Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Part 1: Daratumumab; Part 2: Daratumumab; Methylprednisolone; Dexamethasone
Intervention description: First participant will receive intravenous (injection of a substance into a vein) 0.005 milligram per kilogram (mg/kg) (planned dose) infusion of daratumumab and other participants will receive different doses. The participants will receive 7 full infusions of daratumumab and 2 predose infusions every 2 weeks. The dose of daratumumab will be escalated sequentially and considering the safety and efficacy of dose in Part 1, dose for Part 2 of the study will be decided. A predose infusion of 10% of the full dose of daratumumab will be administered a day before the first 2 full infusions.; In Part 2, the participants will receive dose of daratumumab as determined in part 1 (16 mg/kg) of the study. Participants will receive 8 full infusions at weekly intervals followed by biweekly (every 2 weeks) infusions for 16 additional weeks and monthly infusions until disease progression or unmanageable toxicity, whichever comes first. Predose was dropped at some point in Part 2. A predose infusion of 10 mg daratumumab will be administered on the day before the first full infusion in select cohorts.; Pre-dose: Participants (part 1) will receive methylprednisolone 80 mg intravenous (IV) injection 30 minutes to 2 hours before treatment. Participants (part 2) will receive 100 mg methylprednisolone IV 60 minutes to 2 hours before treatment; if a patient experiences no significant infusion-related reactions, the dose of methylprednisolone may be decreased to 50 mg after Visit 4.
Post-dose: All participants (part 1) will receive 40 mg methylprednisolone orally on the first and the second day after all full infusions. During Part 2, all participants will receive 20-25 mg methylprednisolone orally or equivalent on the first and second days after all full-dose infusions.; Participants (Part 2) will receive 20 mg dexamethasone intravenous (IV) injection pre-dose, on the first and second days after every full-dose infusions.
Intervention MeSH terms: Dexamethasone; Methylprednisolone; Daratumumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Daratumumab; Safety; HuMax-CD38; Dose-escalation

Summary:

      Establishment of safety profile of HuMax-CD38 when given as monotherapy in participants with
      multiple myeloma relapsed from or refractory to at least 2 different cytoreductive therapies
      and without further established treatment options.
    

Eligibility criteria:

        Inclusion criteria

          -  Diagnosis of multiple myeloma (MM) requiring systemic therapy

          -  Age greater than or equal to (>=) 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Life expectancy greater than (>) 3 months

          -  Relapsed from or refractory to two or more different prior therapies

          -  Signed Informed consent

        Exclusion criteria

          -  Plasma cell leukemia defined as a plasma cell count > 2000/millimeter^3 (mm^3)

          -  Known amyloidosis

          -  Participants who previously have received an allogeneic stem cell transplant

          -  Sensory or motor neuropathy of >= grade 3

          -  Past or current malignancy

          -  Chronic or ongoing active infectious disease

          -  Clinically significant cardiac disease

          -  Significant concurrent, uncontrolled medical condition including, but not limited to,
             renal (except related to MM), hepatic, hematological except MM, gastrointestinal,
             endocrine, pulmonary, neurological, cerebral or psychiatric disease

          -  A baseline QT interval as corrected by Fridericia's formula > 470 millisecond (msec)
             for female participants or > 450 msec for male participants or a complete left bundle
             branch block (defined as a QRS interval >= 120 msec in left bundle branch block form)

          -  Hypokalemia

          -  Clinical signs of meningeal involvement of MM

          -  Known severe chronic obstructive pulmonary disease or asthma defined as forced
             expiratory volume in 1 second (FEV1) less than (<) 60 percentage (%) of expected

          -  History of significant cerebrovascular disease

          -  Known Human Immunodeficiency Virus seropositivity

          -  Positive serology for hepatitis B

          -  Screening laboratory values

          -  Concomitant corticosteroid

          -  Other chemotherapy that is or may be active against myeloma within 3 weeks prior to
             Visit 2 (Part 1) or the first dose of daratumumab (Part 2). However, corticosteroid
             for myeloma (less than a 4-day course) could be administered within 1 week before
             Visit 2 (Part 1) or the first dose of daratumumab (Part 2)

          -  Known hypersensitivity to components of the investigational product or severe allergic
             or anaphylactic reactions to humanized products

          -  Participants who have received treatment with any nonmarket drug substance within 4
             weeks before the first dose of daratumumab

          -  Current participation in any other interventional clinical trial

          -  Participants known or suspected of not being able to comply with a trial protocol
             (example, due to alcoholism, drug dependency, or psychological disorder)

          -  Breastfeeding women or women with a positive pregnancy test at Screening

          -  Women of childbearing potential not willing to use adequate contraception, defined as
             hormonal birth control or intrauterine device, during the trial and for 1 year after
             the last dose of daratumumab. For participants in the United States, the use of a
             double-barrier method is also considered adequate