The following criteria is provided for health care professionals.

Inclusion Criteria:

• Diagnosis of multiple myeloma (MM) with deletion 17p (del17p) or monosomy 17 by fluorescence in situ hybridization (FISH) who have received at least one line of therapy
• Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x upper limit of normal (ULN)
• Total bilirubin =< 1.5 × the upper limit of the normal range (ULN)
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count >= 75,000/mm^3
• Hemoglobin >= 8.0 g/dL
• NOTE: white blood count and platelet count criteria must be met without any transfusion or growth factor support
• Patients with measurable disease defined as at least one of the following:
  • Serum monoclonal protein >= 1.0 g/dL by protein electrophoresis
  • > 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
  • Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Willing to follow strict birth control measures as suggested below
  • Female patients: if they are of childbearing potential (except if postmenopausal for at least 1 year before the screening visit, OR are surgically sterile), agree to one of the following:
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
    • 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
    • Male patients: even if surgically sterilized (ie, 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 [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
• Willing to provide bone marrow and blood samples for correlative research purposes

Exclusion Criteria:

• Other malignancy requiring active therapy
  • EXCEPTIONS: Non-melanoma skin cancer, ductal carcinoma in situ (DCIS) or carcinoma-in-situ of the cervix
    • NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
• Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
• Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational
  • NOTE: bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Patient has >= grade 2 peripheral neuropathy, or grade 1 with pain on clinical examination during the screening period
• Major surgery =< 14 days before study registration
• All cytochrome P450 family 2 subfamily C member 8 (CYP2C8) inhibitors, inducers, and substrates should be discontinued >= 7 days prior to registration; systemic treatment with CYP2C8 inhibitors (anastrozole, montelukast, quercetin, trimethoprim, gemfibrozil, rosiglitazone, pioglitazone), inducers (carbamazepine, phenytoin, rifabutin, rifampin), or substrates (amiodarone, repaglinide, rosiglitazone, sorafenib, torsemide) should be discontinued >= 7 days prior to registration
• Systemic treatment with strong inhibitors of cytochrome P450 family 3 subfamily A member 4 (CYP3A4) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, Gingko biloba, St. John's wort) are not allowed =< 14 days before registration
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months; Note: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
• Corrected QT (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the Screening period
  • Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG
• Known human immunodeficiency virus (HIV) positive
• Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Known allergy to any of the study medications, their analogues or excipients in the various formulations
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or idasanutlin including difficulty swallowing
• Diarrhea > grade 1, based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading, or currently taking antidiarrheals
• Need for ongoing therapeutic anticoagulation
• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Patients that have previously been treated with ixazomib, or who participated in a blinded study with ixazomib (whether treated with ixazomib or not)