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
A National, Open-label, Multicenter, Randomized, Comparative Phase IIb 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 (Rd).
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
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
The Pre-treatment period includes Screening visit. After providing written informed consent form to participate in the study, patients will be evaluated for eligibility during a screening period of 14 days (Days -14 to -1). If patients meet all inclusion and exclusion criteria will be randomized at the moment of entry in the trial in a 1:1 allocation to receive either MPV followed by Rd (Treatment Group A) or MPV alternating with Rd (Treatment Group B).
Patients in the Treatment Group A will receive nine cycles of MPV consisting on one 6-weeks cycle of Velcade (Bortezomib) as an intravenous bolus twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32) followed by a 10 day rest period (day 33 to 42), in combination with oral Melphalan, once daily on days 1 to 4 and oral Prednisone, once daily on days 1 to 4, followed by eight 4-weeks cycles of Velcade (Bortezomib) as an intravenous bolus on days 1, 8, 15 and 22 followed by a 6 day rest period (days 23 to 28), in combination with Melphalan and Prednisone per os once daily on days 1 to 4, followed by a 24-day rest period (days 5 to 28). After the nine MPV cycles, patients will receive nine cycles of Rd consisting on 4-weeks cycles, including Revlimid (lenalidomide), once daily on days 1-21 followed by a 7 day rest period (days 22 to 28) plus oral dexamethasone, once weekly on days 1,8,15 and 22, followed by a 6 day rest period (days 23 to 28).
Patients in the Treatment Group B will receive the same schedule of therapy, but the MPV cycles will be alternated with Rd cycles. In this treatment Group B, patients will be again randomized to start receiving either MPV or Rd as first cycle of therapy. Overall, patients will receive an identical number of cycles, nine cycles of MPV and nine of Rd. Patients randomized to Treatment Group A relapsing/progressing or with major toxicities under treatment with MPV will be crossover to receive Rd, but only after study coordinator approval.
During the Treatment Period, patients will be evaluated at day 1 of each cycle. After completion of the Treatment Period, all patients will be evaluated every 2 months thereafter.
Safety will be assessed by the monitoring of adverse events, physical examinations, vital signs measurements, and haematology and clinical chemistry test. Response to treatment will be based on EBMT an IMWG criteria. Response to treatment will be evaluated at day 1 of each induction cycle, and every 2 months during thereafter.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Alcorcón, Spanje
- Fundacion Hospital Alcorcon
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Badalona, Spanje
- Hospital de Badalona Germans Trias i Pujol
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Barcelona, Spanje
- Hospital Del Mar
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Barcelona, Spanje
- Hospital de La Santa Creu i Sant Pau
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Barcelona, Spanje
- Hospital Clinic i Provincial de Barcelona
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Barcelona, Spanje
- H. Vall d'Hebron, Barcelona
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Barcelona, Spanje
- ICO - Duran i Reynals, Hospitalet de Llobregat
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Bilbao, Spanje
- Hospital De Cruces
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Castellón, Spanje
- Hospital General de Castellon
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Ciudad Real, Spanje
- Hospital General
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Cuenca, Spanje
- Hospital Virgen de La Luz
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Cáceres, Spanje
- Complejo Hospitalario de Cáceres
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Cádiz, Spanje
- Hospital Puerta del Mar
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Donostia, Spanje
- Hospital Donostia
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Gandía, Spanje
- Hospital Francesc Borja
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Girona, Spanje
- ICO - Josep Trueta
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Guadalajara, Spanje
- Hospital General de Guadalajara
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Jerez de la Frontera, Spanje
- H. de Jerez
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Leon, Spanje
- Complejo Hospitalario León
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Madrid, Spanje
- Hospital Ramon y Cajal
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Madrid, Spanje
- Hospital La Paz
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Madrid, Spanje
- Hospital Clinico San Carlos
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Madrid, Spanje
- Hospital De Fuenlabrada
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Madrid, Spanje
- Hospital Infanta Leonor
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Madrid, Spanje
- Hospital de La Princesa
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Madrid, Spanje
- Hospital del Tajo
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Madrid, Spanje
- Hospital Universitario Gregorio Marañón
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Madrid, Spanje
- Hospital Severo Ochoa
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Madrid, Spanje
- Hospital Infanta Sofía
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Madrid, Spanje
- Clínica Puerta de Hierro
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Madrid, Spanje
- Hospital 12 de Octubre. Madrid
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Madrid, Spanje
- Hospital de Madrid, S.A.- Norte Hospital General
