A Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ixazomib; Daratumumab; Dexamethasone
Intervention description: Ixazomib capsule.; Daratumumab IV infusion.; Dexamethasone tablets.
Intervention MeSH terms: Dexamethasone; Daratumumab; Ixazomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy; Ixazomib; Daratumumab; Dexamethasone

Summary:

      The purpose of this study is to evaluate the percentage of participants with a response of
      very good partial response (VGPR) or better to IDd treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have measurable disease by at least 1 of the following measurements:

               -  serum M-protein >=1 gram per liter (g/dL) (>=10 g/L).

               -  urine M-protein >=200 mg/24 hours.

          2. Have documented evidence of 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 [example, 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 per cubic millimeter (/mm^3).

               -  Platelet count >=75,000/mm^3.

               -  Total bilirubin less than or equal to (<=) 1.5*the upper limit of the normal
                  range (ULN) (except for Gilbert syndrome: direct bilirubin <=2*ULN).

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3*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
             participant 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 Cytochrome P450 3A4 (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.

               -  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
             ; participants with known human immunodeficiency virus- Ribonucleic acid (HIV-RNA)
             positivity; participants with hepatitis B virus (HBV) surface antigen or core antibody
             positivity; and participants with known hepatitis C virus-RNA positivity. Note:
             Participants who have positive hepatitis B core antibody can be enrolled but must have
             hepatitis B virus- deoxyribonucleic acid (DNA) negative. Participants who have
             positive hepatitis C antibody can be enrolled but must have hepatitis C virus-RNA
             negativity.

             Note: Participants who are already enrolled at the time of Amendment 02 should have
             local HBV testing performed as soon as possible for HBV surface antigen, e antigen,
             core antibody, and DNA. If any of these tests is positive, consult a physician with
             expertise in managing HBV for guidance regarding stopping daratumumab, starting HBV
             antiviral therapy, and remaining on study.

         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.