A Phase III Trial on the Effect of Elotuzumab in VRD Induction /Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma

Inclusion Criteria:

• Patients meeting all of the following criteria will be considered for admission to thetrial:
• Confirmed diagnosis of untreated multiple myeloma requiring systemic therapy (diagnostic criteria (IMWG updated criteria (2014) )
• Measurable disease, defined as any quantifiable monoclonal protein value, defined byat least one of the following three measurements:
• Serum M-protein ≥ 10g/l (for IgA ≥ 5g/l)
• Urine light-chain (M-protein) of ≥ 200 mg/24 hours
• Serum FLC assay: involved FLC level ≥ 10 mg/dl provided sFLC ratio is abnormal
• Age 18 - 70 years inclusive
• WHO performance status 0-3 (WHO=3 is allowed only if caused by MM and not by co-morbidconditions)
• Negative pregnancy test at inclusion (women of childbearing potential)
• For all men and women of childbearing potential: patients must be willing and capableto use adequate contraception during the complete therapy. Patients must agree on therequirements regarding the lenalidomide pregnancy prevention programme described inchapter 6.
• All patients must
• agree to abstain from donating blood while taking lenalidomide and for 28 daysfollowing discontinuation of lenalidomide therapy
• agree not to share study drug lenalidomide with another person and to return allunused study drug to the investigator or pharmacist
• Ability of patient to understand character and individual consequences of the clinicaltrial
• Written informed consent (must be available before enrollment in the trial)

Exclusion Criteria:

• Patients presenting with any of the following criteria will not be included in thetrial:
• Patient has known hypersensitivity to any drugs given in the protocol, notablybortezomib, lenalidomide, dexamethasone and elotuzumab or to any of the constituentcompounds (incl. boron and mannitol).
• Systemic AL amyloidosis (except for AL amyloidosis of the skin or the bone marrow)
• Previous chemotherapy or radiotherapy during the past 5 years except localradiotherapy in case of local myeloma progression.
• Severe cardiac dysfunction (NYHA classification III-IV)
• Significant hepatic dysfunction (serum bilirubin ≥ 1,8mg/dl and/or ASAT and/or ALAT ≥ 2.5 times normal level), unless related to myeloma.
• Patients with renal insufficiency requiring hemodialysis
• HIV positivity
• Patients with active or history of hepatitis B or C
• Patients with active, uncontrolled infections
• Patients with peripheral neuropathy or neuropathic pain, CTC grade 2 or higher (asdefined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0)
• Patients with a history of active malignancy during the past 5 years with theexception of basal cell carcinoma of the skin or stage 0 cervical carcinoma treatedwith curative intent
• Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
• Autoimmune hemolytic anemia with positive Coombs test or immune thrombocytopenia
• Platelet count < 75 x 109/l, or, dependent on bone marrow infiltration by plasmacells, platelet count < 30 x 109/l (patients with platelet count < 75 x 109/l, but > 30 x 109/l may be eligible if percentage of plasma cells in bone marrow is ≥ 50%), (transfusion support within 14 days before the test is not allowed)
• Haemoglobin ≤ 8.0 g/dl, unless related to myeloma
• Absolute neutrophil count (ANC) < 1.0 x 10^9/l (the use of colony stimulating factorswithin 14 days before the test is not allowed), unless related to myeloma
• Pregnancy and lactation
• Participation in other clinical trials. This does not include long-term follow-upperiods without active drug treatment of previous studies during the last 6 months. No patients will be allowed to enrol in this trial more than once.