Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma (HO95)
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma (Kahler's disease)
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- AU-Brisbane-PAH
- AU-Canberra-CANBERRAHOSPITAL
- AU-Melbourne-ALFRED
- AU-Sydney-CONCORD
- AU-Sydney-NEPEAN
- Prince of Wales Hospital
- St George Hospital
- Krankenhaus d.Elisabethinen
- Landeskrankenhaus Salzburg
- AT-Vienna-HANUSCH
- BE-Antwerpen Edegem-UZA
- BE-Antwerpen-ZNASTUIVENBERG
- BE-Haine-Saint-Paul-JOLIMONT
- CHU Tivoli
- BE-Liege-CHRCITADELLE
- BE-Mons-AMBROISE
- CHR Saint Joseph
- BE-Roeselare-AZDELTA
- RHMS
- CH Wapi
- AZ Turnhout
- CZ-Brno-UHBRNO
- Kralove-University Hospital Hradec Kralove
- CZ-Olomouc-FNOL
- CZ-Ostrava-Poruba-FNO
- University Hospital Plzen
- University Hospital Kralovske Vinohrady
- DK-Aalborg-AALBORGUH
- DK-Aarhus N-AUH
- DK-Copenhagen-RIGSHOSPITALET
- DK-Herlev-HERLEV
- DK-Odense-OUH
- DK-Roskilde-ROSKILDE
- FI-Turku-TYKS
- GR-Athens-ALEXANDRA
- St. Istvan and St. Laszlo Korhaz Hospital
- Szeged University Hospital
- SS Antonio e Biogio
- AOU Umberto I-Clinica di Ematologica
- Ospedale C. e G. Mazzoni-Ematologia
- A.O.R.N. San G. Moscati
- Policlinico di Bari
- Oaspedali Riuniti_Div di Ematologia
- Instituto di Ematologia e Oncologia Medica
- Ospedale Generale Regionale_Div di Ema e Centro
- Spedali Civili_U.O.Ematologia
- Pres Osp Di Summa
- Presidio Osp R. Binaghi
- Inst per la Ricerca e la Cura del Cancro Di
- Ospedale Ferrarotto-Ema
- Presidio ospedaliero dell'annunziata
- OspedaleCivico S Croce e carle
- Ospedali Riuniti di Foggia
- Azienda Ospedaliera San Antonio Abate
- Azienda Ospedaliera Universitaria S. Martino_Clinica Ematologica
- Azienda Ospedaliera Universitaria S. Martino_Ematologia 1
- Azienda Ospedaliera Universitaria S. Martino_Ematologia 2
- Università La Sapienza Polo Pontino
- Ospedale A. Manzoni
- ASUR Regione Marche
- IRST
- Azienda Ospedaliera Papardo
- Policlinico Gaetano Martino
- Osp Dell Angelo
- Istituto Nazionale dei Tumori-Ema
- Ospedale Niguarda Cà Grande
- Policlinico- servizio di Ematologia
- Ospedale Cardarelli-ematologia e Trapianto di Midollo Osseo
- Ospedale Cardarelli-Sezione di Ematologia TERE
- Universita Federico II-Ema
- Università Amedeo Avogrado-Ospedale Maggiore
- Ospedale San Francesco
- Osp San Luigi Gonzaga-Pat med
- Ospedaliera di Pavona_Ematologia e
- Giaccone di Palermo
- Fondazione Maugeri
- Policlinico San Matteo
- Azienda Ospedaliera S. Maria della Misericordia
- AO Ospedali Riunti Marche Nord
- Presidio Osp dello Spirito Santo
- Osp S Maria delle Croci_Ema
- A.O. Bianchi Melacrino Morelli_Ops Riunti
- Azienda Ospedaliera S. Maria Nuova
- Ospedale Infermi
- Ospedale Oncologica Regionale
- Azienda Osp S. Andrea
- Inst Regina elena-SC Ema IFO
- Osp. san Camillo Forlanini
- Ospedale S Eugenio_Ema
- Ospedale San Giovanni Addolorata
- UC Biomedico_Divisione di Ematologia
- Universita La Sapienza_Ospedale Umberto I
- Istituto Clinico Humanitas
- AOU Senese Policlinico S. Maria alle Scotte
- PO SS Ann e S.G. Moscati-Ema
