Study Association of Lenalidomide, Ixazomib, Dexamethasone and Daratumumab in Newly Diagnosed Standard Risk Multiple Myeloma

Inclusion Criteria:

• De novo symptomatic myeloma on the International Myeloma Working Group DiagnosticCriteria for the Diagnosis of Multiple Myeloma

• Measurable disease requiring systemic therapy defined by serum M-component ≥ 10g/l orurine M-component ≥ 200 mg/24h or involved free light level ≥ 100 mg/l

• Eastern Cooperative Oncology Group performance status 0, 1 or 2

• Eligible to high dose therapy

Exclusion Criteria:

• Previously treated with any systemic therapy for multiple myeloma

• Clinical signs of central nervous system involvement

• Renal insufficiency defined as estimated Glomerular Filtration Rate lower or equal to 40 ml/min/1.73 m2

• Hepatic impairment defined as aspartate transminase or alanine transaminase greater orequal to 3 x upper limit of normal, or Total bilirubin greater or equal to 3 x upperlimit of normal

• Platelet count < 75,000 per µL

• Absolute neutrophil count ≤ 1,000 cells/mm3

• Evidence of current uncontrolled cardiovascular conditions

• Female patients who are both lactating and breastfeeding or have a positive serumpregnancy test during the screening

• Infection requiring systemic antibiotic therapy or other serious infection within 14days before first dose of study drug

• Grade 3 or higher peripheral neuropathy, or grade 2 with pain, on clinical examinationduring the screening period

• Known or suspected chronic obstructive pulmonary disease with a Forced ExpiratoryVolume in 1 second < 50% of predicted normal

• Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin,carbamazepine, phenytoin, phenobarbital), or use of St. John's wort within 14 daysbefore initiation of the study drug