Inclusion Criteria:

• Patients with relapsed and relapsed refractory myeloma may be eligible for this trial of they meet all the following entry criteria.
• Previously diagnosed with MM based on standard IMWG criteria and currently requires treatment.
• Patient has given voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
• Patient had received at least two previous therapies OR received 1 prior line of therapy if previously treated with an IMiD plus a proteasome inhibitor and has demonstrated disease progression on or within 60 days of completion of the last therapy
• Patient has measurable disease defined as at least one of the following according to Standard Diagnostic Criteria (Rajkumar 2014):
  • Serum IgG, IgA, or IgM M-protein ≥ 0.5 g/dL, or
  • Serum IgD M-protein ≥ 0.05 g/dL, or
  • Urine M protein ≥200 mg/24 hours or
  • Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)

  • Screening Laboratory evaluations within the following parameters

    • Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factors cannot be used more recently than 14 days prior to initiation of therapy)
    • Platelet count ≥ 75,000 cells/dL (75 x 109/L) (without transfusions required during the 14 days prior to initiation of therapy)
    • Hemoglobin ≥ 8.0 g/dl (RBC transfusions are permitted)
    • Total Bilirubin ≤ 1.5 X upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
    • AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN
    • Calculated creatinine clearance ≥ 45 mL/min
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • All study participants must be registered into the mandatory POMALYST REMS® program, and be willing and able to comply with the requirements of the POMALYST REMS® program.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the POMALYST REMS® program.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior exposure to ixazomib OR is refractory to pomalidomide
• Patients that have previously been treated with ixazomib, or participated in a study with ixazomib,whether treated with the agent or not, are also excluded
• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
• Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy.
• Known GI disease or is in need of, or has had a previous GI procedure that could interfere with the oral absorption or tolerance of ixazomib or pomalidomide including difficulty swallowing.
• Known central nervous system involvement.
• Systemic treatment, within 14 days before the first dose of treatment, with strong CYP3A or inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort OR systemic treatment within 14 days of the first dose of treatment with a strong inhibitor of CYP1A2 (ciprofloxacin, fluvoxamine, cimetidine, enoxacin, ethynyl estradiol, mexiletine)
• Any medical or psychiatric illness/social situation that in the Investigator's opinion, would impose excessive risk to the patient, would adversely affect his/her participating in this study or would limit compliance with study requirements.
• Any active, or uncontrolled cardiovascular conditions, including but not limited to uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, grade 3 thromboembolic event or myocardial infarction within the past 6 months.
• The following therapies within the stated time frames prior to initiation of therapy:
  • Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 21 days (42 days for nitrosoureas).
  • The use of live vaccines within 30 days.
  • ImiDs or proteasome inhibitors within 14 days.
  • Other investigational therapies and/or monoclonal antibodies within 4 weeks.
  • Prior peripheral stem cell transplant within 12 weeks.
  • Prior allogeneic stem cell transplantation with active graft-versus-host-disease.
• Currently active graft versus host disease of any stage or grade after allogeneic stem cell transplantation
• Prior major surgical procedure or radiation therapy within 14 days of initiation of therapy.
  • Those who require a limited course of radiation for management of bone pain more than 14 days out from initiation of therapy are not excluded
  • If the involved field is small, 7 days will be considered a sufficient interval between radiotherapy and administration of the ixazomib.
• Daily requirement for corticosteroids (equivalent to > 10 mg/day prednisone, though >10mg/day is acceptable if physiological levels require, so long as the dose is stable for at least 7 days prior to initiation of therapy. Inhalation corticosteroids are exempt from this criterion. -- Lower amounts of corticosteroids that are not part of a daily requirement within 14 days prior to initiating therapy
• Concurrent symptomatic amyloidosis or plasma cell leukemia
• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. -- Those who are on prophylactic antibiotics only, or on antibiotics and have confirmation of resolution of active infection are eligible.
• Known seropositive for active viral infection with human immunodeficiency virus (HIV) hepatitis B (HBV) or hepatitis C viral (HCV). Those who are seropositive because of hepatitis B vaccine are eligible. Patients who are positive for HBV core antibody or HBV surface antigen must have a negative polymerase chain reaction (PCR) result prior to enrollment. Those who are PCR positive will be excluded
• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Participants who are receiving any other investigational agents for any indication
• History of erythema multiforme or severe hypersensitivity to prior IMiD's® or those who have a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• Inability to tolerate thromboprophylaxis
• Failure to have fully recovered (≤ Grade 1 according to CTCAE v 5) from the reversible effects of prior chemotherapy
• Peripheral neuropathy must have resolved to Grade 1 toxicity or peripheral neuropathy grade 2 with no pain to be eligible
• Alopecia of any grade is eligible