A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens

The hypothesis is that the addition of daratumumab administered SC to standard MM regimens
will improve responses compared to response data observed in completed phase 3 studies
without daratumumab. Disease evaluations will include measurements of myeloma proteins, bone
marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and
measurements of serum calcium corrected for albumin. Safety will be measured by adverse
events, laboratory test results, electrocardiogram (ECGs), vital sign measurements, physical
examination findings, SC injection-site assessments, and assessment of Eastern Cooperative
Oncology Group (ECOG) performance status score. Study will consist of 3 phases (screening,
treatment and follow-up) and duration of study is approximately 3 years.

Inclusion Criteria:

- Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG)
diagnostic criteria

- Measurable, secretory disease as defined by any of the following:

1. Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0
gram per deciliter (g/dL); or

2. Urine M-protein level >= 200 milligram per 24 hours (mg/24 hours); or

3. Light chain multiple myeloma (MM), for participants without measurable disease in
the serum or urine: serum Immunoglobulin (Ig) free light chain (FLC) >= 10 mg/dL
and abnormal FLC ratio

- Meets one of the sets of the following criteria:

1. For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and
Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP)
regimen: newly diagnosed myeloma

2. For Daratumumab + lenalidomide + dexamethasone (D-Rd) and Daratumumab +
Carfilzomib + Dexamethasone (D-Kd) regimen: relapsed or refractory disease

3. D-Kd cohort: Participants must have received only 1 prior line of therapy for MM
which included at least 2 consecutive cycles of lenalidomide therapy

- Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0, 1, or 2

- During the study, and for 3 months after receiving the last dose of daratumumab, a
woman must agree not to donate eggs (ova, oocytes) and men must agree not to donate
sperm for the purposes of assisted reproduction

Exclusion Criteria:

- History of malignancy (other than MM) unless all treatment of that malignancy was
completed at least 2 years before consent and the participant has no evidence of
disease further exceptions are squamous and basal cell carcinomas of the skin and
carcinoma in situ of the cervix, or breast, or other non-invasive lesion, 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

- Exhibits clinical signs of meningeal involvement of MM

- Either of the following: a) Chronic obstructive pulmonary disease with a forced
expiratory volume in 1 second (FEV1) is less than (<) 50 percentage (%) of predicted
normal b) Moderate or severe persistent asthma, or a history of asthma within the last
2 years, or currently has uncontrolled asthma of any classification c) For D-Kd
cohort: Known infiltrative pulmonary disease or known pulmonary hypertension

- Any of the following: a) Known to be seropositive for human immunodeficiency virus; b)
Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Participants with resolved infection (participants who are HBsAg
negative but positive for antibodies to hepatitis B core antigen [Anti-HBc] and/or
antibodies to hepatitis B surface antigen [Anti-HBs]) must be screened using real-time
polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels.
Those who are polymerase chain reaction (PCR) positive will be excluded

- Known to be seropositive for hepatitis C (Anti-HCV antibody positive or HCV-RNA
quantitation positive) except in the setting of a sustained virologic response [SVR],
defined as aviremia at least 12 weeks after completion of antiviral therapy

- For D-Kd cohort only: Transthoracic echocardiogram showing left ventricular ejection
fraction (LVEF) <40%; uncontrolled hypertension, defined as an average systolic blood
pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic >99 mmHg
despite optimal treatment