Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Carfilzomib 20 mg/m^2; Carfilzomib 70 mg/m^2; Dexamethasone 40 mg; Dara-SC 1800 mg; Dexamethasone 20 mg
Intervention description: Carfilzomib 20 mg/m^2 will be administered intravenously (IV).; Carfilzomib 70 mg/m^2 will be administered IV.; Dexamethasone 40 mg will be administered as IV infusion or orally.; Dara-SC 1800 mg will be administered by SC injection.; Dexamethasone 20 mg will be administered as IV infusion or orally.
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 88.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to compare the efficacy (rate of very good partial response
      [VGPR] or better as best response as defined by the International Myeloma Working Group
      [IMWG] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and
      dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple
      myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Evidence of a response (partial response or better based on investigator's
             determination of response by International Myeloma Working Group [IMWG] criteria) to
             daratumumab-containing therapy with response duration of at least 4 months

          -  Participants must have progressed from or be refractory to their last line of
             treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is
             defined as an initial response to previous treatment, followed by confirmed
             progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of
             treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction
             in M-protein or confirmed PD by IMWG criteria during previous treatment or >60 days
             after cessation of treatment

          -  Received 1 to 3 prior line(s) of treatment of which one contained daratumumab, and
             completed daratumumab at least 3 months prior to randomization. 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 per day [mg/day] for 4 days) would not be considered prior lines of
             therapy

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2

          -  Women of childbearing potential must have a negative urine or serum pregnancy test at
             screening within 14 days prior to randomization

        Exclusion Criteria:

          -  Previous treatment with daratumumab within the last 3 months prior to randomization

          -  Discontinuation of daratumumab due to a daratumumab-related adverse event (AE)

          -  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

          -  Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal
             antibodies (mAbs), human proteins, or their excipients, or known sensitivity to
             mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin
             derivative used to solubilize carfilzomib)

          -  Participant is: a) Known to be seropositive for human immunodeficiency virus (HIV)
             with one or more of the following: not receiving highly active antiretroviral therapy
             (ART), had a change in ART within 6 months of the start of screening, receiving ART
             that may interfere with study treatment, cluster of differentiation (CD)4 count <350
             (unit: cells per cubic millimeter of blood) at screening, acquired immunodeficiency
             syndrome (AIDS)-defining opportunistic infection within 6 months of start of
             screening, and not agreeing to start ART and be on ART >4 weeks plus having HIV viral
             load <400 copies/milliliters (mL) at end of 4-week period (to ensure ART is tolerated
             and HIV controlled. b) Seropositive for hepatitis B (defined by a positive test for
             hepatitis B surface antigen [HBsAg]). Participants with resolved infection (example:
             participants who are HBsAg negative but positive for antibodies to hepatitis B core
             antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must
             be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B
             virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be
             excluded. c) Known to be seropositive for hepatitis C (except in the setting of a
             sustained virologic response [SVR], defined as aviremia at least 12 weeks after
             completion of antiviral therapy)