Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma

Multiple Myeloma Clinical Trial

— HO95  

Official title:

A Randomized Phase III Study to Compare Bortezomib, Melphalan, Prednisone (VMP) With High Dose Melphalan Followed by Bortezomib, Lenalidomide, Dexamethasone (VRD) Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01208766
• Other study ID #: HOVON 95 MM
• Secondary ID: 2009-017903-28EM
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 2011
• Est. completion date: April 2024

Study information

• Verified date: August 2023
• Source: Stichting Hemato-Oncologie voor Volwassenen Nederland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1503
• Est. completion date: April 2024
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib, Melphalan, Prednisone (VMP)
Bortezomib _ 1.3 mg/m2 _ i.v. rapid infusion _ days 1,4,8,11,22,25,29,32 Melphalan _ 9 mg/m² _ p.o. _ days 1-4 Prednisone _ 60 mg/m² _ p.o. _ days 1-4
• 1 or 2 cycle(s) HDM (High Dose Melphalan)
- Melphalan _ 100 mg/m² _ i.v. rapid infusion _ -3, -2* *Patients with renal insufficiency 100 mg/m2 only at day -3 If a patient is randomized to receive 2 x HDM a second course of High Dose Melphalan may be administered between 2 and 3 months after the first course when the patient achieved at least PR.
• 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)
Bortezomib _ 1.3 mg/m2 _ i.v. rapid infusion _ days 1,4,8,11 Lenalidomide _ 25 mg _ p.o. _ days 1-21 Dexamethasone _ 20 mg _ p.o. _ days 1,2,4,5,8,9,11,12