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Madrid, Spanje
- MD Anderson
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Manresa, Spanje
- Althaia
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Murcia, Spanje
- Hospital Virgen de la Arrixaca
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Murcia, Spanje
- Hospital General Univeristario Morales Messeguer
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Málaga, Spanje
- Complejo Hospital Costa Del Sol
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Málaga, Spanje
- Hospital Nuestra Senora de Valme
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Navarra, Spanje
- Hospital de la Diputación de Navarra
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Palma de Gran Canaria, Spanje
- Hospital de Gran Canaria Doctor Negrín
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Palma de Mallorca, Spanje
- Complejo Asistencial Son Dureta
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Pamplona, Spanje
- Hospital Virgen del Camino
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Sabadell, Spanje
- Corporacio Sanitaria Parc Tauli
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Salamanca, Spanje
- Hospital Clínico de Salamanca
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Santander, Spanje
- Hoaspital Marqués de Valdecilla
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Santiago de Compostela, Spanje
- Complejo Hospitalario Universitario de Santiago
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Segovia, Spanje
- Hospital General de Segovia
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Sevilla, Spanje
- Complejo Hospitalario Regional Virgen Del Rocío
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Tarragona, Spanje
- Hospital Joan XXIII
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Tenerife, Spanje
- Hospital Universitario de Canarias
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Toledo, Spanje
- Hospital Virgen de la Salud
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Toledo, Spanje
- Hospital Nuestra Señora del Prado
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Valencia, Spanje
- Hospital Arnau de Vilanova
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Valencia, Spanje
- Hospital Universitario Dr. Peset
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Valencia, Spanje
- Hospital La Fe
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Valencia, Spanje
- Hospital Clínico de Valencia.
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Vitoria, Spanje
- Hospital Txagorritxu
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Zamora, Spanje
- Hospital Virgen de la Concha
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Zaragoza, Spanje
- Hospital Clinico Lozano Blesa
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Zaragoza, Spanje
- Miguel Servet
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Baleares
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Palma de Mallorca, Baleares, Spanje
- H. Son Llatzer
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Madrid
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Alcalá de Henares, Madrid, Spanje
- Hospital Principe de Asturias
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Navarra
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Pamplona, Navarra, Spanje
- Clinica Universitaria de Navarra
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Actieve vergelijker: MPV followed by Revlimid/Low Dose Dexamethasone (Rd)
Melphalan/Prednisone/Velcade (MPV) followed by Revlimid/Low Dose Dexamethasone (Rd)
|
|
|
Experimenteel: Alternating MPV with Revlimid/Low Dose Dexamethasone
Alternating Velcade/Melphalan/Prednisone (MPV) with Revlimid/Low Dose Dexamethasone (Rd)
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
|
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.
Tijdsspanne: 18 months
|
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
Tijdsspanne: 6 months
|
6 months
|
Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
|
To evaluate the response in both groups of patients
Tijdsspanne: 1 year
|
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
Tijdsspanne: 2 years
|
2 years
|
|
Duration of response in two groups of patients
Tijdsspanne: 2 years
|
2 years
|
|
Progression free survival (PFS) in two different groups of patients
Tijdsspanne: 18 months
|
18 months
|
|
Time to next therapy (TNT)
Tijdsspanne: 2 years
|
2 years
|
|
Overall survival (OS) in the two different groups of patients
Tijdsspanne: 5 years
|
5 years
|
Medewerkers en onderzoekers
Sponsor
Publicaties en nuttige links
Algemene publicaties
- 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.
- 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.
- 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.
Nuttige links
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Hart-en vaatziekten
- Vaatziekten
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Immunoproliferatieve aandoeningen
- Hematologische ziekten
- Hemorragische aandoeningen
- Hemostatische aandoeningen
- Paraproteïnemieën
- Bloed eiwit stoornissen
- Multipel myeloom
- Neoplasmata, plasmacel
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Autonome agenten
- Agenten van het perifere zenuwstelsel
- Ontstekingsremmende middelen
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Anti-emetica
- Gastro-intestinale middelen
- Glucocorticoïden
- Hormonen
- Hormonen, hormoonvervangers en hormoonantagonisten
- Antineoplastische middelen, hormonaal
- Antineoplastische middelen, alkylering
- Alkyleringsmiddelen
- Myeloablatieve agonisten
- Angiogenese-remmers
- Angiogenese modulerende middelen
- Groei stoffen
- Groeiremmers
- Dexamethason
- Lenalidomide
- Prednison
- Melfalan
- Bortezomib
Andere studie-ID-nummers
- GEM2010MAS65
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