A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dara SC; Dara IV
Intervention description: Participants will receive a fixed dose of Dara SC as 1800 mg daratumumab with rHuPH20 2000 U/mL, once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.; Participants will receive Dara IV 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 522.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to show that subcutaneous (SC) administration of daratumumab
      co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to
      intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response
      rate (ORR) and maximum trough concentration (Ctrough).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Evidence of a response (Partial response [PR] or better based on investigator's
             determination of response by international myeloma working group [IMWG] criteria) to
             at least 1 prior treatment regimen

          -  Received at least 3 prior lines of therapy including a proteasome inhibitor (PI)
             (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an
             immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during
             the course of treatment (except for participants who discontinued either of these
             treatments due to a severe allergic reaction within the first 2 cycles/months). A
             single line of therapy may consist of 1 or more agents, and may include induction,
             hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy,
             bisphosphonate, or a single short course of corticosteroids (no more than the
             equivalent of dexamethasone 40 milligram/day [mg/day] for 4 days) would not be
             considered prior lines of therapy

          -  Documented multiple myeloma as defined by the criteria below:

               1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria

               2. Measurable disease at Screening as defined by any of the following:

                    1. Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein
                       level >=200 mg/24 hours; or

                    2. Light chain multiple myeloma without measurable disease in the serum or the
                       urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal
                       serum immunoglobulin kappa lambda FLC ratio

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

          -  Meet the clinical laboratory criteria as specified in the protocol

          -  Women of childbearing potential must have a negative urine or serum pregnancy test at
             screening within 14 days prior to randomization

        Exclusion Criteria:

          -  Received daratumumab or other anti-CD38 therapies previously

          -  Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the
             treatment, whichever is longer, before the date of randomization. The only exception
             is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40
             mg/day for a maximum of 4 days) before treatment

          -  Received autologous stem cell transplant within 12 weeks before the date of
             randomization, or the participant has previously received allogeneic stem cell
             transplant (regardless of timing)

          -  Plans to undergo a stem cell transplant prior to progression of disease on this study
             (these participants should not be enrolled to reduce disease burden prior to
             transplant)

          -  History of malignancy (other than multiple myeloma) unless all treatment of that
             malignancy was completed at least 2 years before consent and the patient 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