Study of Bortezomib,Lenalidomide,Dexamethasone & Elotuzumab in Newly Diagnosed MM

This research study is a Phase II clinical trial testing the safety and effectiveness of an investigational drug (in this case elotuzumab) in combination with lenalidomide, bortezomib and dexamethasone to learn more about the side effects of this regimen and whether it is effective in newly diagnosed multiple myeloma.

"Investigational" means that the drug elotuzumab and the combination of this agent with lenalidomide, bortezomib, and dexamethasone are being studied. It also means that the the U.S. Food and Drug Administration (FDA) has not yet approved elotuzumab for the treatment of cancer. The drugs, lenalidomide, bortezomib, and dexamethasone are approved by the FDA. Participants in this trial will have the option to undergo autologous stem cell transplantation (ASCT) following initial therapy with elotuzumab, lenalidomide, bortezomib, and dexamethasone. ASCT is a standard of care in the treatment of multiple myeloma. All participants, including those who undergo ASCT and those who choose not to, will receive what is referred to as "maintenance therapy" - or continuous treatment - after the initial cycles of treatment with elotuzumab, lenalidomide, bortezomib, and dexamethasone. The specific maintenance regimen will be determined by risk category.

Inclusion criteria

• Patients must meet the following criteria on screening examination to be eligible to participate in the study. All laboratory assessments should be performed within 21 days of initiation of protocol therapy unless otherwise specified.Subject is, in the investigator's opinion, willing and able to comply with the protocol requirements.
• Subject has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (see Appendix 1).
• Subject is a candidate for high-dose therapy and autologous SCT based on standard criteria at the institution where this treatment will be administered.
• Newly diagnosed untreated, symptomatic, documented MM based on standard diagnostic criteria (Rajkumar 2009) with measurable disease, defined as any of the following:

• Serum Immunoglobulin G (IgG), Immunoglobulin (A) IgA, or Immunoglobulin M (IgM) M-protein ≥ 0.5 g/dL, or
• Serum Immunoglobulin D (IgD) M-protein ≥ 0.05 g/dL, or
• Urinary M-protein excretion of more than 200 mg/24 hours, or
• Serum free light chains (FLC) of at least 100 mg/dL with an abnormal FLC ratio
• Subject agrees to refrain from blood donations during therapy on study and for 8 weeks after therapy is completed.
• Men and women, age ≥18 years or legal age of consent per local regulations (whichever is greater).
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting Lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking Lenalidomide through 90 days after the last dose of study drug. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 90 days after the last dose of study drug. All patients must be registered in and must comply with all requirements of the Revlimid Rems™ program.

Exclusion criteria

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Diagnosed with smoldering MM, monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia, Plasma cell leukemia, POEMS syndrome or amyloidosis.
• Participant has ≥ Grade 2 peripheral neuropathy on clinical examination within 21 days before initiation of protocol therapy.
• Renal insufficiency, defined as creatinine clearance < 30 mL/min (either actual or calculated value), within 21 days of initiation of protocol therapy. The Cockgroft-Gault formula should be used for calculating creatinine clearance values:

• (140-age) x Body mass (kg) x 0.85 (female) or 1.0 (male) serum creat (mg/dL) x 72
• Ideal body weight (IBW) should be used if actual body weight is > 20% above IBW
• Platelet count <75,000 cells/mm3 at time of screening evaluation. Transfusion may not be used to meet platelet eligibility criteria within 7 days of obtaining screening evaluation.
• Participants with an absolute neutrophil count (ANC) < 1000 cells/mm3 at time of screening evaluation. Growth factor may not be used to meet ANC eligibility criteria within 14 days of obtaining screening evaluation.
• Participants with hemoglobin level < 8.0 g/dL, at time of screening. Transfusion may not be used to meet eligibility criteria within 7 days of obtaining screening evaluation.
• Participants with hepatic impairment, defined as bilirubin > 1.5 x institutional upper limit of normal (ULN) or AST (Aspartate aminotransferase; SGOT), ALT (Alanine aminotransferase; SGPT), or alkaline phosphatase > 3x institutional ULN, within 21 days of initiation of protocol therapy
• Other ongoing or prior anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. q.d. or its equivalent) for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to study treatment.)
• Known significant cardiac abnormalities including:

• Congestive heart failure, New York Heart Association (NYHA) class III or IV
• Uncontrolled angina, arrhythmia or hypertension
• Myocardial infarction within the past six months
• Any other uncontrolled or severe cardiovascular condition
• Prior cerebrovascular event with residual neurologic deficit
• Serious, intercurrent illness including, but not limited to, clinically relevant active infection, known active hepatitis B or C viral infection, known HIV infection, uncontrolled diabetes mellitus, or serious co-morbid medical conditions such as chronic restrictive pulmonary disease, and cirrhosis.
• Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
• Prior malignancy (within the last 5 years) except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
• Known hypersensitivity to acyclovir or similar anti-viral drug
• Known intolerance to steroid therapy
• Contraindication or prior intolerance to thromboembolic prophylaxis with aspirin, warfarin or low-molecular weight heparin
• Participants with known brain metastases.
• Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic composition to dexamethasone, boron or mannitol.
• Female participants pregnant or breast-feeding.
• Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of the surgery.
• Participants with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff.