A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma

This is a randomized, open-label (identity of assigned treatment will be known to
participants and study staff), 3-arm (3 treatment groups), multicenter study of daratumumab
in participants diagnosed with intermediate or high-risk Smoldering Multiple Myeloma (SMM
[ie, early disease without any symptoms]). Participants will be randomized (assigned by
chance) to one of 3 treatment groups (arm A [long intense], arm B [intermediate] and arm C
[short intense]) to receive daratumumab. Each treatment group will investigate 1 of 3 dosing
schedules of daratumumab. The study will include a 28-Day Screening Phase, a Treatment Phase
of 1 to 20 treatment cycles (each cycle is 8 weeks in duration for total period of 8 to 160
weeks), and a Follow up Phase of 4-weeks from the last dose of study drug. For participants
in Arm A (long intense) and Arm B (intermediate), there is a possibility to extend treatment
with intravenous (IV) daratumumab (every 8 weeks [Q8W]) after the end of Cycle 20, as per
investigator discretion. The Follow-up Phase will continue until death, lost to follow up,
consent withdrawal, or study end, whichever occurs first. The end of the study will occur
approximately 4 years after the last participant enrolled receives a first dose of study
drug. Disease assessments will be performed every 8 weeks in the first year and then every 16
weeks until disease progression. Safety will be monitored throughout the study.

Inclusion Criteria:

- Diagnosis of smoldering multiple myeloma (SMM) for less than 5 years

- Have a confirmed diagnosis of intermediate or high-risk SMM, and an Eastern
Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion Criteria:

- Active multiple myeloma,requiring treatment as defined by the study protocol

- Primary systemic AL (immunoglobulin light chain) amyloidosis

- Prior or concurrent exposure to any of the following: approved or investigational
treatments for SMM or/and multiple myeloma, daratumumab or other anti CD-38 therapies,
treatment with corticosteroids with a dose greater than (>) 10 milligram (mg)
prednisone per day or equivalent and bone-protecting agents (eg, bisphosphonates,
denosumab) or are only allowed if given in a stable dose and for a nonmalignant
condition, or received an investigational drug (including investigational vaccines) or
used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1

- History of malignancy (other than SMM) within 3 years before the date of
randomization, except for the following if treated and not active: basal cell or
nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal
carcinoma in situ of breast, or International Federation of Gynecology and Obstetrics
(FIGO) Stage 1 carcinoma of the cervix

- Known chronic obstructive pulmonary disease (COPD) OR moderate or severe persistent
asthma within the past 2 years

- Any concurrent medical or psychiatric condition or disease (eg, autoimmune disease,
active systemic disease, myelodysplasia) that is likely to interfere with the study
procedures or results, or that in the opinion of the investigator, would constitute a
hazard for participating in this study