Elotuzumab, Stem Cell Transplantation, Lenalidomide, and Melphalan in Treating Patients with Multiple Myeloma

Inclusion Criteria

• Subject is, in the investigator’s opinion, willing and able to comply with the protocol requirements
• Subject has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care
• Subjects with symptomatic multiple myeloma (MM) by International Myeloma Working Group (IMWG) criteria who are receiving or have completed induction chemotherapy, who have achieved at least a partial response (PR) on most recent therapy by IMWG criteria, and are eligible for auto-SCT for consolidation; a specific induction regimen is not dictated for this protocol, however, the induction regimen must not have contained melphalan (L-PAM, Alkeran)
• Eastern Cooperative Oncology Group (ECOG) performance status >= 2
• Documented evidence of newly diagnosed, symptomatic MM, by IMWG criteria within five years of enrollment
• Prior lenalidomide exposure is permitted only if the subject did not discontinue lenalidomide due to a related, grade >= 3 adverse event (AE)
• Men and women of childbearing potential (WOCBP) must be using 2 reliable methods of contraception to avoid pregnancy throughout the study for a period of at least 30 days before and 90 days after the last dose of investigational product in such a manner that the risk of pregnancy is minimized
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG); the first should be performed within 10 to 14 days and the second within 24 hours prior to the start of the study drug; a prescription for lenalidomide for a female of childbearing potential must not be issued by the prescriber until negative pregnancy tests have been verified by the prescriber
• Women must not be breastfeeding
• Men must agree to use a latex condom and a second form of birth control during sexual contact with WOCBP, even if they have had a successful vasectomy, and must agree not to donate sperm during study drug therapy and for 90 days after therapy
• Subjects must be willing to refrain from blood donations during study drug therapy and for 8 weeks after therapy

Exclusion Criteria

• Monoclonal gammopathy of undetermined significance (MGUS), Waldenstrom’s macroglobulinemia, or asymptomatic (smoldering) myeloma
• Active plasma cell leukemia (defined as either 20% of peripheral white blood cells comprised of plasma/CD138+ cells or an absolute plasma cell count of 2 x 10^9/L)
• All AEs of any prior chemotherapy, surgery, or radiotherapy not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version [v.]4.0) grade =< 2
• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Acute renal failure due solely to readily reversible causes such as hypercalcemia, hyperuricemia, dehydration, hyperviscosity, or acute tubular necrosis from nephrotoxic drugs
• Significant cardiac disease as determined by the investigator including: * Known or suspected cardiac amyloidosis * Congestive heart failure of class III or IV of the New York Heart Association (NYHA) classification * Uncontrolled angina, hypertension or arrhythmia * Myocardial infarction in the past 6 months * Any uncontrolled or severe cardiovascular disease
• Prior cerebrovascular event with persistent neurologic deficit
• Known human immunodeficiency virus (HIV) infection or active hepatitis A, B or C
• Any medical conditions that, in the investigator’s opinion, would impose excessive risk to the subject * Examples of such conditions include: ** Any uncontrolled disease, such as pulmonary disease, infection, seizure disorder ** Any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent ** Active infection that requires parenteral anti-microbial or anti-parasitic treatment
• Prior or concurrent malignancy, except for the following: * Adequately treated basal cell or squamous cell skin cancer; * Or any other cancer from which the subject has been disease-free for > 5 years
• Uncontrolled diabetes (defined as Hgb A1C > 8.0%)
• Unable to tolerate thromboembolic prophylaxis including, as clinically indicated, aspirin, Coumadin (warfarin) or dose adjusted low-molecular weight heparin
• Corrected serum calcium > 11.5 mg/dl within 2 weeks of enrollment
• Absolute neutrophil count < 1000 cells/mm^3; no granulocyte colony stimulating factors (G-CSF or GM-CSF) allowed within 1 week of enrollment; no pegylated granulocyte colony stimulating factors are allowed within 3 weeks of treatment start
• Platelets < 75,000 cell/mm^3 (75 x 10^9/L); qualifying laboratory value must occur at most recent measurement before enrollment and must be no more than 14 days before enrollment; no transfusions are allowed within 72 hours before qualifying laboratory value
• Hemoglobin < 8 g/dL; qualifying laboratory value must occur at most recent measurement before enrollment and must be no more than 14 days before enrollment; no transfusions are allowed within 72 hours before qualifying laboratory value
• Total bilirubin > 2 X upper limit of normal (ULN) , or direct bilirubin > 2.0 mg/dL (except patients with Gilbert’s syndrome, then total bilirubin greater than 2 X ULN allowed in the absence of other hepatic signs or symptoms)
• Creatinine clearance (CrCl) < 60 ml/min by Cockcroft-Gault formula
• Major surgery within 3 weeks prior to event 1
• Kyphoplasty or vertebroplasty within 1 week prior to event 1
• Prior allogeneic stem cell transplant
• Treatment with plasmapheresis within 4 weeks prior to event 1
• Prior therapy with elotuzumab or any immunomodulatory drug (IMiD) (including pomalidomide), except for prior thalidomide or lenalidomide (as defined in inclusion criteria)
• Nonsteroidal antiinflammatory drug (NSAIDs), IV contrast, aminoglycosides, or other potentially nephrotoxic drugs within 2 weeks of event 1
• Steroids within 3 weeks prior to event 1, except: * =< 10 mg prednisone or equivalent per day * Steroid with little to no systemic absorption (ie, topical or inhaled steroids)
• Known hypersensitivity to lenalidomide, dexamethasone, any excipients in the elotuzumab formulation (sodium citrate, citric acid, sucrose and polysorbate 80) or recombinant protein
• History of grade 4 rash associated with thalidomide treatment
• Women of childbearing potential (WOCBP) who are pregnant or lactating or unwilling to use 2 forms of effective birth control
• Men who are fertile and sexually active unwilling to use 2 forms of effective birth control if their partners are WOCBP
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness