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

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma (Kahler's disease)

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.

Sonia More', Alfonso Piciocchi, Samuele Confalone, Sara Bringhen, Mattia D’Agostino et al. (15 authors)

Blood2025-11-03

10.1182/blood-2025-7563

Consolidation Treatment with VRD Followed By Maintenance with Lenalidomide in Multiple Myeloma Improves Overall Survival: Long-Term Follow-up of the EMN02/HOVON95 Randomized Phase 3 Trial

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Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients.

Mai EK, Hielscher T, Bertsch U, Salwender HJ, Zweegman S, Raab MS, Munder M, Pantani L, Mancuso K, Brossart P, Beksac M, Blau IW, Dürig J, Besemer B, Fenk R, Reimer P, van der Holt B, Hänel M, von Metzler I, Graeven U, Müller-Tidow C, Boccadoro M, Scheid C, Dimopoulos MA, Hillengass J, Weisel KC, Cavo M, Sonneveld P, Goldschmidt H.

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10.1038/s41375-023-02105-6

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Consolidation Treatment with VRD Followed By Maintenance Therapy Versus Maintenance Alone in Newly Diagnosed, Transplant-Eligible Patients with Multiple Myeloma (MM): A Randomized Phase 3 Trial of the European Myeloma Network (EMN02/HO95)

Pieter Sonneveld, Meral Beksaç, Bronno van der Holt, Meletios Α. Dimopoulos, Angelo Michele Carella et al. (27 authors)

Blood2020-11-055 citations

10.1182/blood-2020-139337

Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study.

Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P.

2020-04-30279 citations

10.1016/s2352-3026(20)30099-5

Minimal residual disease by flow cytometry and allelic‐specific oligonucleotide real‐time quantitative polymerase chain reaction in patients with myeloma receiving lenalidomide maintenance: A pooled analysis

Manuela Gambella, Paola Omedè, Stefano Spada, Vittorio Emanuele Muccio, Milena Gilestro et al. (20 authors)

Cancer2018-12-1837 citations

10.1002/cncr.31854

Minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) in newly diagnosed transplant eligible multiple myeloma (MM) patients: Results from the EMN02/HO95 phase 3 trial.

Stefania Oliva, Davine Hofste op Bruinink, Lucie Říhová, Stefano Spada, Bronno van der Holt et al. (20 authors)

Journal of Clinical Oncology2017-05-2018 citations

10.1200/jco.2017.35.15_suppl.8011

Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): A randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial).

Michèle Cavo, Antonio Palumbo, Sonja Zweegman, Meletios Α. Dimopoulos, Roman Hájek et al. (20 authors)

Journal of Clinical Oncology2016-05-2065 citations

10.1200/jco.2016.34.15_suppl.8000

Interventions

DRUGBortezomib, 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

DRUG1 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.

DRUG2 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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
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 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 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

Measure	Time frame	Description
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
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.

Countries

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

Outcome results

None listed