A Study to Evaluate Dara-CyBorD in Previously Untreated and Relapsed Subjects With Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Daratumumab; Cyclophosphamide; Bortezomib; Dexamethasone
Intervention description: For induction therapy cycle 1 day 1 and day 2 doses of daratumumab will be 8 milligram/kilogram (mg/kg). Starting cycle 1 week 2 until the completion of week 8 of daratumumab patients will receive 16 mg/kg Intravenously (IV) weekly.
Starting week 9 until the completion of week 24 therapy daratumumab will be administered every other week at 16 mg/kg IV.
Starting week 25 and beyond for induction therapy daratumumab will be given once every 4 weeks.; Subjects will receive 4 to 8 cycles of oral cyclophosphamide 300 milligram per meter square (mg/m^2 ) on Days 1, 8, 15, and 22 for every 28 days.; Subjects will receive 4 to 8 cycles of Bortezomib 1.5 mg/m2 subcutaneous (SC) on Days 1, 8, and 15 for every 28 days.; Subjects will be given corticosteroids (Dexamethasone) as pre-infusion therapy prior to daratumumab and for the first 8 cycles will also receive post-infusion corticosteroids (Dexamethasone).
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Bortezomib; Daratumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate complete response plus (+) very good partial
      response (CR+VGPR) rate following 4 cycles of induction therapy of daratumumab in combination
      with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD), in previously untreated
      subjects, and in relapsed subjects with multiple myeloma, as defined by the International
      Myeloma Working Group (IMWG) criteria.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with documented multiple myeloma (MM) as defined by the International Myeloma
             Working Group (IMWG) 2015 criteria: Clonal bone marrow plasma cells greater than or
             equal to (>=) 10 percent (%) or biopsy-proven bony or extramedullary plasmacytoma and
             any one or more of the following CRAB (calcium level, renal dysfunction, anemia, and
             destructive bone lesions) features and myeloma defining events as in the protocol

          -  Subjects with previously untreated myeloma or relapsed myeloma with one prior line of
             therapy including an induction regimen which may be followed by autologous stem cell
             transplantation and single agent maintenance therapy. For previously untreated
             subjects an emergency course of steroids (defined as no greater than 40 milligram (mg)
             of dexamethasone, or equivalent per day for a maximum of 4 days) is permitted. In
             addition, radiation therapy is permitted prior to study entry, during screening, and
             during Cycles 1-2 of study treatment as needed for lytic bone disease

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or
             2

          -  A woman of childbearing potential must have 2 negative serum (beta (β) human chorionic
             gonadotropin) or urine pregnancy tests during screening, the first one within 28 days
             prior to the first dose of study drug and the second within 24 hours prior to the
             first dose of study drug

          -  A man who is sexually active with a woman of childbearing potential and has not had a
             vasectomy must agree to use a barrier method of birth control example, either condom
             with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap
             (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository,
             and all men must also not donate sperm during the study and for 3 months after
             receiving the last dose of study drug

        Exclusion Criteria:

          -  Refractory to any proteasome inhibitor (PI) or the combination of PI and
             immunomodulatory drug (IMiD) agents (such as lenalidomide), defined as failure to
             respond or progression within 60 days of the end of PI therapy

          -  Exhibiting clinical signs of or has a known history of meningeal or central nervous
             system involvement by multiple myeloma

          -  Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1
             second (FEV1) less than (<) 50 percent (%) of predicted normal

          -  Has known moderate or severe persistent asthma within the past 2 years, or currently
             has uncontrolled asthma of any classification

          -  Is known to be seropositive for human immunodeficiency virus, known to have hepatitis
             B surface antigen positivity, or known to have a history of hepatitis C