Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Drug: Bortezomib, Melphalan, Prednisone (VMP)Drug: 1 or 2 cycle(s) HDM (High Dose Melphalan)
- Registration Number
- NCT01208766
- Lead Sponsor
- Stichting Hemato-Oncologie voor Volwassenen Nederland
- Brief Summary
Study phase: phase III
Study objective:
* Comparison of Bortezomib, Melphalan, Prednisone (VMP) with High Dose Melphalan followed autologous stem cell transplantation (ASCT)
* Comparison of Bortezomib, Lenalidomide, Dexamethasone(VRD) as consolidation versus no consolidation
* Comparison of single versus tandem high dose Melphalan with ASCT
Patient population: Patients with symptomatic multiple myeloma,previously untreated, ISS stages 1-3, age 18-65 years inclusive
Study design: Prospective, multicenter, intergroup, randomized
Duration of treatment: Expected duration of induction, stem cell collection and intensification is 6 - 9 months. Consolidation with VRD will last 2 months Maintenance therapy with Lenalidomide will be given until relapse. All patients will be followed until 10 years after registration.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1503
- Patients with a confirmed diagnosis of symptomatic multiple myeloma stage I to III according to the International Staging System ISS (see appendix A), i.e. at least one of the CRAB criteria should be present;
- Measurable disease as defined by the presence of M-protein in serum or urine (serum M-protein> 10 g/l or urine M-protein > 200 mg/24 hours), or abnormal free light chain ratio;
- Age 18-65 years inclusive;
- WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by comorbid conditions);
- Negative pregnancy test at inclusion if applicable;
- Written informed consent.
Inclusion for randomisation 1:
- WHO performance 0-2;
- Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- A suitable stem cell graft containing at least 4 x 106 CD34+ cells/kg (or according to national guidelines).
Inclusion for randomisation 2:
- Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- ANC >= 0.5 x 109/l and platelets > 20 x 10^9/l;
- Patient is able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan.
- Known intolerance of Boron;
- Systemic AL amyloidosis;
- Primary Plasmacell Leukemia;
- Non-secretory MM;
- Previous chemotherapy or radiotherapy except local radiotherapy in case of local myeloma progression or corticosteroids maximum 5 days for symptom control;
- Severe cardiac dysfunction (NYHA classification II-IV);
- Significant hepatic dysfunction, unless related to myeloma;
- Patients with GFR <15 ml/min,
- Patients known to be HIV-positive;
- Patients with active, uncontrolled infections;
- Patients with neuropathy, CTC grade 2 or higher;
- Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
- Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women);
- Lactating women.
Exclusion for randomisation 1:
- Severe pulmonary, neurologic, or psychiatric disease;
- CTCAE grade 3-4 polyneuropathy during Bortezomib treatment;
- Allogeneic Stem Cell Transplantation (Allo SCT) planned;
- Progressive disease.'
Exclusion for randomisation 2:
- Progressive disease;
- Neuropathy, except CTCAE grade 1;
- CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description R1: 4 cycles Bortezomib, Melphalan, Prednisone (VMP) Bortezomib, Melphalan, Prednisone (VMP) All patients randomized to VMP treatment, will be treated with Bortezomib, Melphalan, Prednisone(VMP, 4 cycles) and will start intensification with VMP between 4 and 6 weeks after stem cell collection. R1: 1 (2) cycle(s) HDM 1 or 2 cycle(s) HDM (High Dose Melphalan) All patients randomized to intensification with High Dose Melphalan will start intensification with HDM (in hospitals with a policy of double intensification, patients will be randomized between VMP, 1 HDM and 2 HDM) between 4 and 6 weeks after stem cell collection. R2: 2 cycles of VRD 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD) In patients randomized to consolidation treatment, 2 cycles of Bortezomib, Lenalidomide,Dexamethasone (VRD) will start at 8 weeks after the end of the last course of VMP or HDM.
- Primary Outcome Measures
Name Time Method For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first end of trial (last patient last visit) For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first
For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause (whichever occurs first). end of trial (last patient last visit) For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause (whichever occurs first).
For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first end of trial (last patient last visit) For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first
- Secondary Outcome Measures
Name Time Method Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment. end of trial (last patient last visit) Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment.