Locations

Country	Name	City	State
Australia	AU-Brisbane-PAH	Brisbane
Australia	AU-Canberra-CANBERRAHOSPITAL	Canberra
Australia	AU-Melbourne-ALFRED	Melbourne
Australia	AU-Sydney-CONCORD	Sydney
Australia	AU-Sydney-NEPEAN	Sydney
Australia	Prince of Wales Hospital	Sydney
Australia	St George Hospital	Sydney
Austria	Krankenhaus d.Elisabethinen	Linz
Austria	Landeskrankenhaus Salzburg	Salzburg
Austria	AT-Vienna-HANUSCH	Vienna
Belgium	BE-Antwerpen Edegem-UZA	Antwerpen
Belgium	BE-Antwerpen-ZNASTUIVENBERG	Antwerpen
Belgium	BE-Haine-Saint-Paul-JOLIMONT	Haine-Saint-Paul
Belgium	CHU Tivoli	La Louvière
Belgium	BE-Liege-CHRCITADELLE	Liège
Belgium	BE-Mons-AMBROISE	Mons
Belgium	CHR Saint Joseph	Mons
Belgium	BE-Roeselare-AZDELTA	Roeselare
Belgium	RHMS	Saint-Ghislain
Belgium	CH Wapi	Tournai
Belgium	AZ Turnhout	Turnhout
Czechia	CZ-Brno-UHBRNO	Brno
Czechia	Kralove-University Hospital Hradec Kralove	Hradec
Czechia	CZ-Olomouc-FNOL	Olomouc
Czechia	CZ-Ostrava-Poruba-FNO	Ostrava
Czechia	University Hospital Plzen	Plzen
Czechia	University Hospital Kralovske Vinohrady	Prague
Denmark	DK-Aalborg-AALBORGUH	Aalborg
Denmark	DK-Aarhus N-AUH	Aarhus
Denmark	DK-Copenhagen-RIGSHOSPITALET	Copenhagen
Denmark	DK-Herlev-HERLEV	Herlev
Denmark	DK-Odense-OUH	Odense
Denmark	DK-Roskilde-ROSKILDE	Roskilde
Finland	FI-Turku-TYKS	Turku
Greece	GR-Athens-ALEXANDRA	Athens
Hungary	St. Istvan and St. Laszlo Korhaz Hospital	Budapest
Hungary	Szeged University Hospital	Szeged
Italy	SS Antonio e Biogio	Alessandria
Italy	AOU Umberto I-Clinica di Ematologica	Ancona
Italy	Ospedale C. e G. Mazzoni-Ematologia	Ascoli Piceno
Italy	A.O.R.N. San G. Moscati	Avellino
Italy	Policlinico di Bari	Bari
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	Presidio Osp R. Binaghi	Cagliari
Italy	Inst per la Ricerca e la Cura del Cancro Di	Candiolo
Italy	Ospedale Ferrarotto-Ema	Catania
Italy	Presidio ospedaliero dell'annunziata	Cosenza
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	Azienda Ospedaliera Universitaria S. Martino_Ematologia 2	Genova
Italy	Università La Sapienza Polo Pontino	Latina
Italy	Ospedale A. Manzoni	Lecco
Italy	ASUR Regione Marche	Marche
Italy	IRST	Meldola
Italy	Azienda Ospedaliera Papardo	Messina
Italy	Policlinico Gaetano Martino	Messina
Italy	Osp Dell Angelo	Mestre
Italy	Istituto Nazionale dei Tumori-Ema	Milano
Italy	Ospedale Niguarda Cà Grande	Milano
Italy	Policlinico- servizio di Ematologia	Modena
Italy	Ospedale Cardarelli-ematologia e Trapianto di Midollo Osseo	Napoli
Italy	Ospedale Cardarelli-Sezione di Ematologia TERE	Napoli
Italy	Universita Federico II-Ema	Napoli
Italy	Università Amedeo Avogrado-Ospedale Maggiore	Novara
Italy	Ospedale San Francesco	Nuoro
Italy	Osp San Luigi Gonzaga-Pat med	Orbassano
Italy	Ospedaliera di Pavona_Ematologia e	Padova
Italy	Giaccone di Palermo	Palermo
Italy	Fondazione Maugeri	Pavia
Italy	Policlinico San Matteo	Pavia
Italy	Azienda Ospedaliera S. Maria della Misericordia	Perugia
Italy	AO Ospedali Riunti Marche Nord	Pesaro
Italy	Presidio Osp dello Spirito Santo	Pescara
Italy	Osp S Maria delle Croci_Ema	Ravenna
Italy	A.O. Bianchi Melacrino Morelli_Ops Riunti	Reggio Calabria
Italy	Azienda Ospedaliera S. Maria Nuova	Reggio Emilia
Italy	Ospedale Infermi	Rimini
Italy	Ospedale Oncologica Regionale	Rionero In Vulture
Italy	Azienda Osp S. Andrea	Roma
Italy	Inst Regina elena-SC Ema IFO	Roma
Italy	Osp. san Camillo Forlanini	Roma
Italy	Ospedale S Eugenio_Ema	Roma
Italy	Ospedale San Giovanni Addolorata	Roma
Italy	UC Biomedico_Divisione di Ematologia	Roma
Italy	Universita La Sapienza_Ospedale Umberto I	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Italy	AOU Senese Policlinico S. Maria alle Scotte	Siena
Italy	PO SS Ann e S.G. Moscati-Ema	Taranto
Italy	St. Maria_Oncoematologia	Terni
Italy	San Giovanni Battista Le Molinette-Ema 1	Torino
Italy	San Giovanni Battista Le Molinette-Ema 2	Torino
Italy	AO Cardinale G. Panico	Tricase
Italy	AOU Ospedali Riuniti	Trieste
Italy	AOU S.Maria della Misericordia	Udine
Luxembourg	LU-Luxembourg-CHL	Luxembourg
Netherlands	NL-Alkmaar-NWZ	Alkmaar
Netherlands	NL-Almere-FLEVOZIEKENHUIS	Almere
Netherlands	NL-Amersfoort-MEANDERMC	Amersfoort
Netherlands	NL-Amstelveen-AMSTELLAND	Amstelveen
Netherlands	NL-Amsterdam-AMC	Amsterdam
Netherlands	NL-Amsterdam-AVL	Amsterdam
Netherlands	NL-Amsterdam-OLVG	Amsterdam
Netherlands	NL-Amsterdam-VUMC	Amsterdam
Netherlands	NL-Apeldoorn-GELREAPELDOORN	Apeldoorn
Netherlands	NL-Arnhem-RIJNSTATE	Arnhem
Netherlands	NL-Assen-WZA	Assen
Netherlands	NL-Beverwijk-RKZ	Beverwijk
Netherlands	NL-Breda-AMPHIA	Breda
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-Den Haag-HAGA	Den Haag
Netherlands	NL-Deventer-DZ	Deventer
