diseases Therapeutics (GEM / PETHEMA) Cooperative Study Groups. Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance. Blood. 2016 Apr 14;127(15):1896-906. doi: 10.1182/blood-2015-08-665679. Epub 2016 Jan 11.

  PMID: 26755711 DERIVED

Related Links

• Spanish Association of Hematology

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Prednisone; Bortezomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2010
• First Posted: November 9, 2010
• Study Start: February 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: May 1, 2016
• Last Updated: January 18, 2017

Record last verified: 2017-01

Locations

ES (63)