LCI-HEM-MYE-CRD-002: Carfilzomib-Revlimid-Dexamethasone-Elotuzumab in Relapsed/Refractory Multiple Myeloma

Inclusion Criteria

Subject must meet all of the following applicable inclusion criteria to participate in this study:

• Written informed consent and HIPAA authorization for release of personal health information signed by the subject or his/her legally authorized representative.
• Age >= 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (see Appendix A, Section 18.1).
• Documented history of relapsed and/or refractory multiple myeloma per IMWG 2016 criteria [22] as defined below (biochemical and/or clinical relapse per IMWG criteria); (NOTE: subjects refractory to bortezomib and/or lenalidomide are eligible; subjects who previously received carfilzomib are eligible provided they experienced a minimal response or better and relapsed >60 days after completion of treatment [see exclusion criteria #2]):
• Relapse is defined as progression of disease after an initial response to previous treatment, more than 6 months after discontinuation of treatment.
• Refractory is defined as lack of response to previous treatment, progression of disease during treatment, or progression of disease within 6 months of discontinuation of treatment.
• Prior treatment with one line (and no more than one line) of systemic therapy for MM; NOTE: A new line of therapy is considered to start when a planned course of therapy is modified to include other treatment agents (alone or in combination) as a result of progressive disease (PD), relapse, or toxicity or when a planned period of observation off therapy is interrupted by a need for additional treatment for the disease. Induction therapy and stem cell transplant followed by planned maintenance therapy (provided there is no intervening PD) are considered to be a single line.
• Subject must have recovered from any treatment-induced toxicities to ≤ grade 1 or baseline
• Adequate washout from previous therapy:
• Prior chemotherapy is completed >3 weeks prior to day 1 of treatment (6 weeks for melphalan, nitrosoureas or monoclonal antibodies).
• Autologous transplant completed (referring to day of stem cell infusion) >12 weeks prior to day 1 of treatment; allogeneic transplant >16 weeks prior to day 1 of treatment.
• Prior radiotherapy completed at least 2 weeks prior to day 1 of treatment.
• Corticosteroid therapy at a dose equivalent to dexamethasone >4mg/day has been completed at least 2 weeks prior to day 1 of treatment.
• Measurable disease defined as:
• Serum M-protein > 0.5 g/dL OR
• Urine M-protein ≥200 mg/24 h OR
• Involved free light chain (FLC) level ≥10 mg/dL provided serum FLC ratio is abnormal.
• Demonstrate adequate organ function within 1 week of day 1 of treatment as defined in the table in Sec.tion 3.2 of protocol (#8)
• Adequate cardiac function as defined by ≥45% Left Ventricular Ejection Fraction (LVEF) by ECHO or MUGA within 28 days prior to day 1 of treatment.
• Females of childbearing potential (FCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to day 1 of treatment, and be willing to undergo serial serum or urine pregnancy testing. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause).
• FCBP must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of 1% per year] or highly effective) from the time of informed consent until 6 months after the last protocol prescribed therapy has been discontinued. NOTE: estrogens may further increase the risk of thrombosis (beyond that associated with lenalidomide) and their use should be based on a benefit-risk decision. For the highly effective contraceptive method, a method with low user dependency is preferable but not required (