Overall survival measured from the time of registration /randomization R1/ randomization R2. Patients still alive or lost to follow up are censored at the date they were last known to be alive. end of trial (last patient last visit) Overall survival measured from the time of registration /randomization R1/ randomization R2.
Patients still alive or lost to follow up are censored at the date they were last known to be alive.Toxicity End of trial (last patient last visit) Toxicity
Trial Locations
- Locations (208)
NL-Den Haag-HAGA
🇳🇱Den Haag, Netherlands
NL-Leiden-LUMC
🇳🇱Leiden, Netherlands
AT-Vienna-HANUSCH
🇦🇹Vienna, Austria
BE-Haine-Saint-Paul-JOLIMONT
🇧🇪Haine-Saint-Paul, Belgium
CHU Tivoli
🇧🇪La Louvière, Belgium
BE-Roeselare-AZDELTA
🇧🇪Roeselare, Belgium
SS Antonio e Biogio
🇮🇹Alessandria, Italy
AOU Umberto I-Clinica di Ematologica
🇮🇹Ancona, Italy
Policlinico di Bari
🇮🇹Bari, Italy
BE-Liege-CHRCITADELLE
🇧🇪Liège, Belgium
CHR Saint Joseph
🇧🇪Mons, Belgium
CH Wapi
🇧🇪Tournai, Belgium
Szeged University Hospital
ðŸ‡ðŸ‡ºSzeged, Hungary
St. Istvan and St. Laszlo Korhaz Hospital
ðŸ‡ðŸ‡ºBudapest, Hungary
GR-Athens-ALEXANDRA
🇬🇷Athens, Greece
Ospedale C. e G. Mazzoni-Ematologia
🇮🇹Ascoli Piceno, Italy
A.O.R.N. San G. Moscati
🇮🇹Avellino, Italy
Oaspedali Riuniti_Div di Ematologia
🇮🇹Bergamo, Italy
Instituto di Ematologia e Oncologia Medica
🇮🇹Bologna, Italy
Ospedale Generale Regionale_Div di Ema e Centro
🇮🇹Bolzano, Italy
Spedali Civili_U.O.Ematologia
🇮🇹Brescia, Italy
Pres Osp Di Summa
🇮🇹Brindisi, Italy
Ospedale Ferrarotto-Ema
🇮🇹Catania, Italy
Presidio Osp R. Binaghi
🇮🇹Cagliari, Italy
Inst per la Ricerca e la Cura del Cancro Di
🇮🇹Candiolo, Italy
Presidio ospedaliero dell'annunziata
🇮🇹Cosenza, Italy
Azienda Ospedaliera Universitaria S. Martino_Ematologia 2
🇮🇹Genova, Italy
Università La Sapienza Polo Pontino
🇮🇹Latina, Italy
ASUR Regione Marche
🇮🇹Marche, Italy
IRST
🇮🇹Meldola, Italy
Policlinico- servizio di Ematologia
🇮🇹Modena, Italy
Ospedale Cardarelli-Sezione di Ematologia TERE
🇮🇹Napoli, Italy
Università Amedeo Avogrado-Ospedale Maggiore
🇮🇹Novara, Italy
Istituto Nazionale dei Tumori-Ema
🇮🇹Milano, Italy
OspedaleCivico S Croce e carle
🇮🇹Cuneo, Italy
Ospedali Riuniti di Foggia
🇮🇹Foggia, Italy
Azienda Ospedaliera San Antonio Abate
🇮🇹Gallarate, Italy
Azienda Ospedaliera Universitaria S. Martino_Clinica Ematologica
🇮🇹Genova, Italy
Azienda Ospedaliera Universitaria S. Martino_Ematologia 1
🇮🇹Genova, Italy
Ospedale A. Manzoni
🇮🇹Lecco, Italy
