High Dose Carfilzomib for Newly Diagnosed Myeloma

Inclusion Criteria

• •Newly diagnosed patients with histologically confirmed MM based on the following criteria:
• •* Clonal plasma cells in the bone marrow
• •* Measurable disease within the past 4 weeks defined by any one of the following:
• •Serum monoclonal protein ≥ 1.0 g/dL
• •Urine monoclonal protein \>200 mg/24 hour
• •Involved serum immunoglobulin free light chain \> 10 mg/dL AND abnormal kappa/lambda ratio
• •Evidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following:
• •* Hypercalcemia: serum calcium \>0.25 mmol/L (\> 1 mg/dL) above upper limit of normal or ≥ 2.75 mmol/L (11 mg/dL)
• •* Anemia: hemoglobin value \<10 g/dL or \> 2 g/dL below lower limit of normal
• •* Bone disease: ≥ 1 lytic lesions on skeletal X-ray, CT, or PET-CT. For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells
• •* Clonal bone marrow plasma cell percentage ≥60%
• •* Involved/un-involved serum free light chain ratio ≥100 and involved free light chain \>100 mg/L.
• •* 1 focal lesion on magnetic resonance imaging study (lesion must be \>5 mm) in size
• •Creatinine Clearance ≥ 60 ml/min. CrCl can be measured or estimated using Cockcroft-Gault method
• •Age ≥ 18 years at the time of signing the informed consent documentation
• •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• •Absolute neutrophil count (ANC) ≥ 1.0 K/uL, hemoglobin ≥ 8 g/dL, and platelet count ≥ 75 K/uL, unless if cytopenias are deemed to be due disease at discretion of clinical investigator. Transfusions and growth factors are permissible.
• •Adequate hepatic function, with bilirubin \< 1.5 x the ULN, and AST and ALT \< 3.0 x ULN.
• •All study participants must be able to tolerate one of the following thromboprophylactic strategies: aspirin, low molecular weight heparin or warfarin (coumadin) or alternative anti-coagulant.
• •All study participants must be registered into the mandatory eREMS® program, and be willing and able to comply with the requirements of REMS®.
• •Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) 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. 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 successful vasectomy.
• •* A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).