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

NCT ID: NCT01208766

Last Updated: 2026-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1503 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-31

Study Completion Date

2025-01-31

Brief Summary

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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

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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R1: 4 cycles 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.

Group Type ACTIVE_COMPARATOR

Bortezomib, Melphalan, Prednisone (VMP)

Intervention Type DRUG

* 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

R1: 1 (2) cycle(s) HDM

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.

Group Type EXPERIMENTAL

1 or 2 cycle(s) HDM (High Dose Melphalan)

Intervention Type DRUG

\- 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.

R2: none

No consolidation, patients will continue to Lenalidomide maintenance.

Group Type NO_INTERVENTION

No interventions assigned to this group

R2: 2 cycles of 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.

Group Type EXPERIMENTAL

2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)

Intervention Type DRUG

* 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

Interventions

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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

Intervention Type DRUG

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.

Intervention Type DRUG

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European Myeloma Network B.V.

NETWORK

Sponsor Role collaborator

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role collaborator

DSMM (Deutsche Studiengruppe Multiples Myelom)

UNKNOWN

Sponsor Role collaborator

NMSG (Nordic Myeloma Study Group)

UNKNOWN

Sponsor Role collaborator

Central European Myeloma Study Group

OTHER

Sponsor Role collaborator

Stichting Hemato-Oncologie voor Volwassenen Nederland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pieter Sonneveld, Prof.

Role: PRINCIPAL_INVESTIGATOR

Stichting Hemato-Oncologie voor Volwassenen Nederland

Locations

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AU-Brisbane-PAH

Brisbane, , Australia

Site Status

AU-Canberra-CANBERRAHOSPITAL

Canberra, , Australia

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AU-Melbourne-ALFRED

Melbourne, , Australia

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AU-Sydney-CONCORD

Sydney, , Australia

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AU-Sydney-NEPEAN

Sydney, , Australia

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Prince of Wales Hospital

Sydney, , Australia

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St George Hospital

Sydney, , Australia

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Krankenhaus d.Elisabethinen

Linz, , Austria

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Landeskrankenhaus Salzburg

Salzburg, , Austria

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AT-Vienna-HANUSCH

Vienna, , Austria

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BE-Antwerpen Edegem-UZA

Antwerp, , Belgium

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BE-Antwerpen-ZNASTUIVENBERG

Antwerp, , Belgium

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BE-Haine-Saint-Paul-JOLIMONT

Haine-Saint-Paul, , Belgium

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CHU Tivoli

La Louvière, , Belgium

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BE-Liege-CHRCITADELLE

Liège, , Belgium

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BE-Mons-AMBROISE

Mons, , Belgium

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CHR Saint Joseph

Mons, , Belgium

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BE-Roeselare-AZDELTA

Roeselare, , Belgium

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RHMS

Saint-Ghislain, , Belgium

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CH Wapi

Tournai, , Belgium

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AZ Turnhout

Turnhout, , Belgium

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CZ-Brno-UHBRNO

Brno, , Czechia

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Kralove-University Hospital Hradec Kralove

Hradec, , Czechia

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CZ-Olomouc-FNOL

Olomouc, , Czechia

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CZ-Ostrava-Poruba-FNO

Ostrava, , Czechia

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University Hospital Plzen

Pilsen, , Czechia

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University Hospital Kralovske Vinohrady

Prague, , Czechia

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DK-Aalborg-AALBORGUH

Aalborg, , Denmark

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DK-Aarhus N-AUH

Aarhus, , Denmark

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DK-Copenhagen-RIGSHOSPITALET

Copenhagen, , Denmark

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DK-Herlev-HERLEV

Herlev, , Denmark

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DK-Odense-OUH

Odense, , Denmark

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DK-Roskilde-ROSKILDE

Roskilde, , Denmark

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FI-Turku-TYKS

Turku, , Finland

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GR-Athens-ALEXANDRA

Athens, , Greece

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St. Istvan and St. Laszlo Korhaz Hospital

Budapest, , Hungary

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Szeged University Hospital

Szeged, , Hungary

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SS Antonio e Biogio

Alessandria, , Italy

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AOU Umberto I-Clinica di Ematologica

Ancona, , Italy

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Ospedale C. e G. Mazzoni-Ematologia

Ascoli Piceno, , Italy

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A.O.R.N. San G. Moscati

Avellino, , Italy

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Policlinico di Bari

Bari, , Italy

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Oaspedali Riuniti_Div di Ematologia

Bergamo, , Italy

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Instituto di Ematologia e Oncologia Medica