Ospedale Niguarda CÃ Grande
🇮🇹Milano, Italy
Ospedale Cardarelli-ematologia e Trapianto di Midollo Osseo
🇮🇹Napoli, Italy
Ospedale San Francesco
🇮🇹Nuoro, Italy
Giaccone di Palermo
🇮🇹Palermo, Italy
Azienda Ospedaliera Papardo
🇮🇹Messina, Italy
Policlinico Gaetano Martino
🇮🇹Messina, Italy
Osp Dell Angelo
🇮🇹Mestre, Italy
Osp San Luigi Gonzaga-Pat med
🇮🇹Orbassano, Italy
Universita Federico II-Ema
🇮🇹Napoli, Italy
Ospedaliera di Pavona_Ematologia e
🇮🇹Padova, Italy
Ospedale Infermi
🇮🇹Rimini, Italy
Azienda Osp S. Andrea
🇮🇹Roma, Italy
Policlinico San Matteo
🇮🇹Pavia, Italy
NL-Maastricht-MUMC
🇳🇱Maastricht, Netherlands
NL-Nijmegen-RADBOUDUMC
🇳🇱Nijmegen, Netherlands
NL-Doetinchem-SLINGELAND
🇳🇱Doetinchem, Netherlands
NL-Dordrecht-ASZ
🇳🇱Dordrecht, Netherlands
NL-Geldrop-STANNA
🇳🇱Geldrop, Netherlands
NL-Gorinchem-BEATRIX
🇳🇱Gorinchem, Netherlands
NL-Hilversum-TERGOOI
🇳🇱Hilversum, Netherlands
NL-Hoorn-DIJKLANDERHOORN
🇳🇱Hoorn, Netherlands
NL-Rotterdam-ERASMUSMC
🇳🇱Rotterdam, Netherlands
NL-Rotterdam-IKAZIA
🇳🇱Rotterdam, Netherlands
NL-Heerlen-ATRIUMMC
🇳🇱Heerlen, Netherlands
NL-Rotterdam-EMCDANIEL
🇳🇱Rotterdam, Netherlands
NL-Tilburg-ETZ
🇳🇱Tilburg, Netherlands
NO-Trondheim-STOLAV
🇳🇴Trondheim, Norway
NL-Terneuzen-ZORGSAAM
🇳🇱Terneuzen, Netherlands
Gazi University Hospital
🇹🇷Ankara, Turkey
CH-Bern-INSEL
🇨ðŸ‡Bern, Switzerland
CH-Zürich-USZ
🇨ðŸ‡Zürich, Switzerland
Baskent University Hospital
🇹🇷Adana, Turkey
NL-Eindhoven-MAXIMAMC
🇳🇱Eindhoven, Netherlands
NL-Emmen-SCHEPER
🇳🇱Emmen, Netherlands
Orebro University Hospital
🇸🇪Örebro, Sweden
AU-Brisbane-PAH
🇦🇺Brisbane, Australia
Landeskrankenhaus Salzburg
🇦🇹Salzburg, Austria
AU-Melbourne-ALFRED
🇦🇺Melbourne, Australia
AU-Sydney-CONCORD
🇦🇺Sydney, Australia
BE-Antwerpen Edegem-UZA
🇧🇪Antwerpen, Belgium
DK-Herlev-HERLEV
🇩🇰Herlev, Denmark
CZ-Brno-UHBRNO
🇨🇿Brno, Czechia
Prince of Wales Hospital
🇦🇺Sydney, Australia
BE-Antwerpen-ZNASTUIVENBERG
🇧🇪Antwerpen, Belgium
BE-Mons-AMBROISE
🇧🇪Mons, Belgium
AZ Turnhout
🇧🇪Turnhout, Belgium
DK-Odense-OUH
🇩🇰Odense, Denmark
University Hospital Kralovske Vinohrady
🇨🇿Prague, Czechia
University Hospital Plzen
🇨🇿Plzen, Czechia
DK-Roskilde-ROSKILDE
🇩🇰Roskilde, Denmark
DK-Copenhagen-RIGSHOSPITALET
🇩🇰Copenhagen, Denmark
CZ-Ostrava-Poruba-FNO
🇨🇿Ostrava, Czechia
RHMS
🇧🇪Saint-Ghislain, Belgium
DK-Aalborg-AALBORGUH
🇩🇰Aalborg, Denmark
DK-Aarhus N-AUH
🇩🇰Aarhus, Denmark
Kralove-University Hospital Hradec Kralove
🇨🇿Hradec, Czechia
CZ-Olomouc-FNOL
🇨🇿Olomouc, Czechia
