LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Study of CRD for Carfilzomib-Refractory Multiple Myeloma

Inclusion Criteria Subjects must meet all of the following criteria: 1. Documented history of relapsed and/or refractory multiple myeloma with \> 2 lines of therapy. One of the prior lines of therapy must have been a carfilzomib containing regimen with evidence of relapse or progression within the last 60 days of the carfilzomib containing regimen with a carfilzomib dose of at least 27 mg/m2. Carfilzomib containing regimen at the standard dose of 20/27 mg/m2 is acceptable. 2. Measurable disease, as defined by at least one of the following: 1. Serum monoclonal protein level ≥0.5 g/dL for IgG, IgA, or IgM disease 2. Urinary M-protein excretion of ≥200 mg over a 24-hour period 3. Involved free light chain level ≥10 mg/dL, along with an abnormal free light chain ratio 3. Adequate bone marrow reserves, as defined by the following: 1. Absolute neutrophil count (ANC) ≥1000 cells/mm3 within 1 week of the initiation of treatment 2. Platelet count of ≥75 ,000 cells/mm3 for subjects who have bone marrow plasmacytosis of \<50%, or ≥50,000 cells/mm3 for subjects who have bone marrow plasmacytosis of \>50% 4. Adequate hepatic function, as defined by the following: 1. Total bilirubin ≤ 2 times the upper limit of the institutional normal values 2. Total AST and ALT ≤ 3 times the upper limit of the institutional normal values 5. Adequate renal function, as defined by the following: creatinine clearance (CrCl) ≥ 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula. 6. Adequate cardiac function defined as LVEF ≥ 40% by MUGA, echocardiogram or cardiac MRI. 7. Be 18-75 years of age 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 9. FOCBP and male subjects who are sexually active with FOCBP must agree to use two highly effective (as determined per the Investigator) methods of contraception during the study and for 30 days (female subjects) or for 90 days (male subjects) following the last dose of study treatment including a male condom. 10. Ability to understand and the willingness to sign a written informed consent document. 11. Recovered from all reversible acute toxic effects of prior therapy (other than alopecia) to ≤ Grade 1 or baseline. Exclusion Criteria Subjects must not meet any of the following criteria: 1. Non-secretory multiple myeloma 2. Known amyloidosis 3. Known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 4. Clinically significant illness including, but not limited to the following: active systemic infection, uncontrolled hypertension (as defined by BP \> 160/90), New York Heart Association Class III and IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months of consent, uncontrolled cardiac arrhythmia, or any other condition (including laboratory abnormalities) that, in the opinion of the Investigator, places the subject at unacceptable risk for adverse outcome if he/she were to participate in the study 5. Prior cerebrovascular accident with persistent neurologic deficit. 6. Psychiatric illness/social situations that would limit compliance with study treatment and requirements 7. Pregnant or breast feeding. Females of childbearing potential (FOCBP) must have a negative serum pregnancy test within the 7 days prior to study drug administration and a negative urine pregnancy test within the 3 days prior to the first study drug administration. 8. Known human immunodeficiency virus (HIV) infection 9. Active hepatitis B and/or hepatitis C infection 10. Currently active second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Subjects are not considered to have a currently active malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for \>5 years, and are considered by their physician to be at less than 30% risk of relapse. In addition, subjects with basal cell carcinoma of the skin, superficial carcinoma of the bladder, carcinoma of the prostate with a current PSA value of \<0.5 ng/mL, or cervical intraepithelial neoplasia will be eligible. Finally, subjects who are on hormonal therapy for a history of either prostate cancer or breast cancer may enroll, provided that there has been no evidence of disease progression during the previous three years. 11. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib). 12. Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to hydration due to preexisting pulmonary or cardiac impairment including pleural effusion requiring thoracentesis or ascites requiring paracentesis. 13. Known intolerance to carfilzomib. 14. Co-administration with strong CYP3A4 inhibitors (such as, but not limited to, boceprevir, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole) as well as fluconazole (a dual inhibitor of CYP3A4 and CYP2C9).