The following criteria is provided for health care professionals.

Inclusion Criteria:

1. Have measurable disease by at least 1 of the following measurements:
   • serum M-protein ≥ 1 gm/dL (≥10 gm/L).
   • urine M-protein ≥ 200 mg/24 hours.
2. Have documented evidence of progressive disease (PD) on or after their last regimen as defined by IMWG criteria. All participants must have received between 1 to 3 prior therapies for MM (a prior therapy is defined as 2 or more cycles of therapy given as a treatment plan for MM [eg, a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplant (SCT) and then consolidation and/or maintenance therapy]).
3. Have achieved a response (partial response (PR) or better) to at least 1 prior therapy.
4. Have an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
5. Must meet the following laboratory criteria:
   • Absolute neutrophil count (ANC) ≥1000/mm3.
   • Platelet count ≥75,000/mm3.
   • Total bilirubin ≤1.5 x the upper limit of the normal range (ULN) (except for Gilbert syndrome: direct bilirubin ≤2 x ULN).
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN.
   • Calculated creatinine clearance ≥50 mL/min.

Exclusion Criteria:

1. Have undergone prior allogenic bone marrow transplantation.
2. Have received prior ixazomib at any time or daratumumab or other anti-CD38 therapies, except as part of initial therapy if this was stopped to move on to SCT and the participants did not progress on anti-CD38 treatment.
3. Are refractory to bortezomib or carfilzomib at the last exposure before this study (defined as participants having PD while receiving bortezomib or carfilzomib therapy or within 60 days after ending bortezomib or carfilzomib therapy).
4. Are planning to undergo SCT prior to PD on this study (ie, these participants should not be enrolled in order to reduce disease burden prior to transplant).
5. Are receiving systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's wort) within 14 days before randomization.
6. Has received autologous SCT within 12 weeks before the date of study treatment.
7. With known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note: FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is <50% of predicted normal.
   1. participants with Grade 2 or higher residual toxicities from prior therapy (including Grade 2 or higher peripheral neuropathy or any grade neuropathy with pain; excluding alopecia). This includes recovery from any major surgery. Note: Participants with planned surgical to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery.
8. Has uncontrolled clinically significant cardiac disease, including myocardial infarction within 6 months before date of study entry or unstable or uncontrolled angina, congestive heart failure, New York Heart Association (NYHA) Class III-IV, uncontrolled cardiac arrhythmia (Grade 2 or higher).
9. With ongoing or active systemic infection requiring intravenous (IV) medical management, known human immunodeficiency virus (HIV-RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive. Note: Participants who have positive hepatitis B core antibody can be enrolled but must have hepatitis B virus-DNA negative. Participants who have positive hepatitis C antibody can be enrolled but must have hepatitis C virus-RNA negative.
10. Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.