Smoldering Multiple Myeloma
Conditions
Interventions
investigational material(s)
Generic name etc : Daratumumab SC
INN of investigational material : Daratumumab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investi
Sponsors
Janssen Pharmaceutical K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnosis of high risk smoldering multiple myeloma (SMM) (per International Myeloma Working Group [IMWG] criteria) for less 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 () 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
Exclusion criteria
Exclusion criteria: - Multiple myeloma (MM), requiring treatment, defined by any of the following: a. 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) b. 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 >2.75mmol/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 c. Renal insufficiency, preferably determined by creatinine clearance less than (177 micromole per liter (micromol/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 d. Anemia, defined as hemoglobin 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 e. Clonal BMPC percentage >=60% f. Serum FLC ratio (involved:uninvolved) >=100 (the involved FLC must be >=100mg/L) g. More than 1 focal lesion >=5 millimeter (mm) in diameter by magnetic resonance imaging (MRI) - Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis - Exposure to any of the following: a. Prior exposure to daratumumab or prior exposure to other anti-Cluster of Differentiation 38 (anti-CD38) therapies b. 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 c. 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 d. 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 e. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Progression-free Survival (PFS) From the date of randomization to active multiple myeloma (MM) or the date of death, whichever occurs first (up to approximately 8years) efficacy Time to Biochemical or Diagnostic (SLiMCRAB) Progression Up to biochemical or diagnostic progression (up to approximately 8 years) efficacy Overall Response Rate (ORR) Up to approximately 8 years efficacy Complete Response (CR) Rate Up to apporoximately 8 years efficacy Time to First-Line Treatment for Multiple Myeloma (MM) Post-progressive disease (PD) follow-up, every 6 months until end of study (up to approximately 8 years | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Progression-Free Survival on First-Line Treatment for MM (PFS2) Post-PD follow-up, every 6 months until end of study (up to approximately 8 years) efficacy Overall Survival (OS) Throughout study, and at least every 3 months until PD; post-PD, every 6 months until end of study (up to approximately 8years) efficacy Percentage of Participants who Progress to MM With Adverse Prognostic Features At screening and PD (up to approximately 8years) pharmacokinetics Serum Daratumumab Pharmacokinetic (PK)Concentration Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks) pharmacokinetics Maximum Observed Concentration (Cmax) of Daratumumab Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks) pharmacokinetics Minimum Observed Concentration (Cmin) of Daratumumab Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks) pharmacodynamics Number of Participants With Antidaratumumab Antibodies Cycles 1,3,5,7,12, and 24: Predose on Day 1; end of treatment (28 days after the last daratumumab dose), and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks) pharmacodynamics Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Cycles 1,3,5,7,12, and 24: Predose on Day 1; end of treatment (28 days after the last daratumumab dose), and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks) efficacy Change From Baseline in European Org | — |
Countries
Asia except Japan, Europe, Japan, Oceania, South America
Outcome results
None listed