Osp S Maria delle Croci_Ema
🇮🇹Ravenna, Italy
St. Maria_Oncoematologia
🇮🇹Terni, Italy
Inst Regina elena-SC Ema IFO
🇮🇹Roma, Italy
NL-Venlo-VIECURI
🇳🇱Venlo, Netherlands
NL-Winterswijk-SKBWINTERSWIJK
🇳🇱Winterswijk, Netherlands
NO-Lørenskog-AKERSHUS
🇳🇴Lørenskog, Norway
Hallands Hospital Halmstad
🇸🇪Halmstad, Sweden
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Osp. san Camillo Forlanini
🇮🇹Roma, Italy
AOU Ospedali Riuniti
🇮🇹Trieste, Italy
NL-Arnhem-RIJNSTATE
🇳🇱Arnhem, Netherlands
Harstad University Hospital
🇳🇴Harstad, Norway
NL-Utrecht-UMCUTRECHT
🇳🇱Utrecht, Netherlands
Sørlandet Hospital
🇳🇴Kristiansand, Norway
AU-Sydney-NEPEAN
🇦🇺Sydney, Australia
AU-Canberra-CANBERRAHOSPITAL
🇦🇺Canberra, Australia
St George Hospital
🇦🇺Sydney, Australia
Krankenhaus d.Elisabethinen
🇦🇹Linz, Austria
FI-Turku-TYKS
🇫🇮Turku, Finland
Fondazione Maugeri
🇮🇹Pavia, Italy
Azienda Ospedaliera S. Maria della Misericordia
🇮🇹Perugia, Italy
AO Ospedali Riunti Marche Nord
🇮🇹Pesaro, Italy
Presidio Osp dello Spirito Santo
🇮🇹Pescara, Italy
A.O. Bianchi Melacrino Morelli_Ops Riunti
🇮🇹Reggio Calabria, Italy
Azienda Ospedaliera S. Maria Nuova
🇮🇹Reggio Emilia, Italy
Ospedale Oncologica Regionale
🇮🇹Rionero In Vulture, Italy
Ospedale San Giovanni Addolorata
🇮🇹Roma, Italy
Ospedale S Eugenio_Ema
🇮🇹Roma, Italy
Universita La Sapienza_Ospedale Umberto I
🇮🇹Roma, Italy
UC Biomedico_Divisione di Ematologia
🇮🇹Roma, Italy
AOU Senese Policlinico S. Maria alle Scotte
🇮🇹Siena, Italy
PO SS Ann e S.G. Moscati-Ema
🇮🇹Taranto, Italy
San Giovanni Battista Le Molinette-Ema 1
🇮🇹Torino, Italy
AO Cardinale G. Panico
🇮🇹Tricase, Italy
San Giovanni Battista Le Molinette-Ema 2
🇮🇹Torino, Italy
LU-Luxembourg-CHL
🇱🇺Luxembourg, Luxembourg
AOU S.Maria della Misericordia
🇮🇹Udine, Italy
NL-Alkmaar-NWZ
🇳🇱Alkmaar, Netherlands
NL-Almere-FLEVOZIEKENHUIS
🇳🇱Almere, Netherlands
NL-Amstelveen-AMSTELLAND
🇳🇱Amstelveen, Netherlands
NL-Amersfoort-MEANDERMC
🇳🇱Amersfoort, Netherlands
NL-Amsterdam-AVL
🇳🇱Amsterdam, Netherlands
NL-Amsterdam-AMC
🇳🇱Amsterdam, Netherlands
NL-Amsterdam-VUMC
🇳🇱Amsterdam, Netherlands
NL-Apeldoorn-GELREAPELDOORN
🇳🇱Apeldoorn, Netherlands
NL-Amsterdam-OLVG
🇳🇱Amsterdam, Netherlands
NL-Assen-WZA
🇳🇱Assen, Netherlands
NL-Breda-AMPHIA
🇳🇱Breda, Netherlands
NL-Beverwijk-RKZ
🇳🇱Beverwijk, Netherlands
NL-Capelle a/d IJssel-YSL
🇳🇱Capelle Aan Den IJssel, Netherlands
NL-Delft-RDGG
🇳🇱Delft, Netherlands
NL-Den Bosch-JBZ
🇳🇱Den Bosch, Netherlands
NL-Deventer-DZ
🇳🇱Deventer, Netherlands
