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

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.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

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.

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