Lenalidomide/Bortezomib/Dexamethasone & CNTO 328 in Transplant Eligible Newly Diagnosed Multiple Myeloma (MM)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label, Single-Arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment With Lenalidomide, Bortezomib, Dexamethasone and Siltuximab (CNTO 328) in Subjects With Newly Diagnosed, Previously Untreated Multiple Myeloma Requiring Systemic Chemotherapy|
- Maximum Tolerated Dose (MTD) of Siltuximab [ Time Frame: 21 days ] [ Designated as safety issue: No ]Maximum tolerated dose (MTD) defined as follows: At first dose level, if greater than 1 out of 3 patients or greater than 1 out of 6 patients experience dose limiting toxicity (DLT), the dose level exceeds the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) defined as toxicities graded in severity according to the guidelines outlined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
- Number of Participants With Response [ Time Frame: Evaluated after eight cycles of 21 days. ] [ Designated as safety issue: No ]Overall response defined as number of participants with International Myeloma Working Group Uniform Response Criteria: Complete Response (CR): Negative immunofixation serum & urine, Disappearance soft tissue plasmacytomas & =/<5% plasma cells in bone marrow; Stringent Complete Remission: CR + Normal Normal free light chain (FLC) ratio & Absence clonal cells in bone marrow by Immunohistochemistry/ immunofluorescence; Very Good Partial Response (VGPR): Serum & urine M-protein detectable by immunofixation but not on electrophoresis or 90%> reduction in serum M-protein +urine M-protein level <100mg per 24 hour; Partial Remission (PR): =/>50% reduction serum M-protein & reduction in 24-hour urinaryMprotein by >90% or to < 200mg per 24 hour, =/>50% reduction of serum M-protein & reduction in 24-hour urinary Mprotein by >90%/or <200mg, and if present at baseline, a >50% reduction in size of soft tissue plasmacytomas; Stable Disease: Not CR, VGPR, PR Or Progressive disease
|Study Start Date:||May 2012|
|Study Completion Date:||May 2014|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: Siltuximab + Bortezomib + Lenalidomide
Induction: Lenalidomide 25 mg orally Days 1-14; Bortezomib 1.3 mg/m2 intravenous Days 1, 4, 8 and 11; Dexamethasone 20 mg orally Days 1, 2, 4, 5, 8, 9, 11, 12. Siltuximab 11 mg/kg intravenous Day 1.
If delayed transplant, induction therapy continued up to 2 cycles beyond achieving a CR/nCR (minimum of 4 cycles of therapy and a maximum of 8 cycles of therapy) and then transition to maintenance regimen described below.
Maintenance therapy: Lenalidomide at last tolerated dose Day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg.
Siltuximab 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. Bortezomib at last tolerated dose Day 1 and Day 8 Dexamethasone at last tolerated dose or 20 mg weekly.
Induction Phase: 25 mg by mouth daily on Days 1-14. Maintenance Phase: at last tolerated dose from Induction Phase day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg.
Other Names:Drug: Bortezomib
Induction Phase: 1.3 mg/m2 by vein daily on Days 1, 4, 8 and 11.
Maintenance Phase: 1.3 mg/m2 by vein or last tolerated dose on Day 1 and Day 8.
Other Names:Drug: Siltuximab
Induction Phase Starting Dose: 11 mg/kg by vein on Day 1.
Maintenance Phase: 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy.
Other Names:Drug: Dexamethasone
Induction Phase: 20 mg by mouth on Days 1, 2, 4, 5, 8, 9, 11, 12.
Maintenance Phase: 20 mg by mouth on Days 1, 2, 4, 5, 8, 9, 11, 12. If participant still on Dexamethasone, when entering Maintenance Phase, dose reduced to 20 mg a week.
Other Name: DecadronBehavioral: Questionnaires
M. D. Anderson Symptom Inventory Module (MDASI-MM) completed Day 1, Day 8 of Cycle 1 - 8, and on Day 1 of Cycle 9 and beyond.
Other Name: Surveys
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01531998
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jatin J. Shah, MD||UT MD Anderson Cancer Center|