Bologna, , Italy

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Ospedale Generale Regionale_Div di Ema e Centro

Bolzano, , Italy

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Spedali Civili_U.O.Ematologia

Brescia, , Italy

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Pres Osp Di Summa

Brindisi, , Italy

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Presidio Osp R. Binaghi

Cagliari, , Italy

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Inst per la Ricerca e la Cura del Cancro Di

Candiolo, , Italy

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Ospedale Ferrarotto-Ema

Catania, , Italy

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Presidio ospedaliero dell'annunziata

Cosenza, , Italy

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OspedaleCivico S Croce e carle

Cuneo, , Italy

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Ospedali Riuniti di Foggia

Foggia, , Italy

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Azienda Ospedaliera San Antonio Abate

Gallarate, , Italy

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Azienda Ospedaliera Universitaria S. Martino_Clinica Ematologica

Genova, , Italy

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Azienda Ospedaliera Universitaria S. Martino_Ematologia 1

Genova, , Italy

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Azienda Ospedaliera Universitaria S. Martino_Ematologia 2

Genova, , Italy

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Università La Sapienza Polo Pontino

Latina, , Italy

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Ospedale A. Manzoni

Lecco, , Italy

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ASUR Regione Marche

Marche, , Italy

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IRST

Meldola, , Italy

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Azienda Ospedaliera Papardo

Messina, , Italy

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Policlinico Gaetano Martino

Messina, , Italy

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Osp Dell Angelo

Mestre, , Italy

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Istituto Nazionale dei Tumori-Ema

Milan, , Italy

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Ospedale Niguarda Cà Grande

Milan, , Italy

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Policlinico- servizio di Ematologia

Modena, , Italy

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Ospedale Cardarelli-ematologia e Trapianto di Midollo Osseo

Napoli, , Italy

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Ospedale Cardarelli-Sezione di Ematologia TERE

Napoli, , Italy

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Universita Federico II-Ema

Napoli, , Italy

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Università Amedeo Avogrado-Ospedale Maggiore

Novara, , Italy

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Ospedale San Francesco

Nuoro, , Italy

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Osp San Luigi Gonzaga-Pat med

Orbassano, , Italy

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Ospedaliera di Pavona_Ematologia e

Padua, , Italy

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Giaccone di Palermo

Palermo, , Italy

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Fondazione Maugeri

Pavia, , Italy

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Policlinico San Matteo

Pavia, , Italy

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Azienda Ospedaliera S. Maria della Misericordia

Perugia, , Italy

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AO Ospedali Riunti Marche Nord

Pesaro, , Italy

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Presidio Osp dello Spirito Santo

Pescara, , Italy

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Osp S Maria delle Croci_Ema

Ravenna, , Italy

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A.O. Bianchi Melacrino Morelli_Ops Riunti

Reggio Calabria, , Italy

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Azienda Ospedaliera S. Maria Nuova

Reggio Emilia, , Italy

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Ospedale Infermi

Rimini, , Italy

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Ospedale Oncologica Regionale

Rionero in Vulture, , Italy

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Azienda Osp S. Andrea

Roma, , Italy

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Inst Regina elena-SC Ema IFO

Roma, , Italy

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Osp. san Camillo Forlanini

Roma, , Italy

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Ospedale S Eugenio_Ema

Roma, , Italy

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Ospedale San Giovanni Addolorata

Roma, , Italy

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UC Biomedico_Divisione di Ematologia

Roma, , Italy

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Universita La Sapienza_Ospedale Umberto I

Roma, , Italy

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Istituto Clinico Humanitas

Rozzano, , Italy

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AOU Senese Policlinico S. Maria alle Scotte

Siena, , Italy

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PO SS Ann e S.G. Moscati-Ema

Taranto, , Italy

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St. Maria_Oncoematologia

Terni, , Italy

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San Giovanni Battista Le Molinette-Ema 1

Torino, , Italy

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San Giovanni Battista Le Molinette-Ema 2

Torino, , Italy

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AO Cardinale G. Panico

Tricase, , Italy

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AOU Ospedali Riuniti

Trieste, , Italy

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AOU S.Maria della Misericordia