NL-Dirksland-VANWEELBETHESDA
🇳🇱Dirksland, Netherlands
Nij Smellinghe
🇳🇱Drachten, Netherlands
NL-Eindhoven-CATHARINA
🇳🇱Eindhoven, Netherlands
NL-Ede-ZGV
🇳🇱Ede, Netherlands
NL-Enschede-MST
🇳🇱Enschede, Netherlands
NL-Gouda-GROENEHART
🇳🇱Gouda, Netherlands
NL-Goes-ADRZ
🇳🇱Goes, Netherlands
NL-Groningen-UMCG
🇳🇱Groningen, Netherlands
NL-Helmond-ELKERLIEK
🇳🇱Helmond, Netherlands
NL-Leeuwarden-MCL
🇳🇱Leeuwarden, Netherlands
NL-Hoofddorp-SPAARNEGASTHUIS
🇳🇱Hoofddorp, Netherlands
NL-Nieuwegein-ANTONIUS
🇳🇱Nieuwegein, Netherlands
NL-Roermond-LZR
🇳🇱Roermond, Netherlands
NL-Nijmegen-CWZ
🇳🇱Nijmegen, Netherlands
NL-Roosendaal-BRAVIS
🇳🇱Roosendaal, Netherlands
NL-Rotterdam-MAASSTADZIEKENHUIS
🇳🇱Rotterdam, Netherlands
NL-Rotterdam-SFG
🇳🇱Rotterdam, Netherlands
NL-Sittard-Geleen-ZUYDERLAND
🇳🇱Sittard, Netherlands
NL-Spijkenisse-SPIJKENISSEMC
🇳🇱Spijkenisse, Netherlands
NL-Utrecht-DIAKONESSENUTRECHT
🇳🇱Utrecht, Netherlands
NL-Zwolle-ISALA
🇳🇱Zwolle, Netherlands
Haukeland University Hospital
🇳🇴Bergen, Norway
Forde Central Hosiptal
🇳🇴Førde, Norway
Levanger Hospital
🇳🇴Levanger, Norway
NO-Oslo-OSLOUH
🇳🇴Oslo, Norway
Baerum hospital
🇳🇴Sandvika, Norway
NO-Tromsø-NORTHNOORWEGEN
🇳🇴Tromsø, Norway
NO-Stavanger-HELSESTAVANGER
🇳🇴Stavanger, Norway
Helse Sunnmore
🇳🇴Ålesund, Norway
Sahlgrenska University Hospital
🇸🇪Göteborg, Sweden
SE-Boras-SASBORAS
🇸🇪Borås, Sweden
Francisco Gentil
🇵🇹Lisboa, Portugal
Eskilstuna Malar Hospital
🇸🇪Eskilstuna, Sweden
Falun Hospital
🇸🇪Falun, Sweden
Ryhov Hospital
🇸🇪Jönköping, Sweden
Helsingborg General Hospital
🇸🇪Helsingborg, Sweden
Lidkoping Hospital
🇸🇪Lidkoping, Sweden
SE-Linköping-REGIONOSTERGOTLAND
🇸🇪Linköping, Sweden
SE-Luleå-SUNDERBY
🇸🇪Luleå, Sweden
SE-Lund-SUH
🇸🇪Lund, Sweden
Uddevall Hospital
🇸🇪Uddevalla, Sweden
SE-Stockholm-KAROLINSKAHUDDINGE
🇸🇪Stockholm, Sweden
Sundsvall Hospital
🇸🇪Sundsvall, Sweden
Umea University Hospital
🇸🇪Umeå, Sweden
SE-Uppsala-UPPSALAUH
🇸🇪Uppsala, Sweden
Centrallasareltet Vaxjo
🇸🇪Växjö, Sweden
CH-Aarau-KSA
🇨ðŸ‡Aarau, Switzerland
CH-Bellinzona-IOSI
🇨ðŸ‡Bellinzona, Switzerland
CH-Basel-USB
🇨ðŸ‡Basel, Switzerland
Kantonsspital Baselland
🇨ðŸ‡Liestal, Switzerland
KS Graubunden
🇨ðŸ‡Chur, Switzerland
CH-Geneve (14)-HCUGE
🇨ðŸ‡Geneve, Switzerland
CH-St. Gallen-KSSG
🇨ðŸ‡Saint Gallen, Switzerland
CH-Luzern-LUKS
🇨ðŸ‡Luzern, Switzerland
University Hospital Ankara
🇹🇷Ankara, Turkey
Istanbul University Hospital
🇹🇷Istanbul, Turkey
Ege University Hospital
🇹🇷İzmir, Turkey
Erciyes University Hospital
🇹🇷Kayseri, Turkey