The purpose of this study is to evaluate safety and effectiveness of CNTO 328 (siltuximab) when it is administered together with velcade-melphalan-prednisone (VMP) in comparison with VMP alone in participants with multiple myeloma (a type of cancer that affects the blood and bone marrow).
The study will be conducted in 2 parts (Part 1 and Part 2) and will consist of screening period up to 2 weeks; treatment period; maintenance period (CNTO 328 hereafter referred to as siltuximab) for a maximum of 18 months and follow up period until the study ends. Part 1 is an open-label (all people know the identity of the intervention), single group safety lead-in part to evaluate the safety of siltuximab. Approximately 12 patients will be treated with siltuximab in combination with VMP. If the safety profile of the combination is acceptable, the study will proceed to Part 2. Part 2 is a randomized (the study medication is assigned by chance), open-label, 2-arm (Arm A: siltuximab + VMP; Arm B: VMP alone) study. Approximately 104 patients will be equally randomized, followed by a maintenance period with siltuximab in particiants in Arm A who achieve a partial response (PR) or better. Particiants in both parts of the study will be treated up to a maximum of nine 6-week cycles provided there is no evidence of disease progression, unacceptable toxicity, or withdrawal from treatment. Study medication will be continued for at least 2 additional cycles after confirmation of complete response, and preferably for the full 9 cycles of the treatment period. Participants who will be receiving maintenance treatment after the 12-month effectiveness analysis may continue to receive treatment with siltuximab only after careful consideration by the treating physician and on evidence of clinical benefit and in the absence of unwarranted toxicities. Safety assessments will include evaluation of adverse events, clinical laboratory tests, eastern cooperative oncology group performance status, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
118
Participants will receive siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks in Part 1.
Participants will receive siltuximab 8.3 mg/kg or 11 mg/kg as a 1-hour intravenous infusion every 3 weeks for 9 cycles of treatment in Part 2, Arm A and in maintenance period.
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert in Part 1.
Unnamed facility
Boston, Massachusetts, United States
Percentage of Participants Who Achieved Complete Response (CR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria
CR was assessed using EMBT criteria: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, \<5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks.
Time frame: Up to disease progression, approximately 3 years
Percentage of Participants Who Achieved Overall Response ie, Complete Response (CR) or Partial Response (PR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria
CR or PR was assessed using EBMT criteria. CR: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, \<5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks; PR: \>=50% reduction in the level of serum monoclonal paraprotein for at least 2 determinations 6 weeks apart, if present, reduction in 24-hour urinary light chain excretion by either \>=90% or to \<200 mg for at least 2 determinations 6 weeks apart, \>=50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least 6 weeks, if skeletal survey is available: no increase in size or number of lytic bone lesions
Time frame: Up to disease progression, approximately 3 years
Percentage of Participants Who Achieved Stringent Complete Response (sCR) - International Myeloma Working Group (IMWG) Criteria
sCR was assesses by IMWG Criteria: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, \<=5% plasma cells in bone marrow, normal free light chain ratio, absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. sCR is a CR that has been confirmed by immunofixation + free light chain assay + either bone marrow immunohistochemistry or immunofluorescence
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Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection for 9 cycles of the treatment period in Part 2. It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period)
Participants will take melphalan 9 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
Participants will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally for 9 cycles of treatment period in Part 2, Arm A.
Participants will take prednisone 60 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
Participants will take prednisone 60 mg/m2 orally for 9 cycles of treatment period in Part 2, Arm A.
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert.
Participants will take melphalan 9 mg/m2 orally according to currently approved package insert.
Participants will take prednisone 60 mg/m2 orally according to the package insert.
Unnamed facility
Chapel Hill, North Carolina, United States
Unnamed facility
Philadelphia, Pennsylvania, United States
Unnamed facility
Houston, Texas, United States
Unnamed facility
Adelaide, Australia
Unnamed facility
Melbourne, Australia
Unnamed facility
Bordeaux, France
Unnamed facility
Montpellier, France
Unnamed facility
Strasbourg, France
Unnamed facility
Ahmedabad, India
...and 27 more locations
Time frame: Up to disease progression, approximately 3 years
Progression-Free Survival (PFS)
PFS was defined as the time between randomization and either disease progression or death, whichever occurred first.
Time frame: From the date of randomization until disease progression or death, whichever occurred first, as assessed up to the last efficacy assessment for disease progression (approximately 3 years)
1-year Progression-Free Survival (PFS) Rate
The 1-year PFS rate was defined as the percentage of participants surviving 1 year after randomization without disease progression or death.
Time frame: 1 year
Duration of Response (DOR)
DOR was defined as length from the earliest date a participant achieved a complete response (CR) or partial response (PR) to either date for disease progression (including relapse from CR) or the censoring date for progressive disease. Responders without disease progression were censored at the last efficacy assessment for disease progression.
Time frame: From the date participants achieved CR or PR to either date for disease progression (including relapse from CR) or the censoring date for progressive disease, as assessed Up to 30 days after last dose of study medication
1-year Survival Rate
Percentage of participants who are alive at the end of year 1 after randomization
Time frame: 1 year
Overall Survival
Overall survival is defined as the time interval in days between the date of randomization and the participant's death from any cause.
Time frame: From the date of randomization till the date of death, as assessed up to the end of study (approximately 3 years)
Change From Baseline to Cycle 9 in Global Health Status/Quality of Life Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30)
Global health status/quality of life is a subscale of the EORTC QOL C30, which comprises two questions related to overall health/quality of life during the past week. The raw score to each question ranged from 1 (very poor) to 7 (excellent). The raw mean score of health status/quality of life subscale is calculated for each participant and a linear transformation applied to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") health and quality of life.
Time frame: Baseline (Day 1 predose) and Cycle 9 (Week 54)