The following criteria is provided for health care professionals.

INCLUSION CRITERIA:

1. Age 18 years or older.
2. Voluntary written consent
3. Female of childbearing potential must 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
   1. Agree to practice true abstinence OR
   2. Male patients, even if surgically sterilized must agree to:
      1. practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug or abstinence
4. Confirmed symptomatic Multiple Myeloma, who progress after prior exposure to both proteasome inhibitor (bortezomib, carfilzomib) and IMID (lenalidomide or pomalidomide or thalidomide); and refractory/progressive to at least one of the agents and must have measurable disease:
5. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
6. Allogeneic transplanted patients can be enrolled only if they have no ongoing transplant related side effects or GVHD).
7. Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and have recovered from clinically significant toxicities of these prior treatments.
8. Patients must meet the following clinical laboratory criteria:
   • Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3.
   • Total bilirubin < 1.5 X the upper limit of the normal range (ULN).
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 X ULN.
   • Calculated creatinine clearance ≥ 30 mL/min.

EXCLUSION CRITERIA

1. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
2. Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy.
3. Major surgery within 14 days before enrollment.
4. Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib.
5. Myeloma Central nervous system involvement.
6. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
7. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past six months.
8. Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2, strong inhibitors of CYP3A or strong CYP3A inducers
9. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
10. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
11. Known allergy to any of the study medications or their analogues
12. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
13. Diagnosed or treated for another malignancy where the expected survival is less than 2 years will be excluded.
14. Patient has ≥ Grade 2 peripheral neuropathy, or Grade 1 with pain on clinical examination during the screening period.
15. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 2 weeks of the start of this trial and throughout the duration of this trial.
16. Patients that have previously been treated with ixazomib, or participated in a study with ixazomib.