Study to Compare VMP With HDM Followed by VRD Consolidati... | NCT01208766

NCT01208766

ID	Type	Description	Link
2009-017903-28	EudraCT Number
EMN02	Other Identifier	European Myeloma Network

Status Module

Name	Class
European Myeloma Network B.V.	NETWORK
Gruppo Italiano Malattie EMatologiche dell'Adulto	OTHER
DSMM (Deutsche Studiengruppe Multiples Myelom)	UNKNOWN

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
R1: 4 cycles Bortezomib, Melphalan, Prednisone (VMP)	Active Comparator	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.	Drug: Bortezomib, Melphalan, Prednisone (VMP)
R1: 1 (2) cycle(s) HDM	Experimental	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.	Drug: 1 or 2 cycle(s) HDM (High Dose Melphalan)
R2: none	No Intervention	No consolidation, patients will continue to Lenalidomide maintenance.
R2: 2 cycles of VRD	Experimental	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.	Drug: 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bortezomib, Melphalan, Prednisone (VMP)	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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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)
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)
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 Outcomes

Measure	Description	Time Frame
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)

Eligibility Module

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:

Exclusion for randomisation 2:

Name	Affiliation	Role
Pieter Sonneveld, Prof.	Stichting Hemato-Oncologie voor Volwassenen Nederland	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
AU-Brisbane-PAH		Brisbane			Australia
AU-Canberra-CANBERRAHOSPITAL

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38062124	Derived	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.
35123422

Label	URL
Hovon website	View source

Ancestor Terms

ID	Term
D001897	Boronic Acids
D000148	Acids, Noncarboxylic
D000143	Acids
D007287	Inorganic Chemicals
D001896	Boron Compounds
D009930	Organic Chemicals
D011719	Pyrazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D010649	Phenylalanine
D024322	Amino Acids, Aromatic
D000598	Amino Acids, Cyclic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D010797	Phthalimides
D010795	Phthalic Acids
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D010881	Piperidones
D010880	Piperidines
D054833	Isoindoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D011246	Pregnadienetriols
D013259	Steroids, Fluorinated

ID	Term
D009101	Multiple Myeloma
D054219	Neoplasms, Plasma Cell

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases