An Efficacy and Safety Study of Daratumumab in Patients With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor [PI] and Immunomodulatory Drug [IMiD]) or Are Double Refractory to a PI and an IMiD
An Efficacy and Safety Study of Daratumumab in Patients With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor [PI] and Immunomodulatory Drug [IMiD]) or Are Double Refractory to a PI and an IMiD
The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment
 regimens in participants with multiple myeloma who have received at least 3 prior lines of
 therapy (including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or are
 double refractory to a PI and an IMiD.
This is an open-label (identity of assigned study drug will be known) study of daratumumab
 for the treatment of participants with multiple myeloma who have received at least 3 prior
 lines of therapy including a PI and an IMiD or whose disease is double refractory to both a
 PI and an IMiD. Up to approximately 150 participants are to be enrolled. The study includes
 screening, treatment, and follow-up phases. Participants will receive daratumumab by
 intravenous infusion (28-day cycles) until disease progression, unacceptable toxicity, or
 other protocol-defined reasons. For all study drug administrations, participants will receive
 pre- and post-infusion medications for the prevention of infusion related reactions.
 Follow-up will continue until death, loss to follow up, consent withdrawal for study
 participation, or study end, whichever occurs first. The study will consist of 2 sequential
 parts (Part 1 and Part 2). The purpose of Part 1 is to select a dose and schedule for Part 2
 of the study. Assessment of tumor response and disease progression will be conducted
 according to IMWG response criteria. Serial pharmacokinetic blood samples and a
 pharmacogenomic blood sample will be collected. Safety will be monitored throughout the
 study. At the end of the study, participants who are benefiting from treatment with
 daratumumab will have the option to continue treatment.
Inclusion Criteria:

 -  Documented multiple myeloma according to protocol-defined criteria

 -  Evidence of disease progression on the most recent prior treatment regimen based on
 International Myeloma Working Group criteria

 -  Eastern Cooperative Oncology Group performance status score of 0, 1, or 2

 -  Laboratory values and electrocardiogram within protocol-defined parameters at
 screening

 Exclusion Criteria:

 -  Received daratumumab or other anti-CD38 therapies previously

 -  Nonsecretory multiple myeloma

 -  Previously received an allogenic stem cell transplant or has received an autologous
 stem cell transplantation within 12 weeks

 -  Exhibiting clinical signs of meningeal involvement of multiple myeloma

 -  Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma
 within 5 years

 -  Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis
 B surface and core antigens, or hepatitis C

 -  Has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome
 (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes),
 or amyloidosis