Study of Bortezomib,Lenalidomide,Dexamethasone & Elotuzumab in Newly Diagnosed MM
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide; Elotuzumab; Bortezomib; Dexamethasone; Stem Cell Mobilization
Intervention MeSH terms: Dexamethasone; Lenalidomide; Bortezomib; Elotuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma

Summary:

      This research study is evaluating a combination of four drugs -- lenalidomide, bortezomib,
      dexamethasone and elotuzumab -- as therapy for newly diagnosed multiple myeloma.
    

Eligibility criteria:

        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             understanding that consent may be withdrawn by the subject at any time without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.