A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma

The study consists of 3 phases: Screening Phase (within 21 days prior to randomization),
Treatment Phase (Cycle 1 Day 1 to discontinuation of all study treatment), and Follow-up
Phase (from discontinuation of all study treatment up to death, lost to follow up, withdrawal
of consent, or the study ends, whichever occurs first). Treatment phase will include 2
treatments (Treatment A: participants will receive Velcade MelphalanPrednisone (VMP) alone
and Treatment B: participants will receive daratumumab in combination with VMP).Two interim
analyses are planned. The first will be to evaluate safety after a total of approximately 100
participants have been treated for at least 2 cycles or discontinued the study treatment. The
second will be to evaluate cumulative interim safety and efficacy data, and will be performed
when approximately 216 PFS events have been accumulated. The maximum duration of the study
will be 5 years after the last participant is randomized or after 330 participants have died,
whichever comes first. Efficacy will be primarily measured by comparison of PFS between the
two treatment arms. Participants' safety will be monitored throughout the study.

Inclusion Criteria:

- Participant must have documented multiple myeloma satisfying the calcium elevation,
renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria,
monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or
presence of a biopsy proven plasmacytoma, and measurable secretory disease, as
assessed by the central laboratory, and defined in protocol

- Participants who are newly diagnosed and not considered candidate for high-dose
chemotherapy with stem cell transplantation (SCT) due to: being age >=65 years, or in
participants <65 years: presence of important comorbid conditions likely to have a
negative impact on tolerability of high dose chemotherapy with stem cell
transplantation

- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0, 1, or 2

- Meet the clinical laboratory criteria as specified in the protocol

- A woman of childbearing potential must have a negative serum pregnancy test at
screening within 14 days prior to randomization

- Women of childbearing potential must commit to either abstain continuously from
heterosexual sexual intercourse or to use 2 methods of reliable birth control
simultaneously. This includes one highly effective form of contraception (tubal
ligation, intrauterine device, hormonal [birth control pills, injections, hormonal
patches, vaginal rings or implants] or partner's vasectomy) and one additional
effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical
cap). Contraception must begin prior to dosing. Reliable contraception is indicated
even where there has been a history of infertility, unless due to hysterectomy or
bilateral oophorectomy

Exclusion Criteria:

- Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of
undetermined significance, or smoldering multiple myeloma

- Participant has a diagnosis of Waldenstrom's disease, or other conditions in which IgM
M-protein is present in the absence of a clonal plasma cell infiltration with lytic
bone lesions

- Participant has prior or current systemic therapy or SCT for multiple myeloma, with
the exception of an emergency use of a short course (equivalent of dexamethasone 40
mg/day for 4 days) of corticosteroids before treatment

- Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as
defined by the national cancer institute common terminology criteria for adverse
events (NCI CTCAE) Version 4

- Participant has a history of malignancy (other than multiple myeloma) within 3 years
before the date of randomization (exceptions are squamous and basal cell carcinomas of
the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the
investigator, with concurrence with the sponsor's medical monitor, is considered cured
with minimal risk of recurrence within 3 years)

- Participant has had radiation therapy within 14 days of randomization

- Participant has had plasmapheresis within 28 days of randomization

- Participant has known chronic obstructive pulmonary disease (COPD) (defined as a
forced expiratory volume in 1 second [FEV1] <50% of predicted normal), known moderate
or severe persistent asthma within the last 2 years or currently has uncontrolled
asthma of any classification (controlled intermittent asthma or controlled mild
persistent asthma is allowed)

- Participants with known or suspected COPD must have a FEV1 test during screening

- Participant is known to be seropositive for human immunodeficiency virus (HIV), known
to have hepatitis B surface antigen positivity, or history of to have a history of
hepatitis C

- Participant has any concurrent medical or psychiatric condition or disease (example
active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary
disease) 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