Udine, , Italy

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LU-Luxembourg-CHL

Luxembourg, , Luxembourg

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NL-Den Bosch-JBZ

's-Hertogenbosch, , Netherlands

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NL-Alkmaar-NWZ

Alkmaar, , Netherlands

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NL-Almere-FLEVOZIEKENHUIS

Almere Stad, , Netherlands

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NL-Amersfoort-MEANDERMC

Amersfoort, , Netherlands

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NL-Amstelveen-AMSTELLAND

Amstelveen, , Netherlands

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NL-Amsterdam-AMC

Amsterdam, , Netherlands

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NL-Amsterdam-AVL

Amsterdam, , Netherlands

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NL-Amsterdam-OLVG

Amsterdam, , Netherlands

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NL-Amsterdam-VUMC

Amsterdam, , Netherlands

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NL-Apeldoorn-GELREAPELDOORN

Apeldoorn, , Netherlands

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NL-Arnhem-RIJNSTATE

Arnhem, , Netherlands

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NL-Assen-WZA

Assen, , Netherlands

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NL-Beverwijk-RKZ

Beverwijk, , Netherlands

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NL-Breda-AMPHIA

Breda, , Netherlands

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NL-Capelle a/d IJssel-YSL

Capelle aan den IJssel, , Netherlands

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NL-Delft-RDGG

Delft, , Netherlands

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NL-Deventer-DZ

Deventer, , Netherlands

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NL-Dirksland-VANWEELBETHESDA

Dirksland, , Netherlands

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NL-Doetinchem-SLINGELAND

Doetinchem, , Netherlands

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NL-Dordrecht-ASZ

Dordrecht, , Netherlands

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Nij Smellinghe

Drachten, , Netherlands

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NL-Ede-ZGV

Ede, , Netherlands

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NL-Eindhoven-CATHARINA

Eindhoven, , Netherlands

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NL-Eindhoven-MAXIMAMC

Eindhoven, , Netherlands

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NL-Emmen-SCHEPER

Emmen, , Netherlands

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NL-Enschede-MST

Enschede, , Netherlands

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NL-Geldrop-STANNA

Geldrop, , Netherlands

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NL-Goes-ADRZ

Goes, , Netherlands

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NL-Gorinchem-BEATRIX

Gorinchem, , Netherlands

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NL-Gouda-GROENEHART

Gouda, , Netherlands

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NL-Groningen-UMCG

Groningen, , Netherlands

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NL-Heerlen-ATRIUMMC

Heerlen, , Netherlands

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NL-Helmond-ELKERLIEK

Helmond, , Netherlands

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NL-Hilversum-TERGOOI

Hilversum, , Netherlands

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NL-Hoofddorp-SPAARNEGASTHUIS

Hoofddorp, , Netherlands

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NL-Hoorn-DIJKLANDERHOORN

Hoorn, , Netherlands

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NL-Leeuwarden-MCL

Leeuwarden, , Netherlands

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NL-Leiden-LUMC

Leiden, , Netherlands

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NL-Maastricht-MUMC

Maastricht, , Netherlands

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NL-Nieuwegein-ANTONIUS

Nieuwegein, , Netherlands

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NL-Nijmegen-CWZ

Nijmegen, , Netherlands

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NL-Nijmegen-RADBOUDUMC

Nijmegen, , Netherlands

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NL-Roermond-LZR

Roermond, , Netherlands

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NL-Roosendaal-BRAVIS

Roosendaal, , Netherlands

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NL-Rotterdam-EMCDANIEL

Rotterdam, , Netherlands

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NL-Rotterdam-ERASMUSMC

Rotterdam, , Netherlands

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NL-Rotterdam-IKAZIA

Rotterdam, , Netherlands

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NL-Rotterdam-MAASSTADZIEKENHUIS

Rotterdam, , Netherlands

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NL-Rotterdam-SFG

Rotterdam, , Netherlands

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NL-Sittard-Geleen-ZUYDERLAND

Sittard, , Netherlands

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NL-Spijkenisse-SPIJKENISSEMC

Spijkenisse, , Netherlands

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NL-Terneuzen-ZORGSAAM

Terneuzen, , Netherlands

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NL-Den Haag-HAGA

The Hague, , Netherlands

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NL-Tilburg-ETZ

Tilburg, , Netherlands

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NL-Utrecht-DIAKONESSENUTRECHT

Utrecht, , Netherlands

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NL-Utrecht-UMCUTRECHT

Utrecht, , Netherlands

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NL-Venlo-VIECURI

Venlo, , Netherlands

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NL-Winterswijk-SKBWINTERSWIJK

Winterswijk, , Netherlands

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NL-Zwolle-ISALA

Zwolle, , Netherlands

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Helse Sunnmore

Ålesund, , Norway

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Haukeland University Hospital

