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
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Daratumumab 16 mg/kg (Part 1); Daratumumab 8 mg/kg (Part 1); Methylprednisolone; Acetaminophen; Diphenhydramine; Daratumumab (Part 2)
Intervention description: Daratumumab 16 mg/kg administered at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter by intravenous infusion; Daratumumab 8 mg/kg every 4 weeks (Q4W) continuously by intravenous infusion; Administered in prophylactic doses intravenously (or equivalent in accordance with local standards) prior to and after study drug administration. Intravenous administration is preferred, but oral steroids may be substituted; 650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.; 25 to 50 mg administered in prophylactic doses by mouth (or equivalent in accordance with local standards) prior to and after study drug administration.; Based on the Part 1 response rate, Group A or B treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Intervention MeSH terms: Acetaminophen; Diphenhydramine; Promethazine; Methylprednisolone; Daratumumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple myeloma; Daratumumab; Proteasome inhibitor; Immunomodulatory drug; IMiD

Summary:

      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.
    

Eligibility criteria:

        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