Netherlands	NL-Dirksland-VANWEELBETHESDA	Dirksland
Netherlands	NL-Doetinchem-SLINGELAND	Doetinchem
Netherlands	NL-Dordrecht-ASZ	Dordrecht
Netherlands	Nij Smellinghe	Drachten
Netherlands	NL-Ede-ZGV	Ede
Netherlands	NL-Eindhoven-CATHARINA	Eindhoven
Netherlands	NL-Eindhoven-MAXIMAMC	Eindhoven
Netherlands	NL-Emmen-SCHEPER	Emmen
Netherlands	NL-Enschede-MST	Enschede
Netherlands	NL-Geldrop-STANNA	Geldrop
Netherlands	NL-Goes-ADRZ	Goes
Netherlands	NL-Gorinchem-BEATRIX	Gorinchem
Netherlands	NL-Gouda-GROENEHART	Gouda
Netherlands	NL-Groningen-UMCG	Groningen
Netherlands	NL-Heerlen-ATRIUMMC	Heerlen
Netherlands	NL-Helmond-ELKERLIEK	Helmond
Netherlands	NL-Hilversum-TERGOOI	Hilversum
Netherlands	NL-Hoofddorp-SPAARNEGASTHUIS	Hoofddorp
Netherlands	NL-Hoorn-DIJKLANDERHOORN	Hoorn
Netherlands	NL-Leeuwarden-MCL	Leeuwarden
Netherlands	NL-Leiden-LUMC	Leiden
Netherlands	NL-Maastricht-MUMC	Maastricht
Netherlands	NL-Nieuwegein-ANTONIUS	Nieuwegein
Netherlands	NL-Nijmegen-CWZ	Nijmegen
Netherlands	NL-Nijmegen-RADBOUDUMC	Nijmegen
Netherlands	NL-Roermond-LZR	Roermond
Netherlands	NL-Roosendaal-BRAVIS	Roosendaal
Netherlands	NL-Rotterdam-EMCDANIEL	Rotterdam
Netherlands	NL-Rotterdam-ERASMUSMC	Rotterdam
Netherlands	NL-Rotterdam-IKAZIA	Rotterdam
Netherlands	NL-Rotterdam-MAASSTADZIEKENHUIS	Rotterdam
Netherlands	NL-Rotterdam-SFG	Rotterdam
Netherlands	NL-Sittard-Geleen-ZUYDERLAND	Sittard
Netherlands	NL-Spijkenisse-SPIJKENISSEMC	Spijkenisse
Netherlands	NL-Terneuzen-ZORGSAAM	Terneuzen
Netherlands	NL-Tilburg-ETZ	Tilburg
Netherlands	NL-Utrecht-DIAKONESSENUTRECHT	Utrecht
Netherlands	NL-Utrecht-UMCUTRECHT	Utrecht
Netherlands	NL-Venlo-VIECURI	Venlo
Netherlands	NL-Winterswijk-SKBWINTERSWIJK	Winterswijk
Netherlands	NL-Zwolle-ISALA	Zwolle
Norway	Helse Sunnmore	Ålesund
Norway	Haukeland University Hospital	Bergen
Norway	Forde Central Hosiptal	Førde
Norway	Harstad University Hospital	Harstad
Norway	Sørlandet Hospital	Kristiansand
Norway	Levanger Hospital	Levanger
Norway	NO-Lørenskog-AKERSHUS	Lørenskog
Norway	NO-Oslo-OSLOUH	Oslo
Norway	Baerum hospital	Sandvika
Norway	NO-Stavanger-HELSESTAVANGER	Stavanger
Norway	NO-Tromsø-NORTHNOORWEGEN	Tromsø
Norway	NO-Trondheim-STOLAV	Trondheim
Portugal	Francisco Gentil	Lisboa
Sweden	SE-Boras-SASBORAS	Borås
Sweden	Eskilstuna Malar Hospital	Eskilstuna
Sweden	Falun Hospital	Falun
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Hallands Hospital Halmstad	Halmstad
Sweden	Helsingborg General Hospital	Helsingborg
Sweden	Ryhov Hospital	Jönköping
Sweden	Lidkoping Hospital	Lidkoping
Sweden	SE-Linköping-REGIONOSTERGOTLAND	Linköping
Sweden	SE-Luleå-SUNDERBY	Luleå
Sweden	SE-Lund-SUH	Lund
Sweden	Orebro University Hospital	Örebro
Sweden	SE-Stockholm-KAROLINSKAHUDDINGE	Stockholm
Sweden	Sundsvall Hospital	Sundsvall
Sweden	Uddevall Hospital	Uddevalla
Sweden	Umea University Hospital	Umeå
Sweden	SE-Uppsala-UPPSALAUH	Uppsala
Sweden	Centrallasareltet Vaxjo	Växjö
Switzerland	CH-Aarau-KSA	Aarau
Switzerland	CH-Basel-USB	Basel
Switzerland	CH-Bellinzona-IOSI	Bellinzona
Switzerland	CH-Bern-INSEL	Bern
Switzerland	KS Graubunden	Chur
Switzerland	CH-Geneve (14)-HCUGE	Geneve
Switzerland	Kantonsspital Baselland	Liestal
Switzerland	CH-Luzern-LUKS	Luzern
Switzerland	CH-St. Gallen-KSSG	Saint Gallen
Switzerland	CH-Zürich-USZ	Zürich
Turkey	Baskent University Hospital	Adana
Turkey	Gazi University Hospital	Ankara
Turkey	University Hospital Ankara	Ankara
Turkey	Istanbul University Hospital	Istanbul
Turkey	Ege University Hospital	Izmir
Turkey	Erciyes University Hospital	Kayseri

Sponsors (6)

Lead Sponsor	Collaborator
Stichting Hemato-Oncologie voor Volwassenen Nederland	Central European Myeloma Study Group, DSMM (Deutsche Studiengruppe Multiples Myelom), European Myeloma Network, Gruppo Italiano Malattie EMatologiche dell'Adulto, NMSG (Nordic Myeloma Study Group)

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Czechia,  Denmark,  Finland,  Greece,  Hungary,  Italy,  Luxembourg,  Netherlands,  Norway,  Portugal,  Sweden,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 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)
Primary	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 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)
Primary	For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes 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)
Secondary	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.	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)
Secondary	Toxicity	Toxicity	End of trial (last patient last visit)
Secondary	Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment.	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)

External Links

•   Hovon website