Bergen, , Norway

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Forde Central Hosiptal

Førde, , Norway

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Harstad University Hospital

Harstad, , Norway

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Sørlandet Hospital

Kristiansand, , Norway

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Levanger Hospital

Levanger, , Norway

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NO-Lørenskog-AKERSHUS

Lørenskog, , Norway

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NO-Oslo-OSLOUH

Oslo, , Norway

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Baerum hospital

Sandvika, , Norway

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NO-Stavanger-HELSESTAVANGER

Stavanger, , Norway

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NO-Tromsø-NORTHNOORWEGEN

Tromsø, , Norway

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NO-Trondheim-STOLAV

Trondheim, , Norway

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Francisco Gentil

Lisbon, , Portugal

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SE-Boras-SASBORAS

Borås, , Sweden

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Eskilstuna Malar Hospital

Eskilstuna, , Sweden

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Falun Hospital

Falun, , Sweden

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Sahlgrenska University Hospital

Gothenburg, , Sweden

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Hallands Hospital Halmstad

Halmstad, , Sweden

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Helsingborg General Hospital

Helsingborg, , Sweden

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Ryhov Hospital

Jönköping, , Sweden

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Lidkoping Hospital

Lidköping, , Sweden

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SE-Linköping-REGIONOSTERGOTLAND

Linköping, , Sweden

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SE-Luleå-SUNDERBY

Luleå, , Sweden

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SE-Lund-SUH

Lund, , Sweden

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Orebro University Hospital

Örebro, , Sweden

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SE-Stockholm-KAROLINSKAHUDDINGE

Stockholm, , Sweden

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Sundsvall Hospital

Sundsvall, , Sweden

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Uddevall Hospital

Uddevalla, , Sweden

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Umea University Hospital

Umeå, , Sweden

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SE-Uppsala-UPPSALAUH

Uppsala, , Sweden

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Centrallasareltet Vaxjo

Vaxjo, , Sweden

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CH-Aarau-KSA

Aarau, , Switzerland

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CH-Basel-USB

Basel, , Switzerland

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CH-Bellinzona-IOSI

Bellinzona, , Switzerland

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CH-Bern-INSEL

Bern, , Switzerland

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KS Graubunden

Chur, , Switzerland

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CH-Geneve (14)-HCUGE

Geneva, , Switzerland

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Kantonsspital Baselland

Liestal, , Switzerland

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CH-Luzern-LUKS

Lucerne, , Switzerland

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CH-St. Gallen-KSSG

Sankt Gallen, , Switzerland

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CH-Zürich-USZ

Zurich, , Switzerland

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Baskent University Hospital

Adana, , Turkey (Türkiye)

Site Status

Gazi University Hospital

Ankara, , Turkey (Türkiye)

Site Status

University Hospital Ankara

Ankara, , Turkey (Türkiye)

Site Status

Istanbul University Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Ege University Hospital

Izmir, , Turkey (Türkiye)

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Erciyes University Hospital

Kayseri, , Turkey (Türkiye)

Site Status

Countries

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

References

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Mai EK, Hielscher T, Bertsch U, Salwender HJ, Zweegman S, Raab MS, Munder M, Pantani L, Mancuso K, Brossart P, Beksac M, Blau IW, Durig J, Besemer B, Fenk R, Reimer P, van der Holt B, Hanel M, von Metzler I, Graeven U, Muller-Tidow C, Boccadoro M, Scheid C, Dimopoulos MA, Hillengass J, Weisel KC, Cavo M, Sonneveld P, Goldschmidt H. Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients. Leukemia. 2024 Mar;38(3):640-647. doi: 10.1038/s41375-023-02105-6. Epub 2023 Dec 7.

Reference Type DERIVED
PMID: 38062124 (View on PubMed)

Schmitz A, Brondum RF, Johnsen HE, Mellqvist UH, Waage A, Gimsing P, Op Bruinink DH, van der Velden V, van der Holt B, Hansson M, Andersen NF, Frolund UC, Helleberg C, Schjesvold FH, Ahlberg L, Gulbrandsen N, Andreasson B, Lauri B, Haukas E, Bodker JS, Roug AS, Bogsted M, Severinsen MT, Gregersen H, Abildgaard N, Sonneveld P, Dybkaer K. Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission - results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial. BMC Cancer. 2022 Feb 5;22(1):147. doi: 10.1186/s12885-022-09184-1.

Reference Type DERIVED
PMID: 35123422 (View on PubMed)

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Related Links

Access external resources that provide additional context or updates about the study.

http://www.hovon.nl

Hovon website

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2009-017903-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMN02

Identifier Type: OTHER

Identifier Source: secondary_id

HOVON 95 MM

Identifier Type: -

Identifier Source: org_study_id

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