A Study to Test the Combination of Selinexor (KPT-330), Ixazomib, and Dexamethasone in Patients With Myeloma

Inclusion Criteria

• •MSKCC confirmed diagnosis of multiple myeloma that has relapsed or is resistant after therapy with at least one immunomodulatory drug (i.e. lenalidomide, thalidomide) and at least one proteasome inhibitor.
• •Measurable multiple myeloma disease, defined as meeting at least 1 of the following criteria within 14 days prior to registration:
• •1. A monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of ≥ 0.5 g/dL.
• •2. Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ≥ 200 mg/24 hours.
• •3. Involved serum free light chain (FLC) level ≥ 10 mg/dL, provided the serum FLC ratio is abnormal.
• •4. Presence of extramedullary plasmacytomas.
• •Patient must be ≥ 18 years of age at time of informed consent.
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 14 days prior to registration.
• •Adequate hematology laboratory values within 14 days prior to registration:
• •* Neutrophils ≥ 1.0 × 10\^9/L (growth factor support is not allowed).
• •* Platelet count ≥75x10\^9/L. Platelet support is permitted within 14 days although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours (3 days) prior to the blood sample to confirm protocol eligibility.
• •Adequate hepatic and renal function laboratory values within 14 days prior to registration:
• •1. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3 × the upper limit of normal (ULN).
• •2. Total bilirubin ≤ 1.5 mg/dL except for patients with a history of elevated total bilirubin, such as in Gilbert's.
• •3. Calculated (Cockcroft and Gault formula) or measured creatinine clearance ≥ 30mL/min.
• •Left ventricular ejection fraction (LVEF) ≥ 40% within 28 days prior to registration, evaluated by 2-D transthoracic echocardiogram (ECHO) or, if ECHO is not available, by multi-gated acquisition (MUGA) scan.
• •Female patients who:
• •* Are postmenopausal for at least 1 year before the screening visit, OR
• •* Are surgically sterile, OR
• •* If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
• •* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)If patient is female and of childbearing potential, she must have a negative serum beta human chorionic gonadotropin (β-HCG) test within 14 days prior to registration and consent to ongoing pregnancy testing during the course of the study.
• •Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
• •* Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
• •* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
• •For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
• •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• •Written informed consent in accordance with federal, local, and institutional guidelines. The patients must provide informed consent prior to the first screening procedure.