A Randomized Phase I/II Study of Optimal Induction Therapy of Bortezomib, Dexamethasone and Lenalidomide with or without Elotuzumab (NSC-764479) for Newly Diagnosed High Risk Multiple Myeloma (HRMM)

Adequate marrow function within 14 days prior to registration (ANC >/= 1,000 cells/mm3, platelet count >/= 70,000 cells/mm3 for patients who have bone marrow plasmacytosis < 50%; or >/= 50,000 cells/mm3 for patients who have bone marrow plasmacytosis of >/= 50%)
Adequate hepatic function within 14 days prior to registration (total bilirubin </= 1.5 x IULN, SGOT/AST and SGPT/ALT </= 2.5 x IULN)
Adequate renal function (CrCL) >/= 30 mL/min, by a 24-hour urine collection or estimated by the Cockcroft and Gault formula) within 14 days prior to registration:
No active involvement of the central nervous system (CNS) with MM (by clinical evaluation). (Lumbar puncture only if documentation of or clinical signs or symptoms consistent with CNS involvement of MM.)
HIV+ patients must meet additional requirements within 28 days prior to registration (CD4 cells >/= 500/mm3, viral load of < 50 copies HIV mRNA/mm3 if on cART or < 25,000 copies HIV mRNA if not on cART, no zidovudine or stavudine as part of cART ).
Must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture.
Zubrod Performance Status �� 2.
>/=18 years of age.
Hepatitis B or Hepatitis C + patients must have viral load < 800,000 IU/L within 28 days prior to registration.
No POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
No clinically significant illness including uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) Class III or Class IV heart failure (see Appendix 19.2), unstable angina pectoris, myocardial infarction within the past 6 months, >/= Grade 3 cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes mellitus. Must have EKG within 28 days prior to registration.
No psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
Pts must meet pregnancy, contraception and counseling/educational requirements for lenalidomide.
No other prior malignancy except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years.
Pts must be offered participation in banking of specimens for future research.