- St. Maria_Oncoematologia
- San Giovanni Battista Le Molinette-Ema 1
- San Giovanni Battista Le Molinette-Ema 2
- AO Cardinale G. Panico
- AOU Ospedali Riuniti
- AOU S.Maria della Misericordia
- LU-Luxembourg-CHL
- NL-Alkmaar-NWZ
- NL-Almere-FLEVOZIEKENHUIS
- NL-Amersfoort-MEANDERMC
- NL-Amstelveen-AMSTELLAND
- NL-Amsterdam-AMC
- NL-Amsterdam-AVL
- NL-Amsterdam-OLVG
- NL-Amsterdam-VUMC
- NL-Apeldoorn-GELREAPELDOORN
- NL-Arnhem-RIJNSTATE
- NL-Assen-WZA
- NL-Beverwijk-RKZ
- NL-Breda-AMPHIA
- NL-Capelle a/d IJssel-YSL
- NL-Delft-RDGG
- NL-Den Bosch-JBZ
- NL-Den Haag-HAGA
- NL-Deventer-DZ
- NL-Dirksland-VANWEELBETHESDA
- NL-Doetinchem-SLINGELAND
- NL-Dordrecht-ASZ
- Nij Smellinghe
- NL-Ede-ZGV
- NL-Eindhoven-CATHARINA
- NL-Eindhoven-MAXIMAMC
- NL-Emmen-SCHEPER
- NL-Enschede-MST
- NL-Geldrop-STANNA
- NL-Goes-ADRZ
- NL-Gorinchem-BEATRIX
- NL-Gouda-GROENEHART
- NL-Groningen-UMCG
- NL-Heerlen-ATRIUMMC
- NL-Helmond-ELKERLIEK
- NL-Hilversum-TERGOOI
- NL-Hoofddorp-SPAARNEGASTHUIS
- NL-Hoorn-DIJKLANDERHOORN
- NL-Leeuwarden-MCL
- NL-Leiden-LUMC
- NL-Maastricht-MUMC
- NL-Nieuwegein-ANTONIUS
- NL-Nijmegen-CWZ
- NL-Nijmegen-RADBOUDUMC
- NL-Roermond-LZR
- NL-Roosendaal-BRAVIS
- NL-Rotterdam-EMCDANIEL
- NL-Rotterdam-ERASMUSMC
- NL-Rotterdam-IKAZIA
- NL-Rotterdam-MAASSTADZIEKENHUIS
- NL-Rotterdam-SFG
- NL-Sittard-Geleen-ZUYDERLAND
- NL-Spijkenisse-SPIJKENISSEMC
- NL-Terneuzen-ZORGSAAM
- NL-Tilburg-ETZ
- NL-Utrecht-DIAKONESSENUTRECHT
- NL-Utrecht-UMCUTRECHT
- NL-Venlo-VIECURI
- NL-Winterswijk-SKBWINTERSWIJK
- NL-Zwolle-ISALA
- Haukeland University Hospital
- Forde Central Hosiptal
- Harstad University Hospital
- Sørlandet Hospital
- Levanger Hospital
- NO-Lørenskog-AKERSHUS
- NO-Oslo-OSLOUH
- Baerum hospital
- NO-Stavanger-HELSESTAVANGER
- NO-Tromsø-NORTHNOORWEGEN
- NO-Trondheim-STOLAV
- Helse Sunnmore
- Francisco Gentil
- SE-Boras-SASBORAS
- Eskilstuna Malar Hospital
- Falun Hospital
- Sahlgrenska University Hospital
- Hallands Hospital Halmstad
- Helsingborg General Hospital
- Ryhov Hospital
- Lidkoping Hospital
- SE-Linköping-REGIONOSTERGOTLAND
- SE-Luleå-SUNDERBY
- SE-Lund-SUH
- SE-Stockholm-KAROLINSKAHUDDINGE
- Sundsvall Hospital
- Uddevall Hospital
- Umea University Hospital
- SE-Uppsala-UPPSALAUH
- Centrallasareltet Vaxjo
- Orebro University Hospital
- CH-Aarau-KSA
- CH-Basel-USB
- CH-Bellinzona-IOSI
- CH-Bern-INSEL
- KS Graubunden
- CH-Geneve (14)-HCUGE
- Kantonsspital Baselland
- CH-Luzern-LUKS
- CH-St. Gallen-KSSG
- CH-Zürich-USZ
- Baskent University Hospital
- Gazi University Hospital
- University Hospital Ankara
- Istanbul University Hospital
- Ege University Hospital
- Erciyes University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
No Intervention
Experimental
R1: 4 cycles Bortezomib, Melphalan, Prednisone (VMP)
R1: 1 (2) cycle(s) HDM
R2: none
R2: 2 cycles of VRD
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.
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.
No consolidation, patients will continue to Lenalidomide maintenance.
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.