A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma

Korábbi kezelés

• Exposure to any of the following:
  • Prior exposure to daratumumab or prior exposure to other anti-Cluster of Differentiation 38 (anti-CD38) therapies
  • Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory agent \[IMiDs\], or proteasome inhibitor \[PIs\]). Stable standard dosing of bisphosphonate and denosumab as indicated for osteoporosis is acceptable
  • Exposure to investigational drug (including investigational vaccines) or invasive investigational medical device for any indication within 4 weeks or 5 half-lives, whichever is longer, before Cycle 1, Day 1
  • Ongoing treatment with corticosteroids with a dose \>10 milligram (mg) prednisone or equivalent per day at the time of randomization; or \>280 mg cumulative prednisone dose or equivalent for any 4-week period in the year prior to randomization
  • Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab), immunomodulators (eg, abatacept, methotrexate, azathioprine, cyclosporine) or other treatments that are likely to interfere with the study procedures or results
• Received treatment (chemotherapy, surgery, et cetera \[etc\]) for a malignancy (other than SMM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion), which is considered cured with minimal risk of recurrence within 3 years

Más betegség

• Medical or psychiatric condition or disease (for example, active systemic disease \[including presence of auto-antibodies\], uncontrolled diabetes) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
• Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies, hyaluronidase, or other human proteins, or their excipients, or known sensitivity to mammalian-derived products (including dairy allergy)

Laborértékek

• Multiple myeloma (MM), requiring treatment, defined by any of the following:
  • Bone lesions (1 or more osteolytic lesions on low-dose whole body computed tomography \[LDCT\], positron-emission tomography with computed tomography \[PET-CT\] or CT). Participants who have benign/post-traumatic bone lesions visible on screening images as well as previous imaging, may be considered for inclusion. Details (diagnosis, location, duration) on benign/post-traumatic pre-existing bone lesions that can be seen on the screening images (example \[eg.\], old fractures) and were also present on previous imaging are to be reported in the case report form (CRF)
  • Hypercalcemia (serum calcium greater than \[\>\]0.25 millimoles per liter \[mmol/L\] \[\>1 milligram per deciliter {mg/dL}\] higher than upper limit of normal \[ULN\] or \>2.75 mmol/L \[\>11 mg/dL\]). Participants who have clinically stable hypercalcemia attributable to a disease other than multiple myeloma (eg, hyperparathyroidism) may be considered for inclusion after a case by case review by the medical monitor
  • Renal insufficiency, preferably determined by creatinine clearance less than (\<)40 milliliter per minute (mL/min) measured or estimated using the Modification of Diet in Renal Disease (MDRD), or serum creatinine \>177 micromole per liter (μmol/L). Participants who have clinically stable renal insufficiency attributable to a disease other than multiple myeloma (eg, glomerulonephritis) may be considered for inclusion after a case by case review by the medical monitor
  • Anemia, defined as hemoglobin \<10 gram per deciliter (g/dL) or \>2 g/dL below lower limit of normal or both; transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted. Participants who have clinically stable anemia attributable to a disease other than multiple myeloma (eg, thalassemia, vitamin B12 deficiency, iron deficiency) may be considered for inclusion after a case by case review by the medical monitor
  • Clonal BMPC percentage \>=60%
  • Serum FLC ratio (involved:uninvolved) \>=100 (the involved FLC must be \>=100 mg/L)
  • More than 1 focal lesion \>=5 millimeter (mm) in diameter by magnetic resonance imaging (MRI)

Egyéb

• Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis

• Diagnosis of high risk smoldering multiple myeloma (SMM) (per International Myeloma Working Group \[IMWG\] criteria) for less than or equal to (\<=) 5 years with measurable disease at the time of randomization, defined as serum M protein greater than or equal to (\>=) 10 gram per liter (g/L) or urine M protein \>= 200 milligram per 24 hours (mg/24 hours) or involved serum free light chain (FLC) \>=100 milligram per liter (mg/L) and abnormal serum FLC ratio
• Clonal bone marrow plasma cells (BMPCs) \>= 10 percentage (%); and at least 1 of the following risk factors; Serum M protein \>= 30 g/L, immunoglobulin (Ig)A SMM, immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes (only IgA, IgM, and IgG should be considered in determination for immunoparesis; IgD and IgE are not considered in this assessment), serum involved: uninvolved FLC ratio \>= 8 and less than (\<) 100, or clonal BMPCs greater than (\>) 50% to \<60% with measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use highly effective method of contraception
• A woman of childbearing potential must have a negative serum or urine pregnancy test at screening within 14 days prior to randomization
• During the study and for 3 months after receiving the last dose of daratumumab, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction