This is a phase 2, single arm, open-label, multicenter study to evaluate the feasibility and tolerance of the combination of elotuzumab, lenalidomide, and dexamethasone in the induction, consolidation, and maintenance treatment of transplant eligible, newly diagnosed multiple myeloma patients.
The primary purpose of this study is to evaluate the feasibility of using the combination of elotuzumab, lenalidomide, and dexamethasone (ERd) as induction therapy and the ability of the combination to facilitate the start of autologous stem cell transplantation (ASCT) in transplant-eligible patients newly diagnosed with multiple myeloma. In addition to induction, the efficacy, safety, and tolerability of ERd as consolidation and maintenance therapy in these patients will be observed. Eligible patients will undergo four 28-day cycles of an induction regimen of elotuzumab, lenalidomide, and dexamethasone. Following completion of 4 cycles of induction therapy, all patients will undergo standard mobilization, collection of stem cells, and then ASCT using a melphalan conditioning regimen as per institutional guidelines. Toxicity evaluation will be interrupted during the stem cell procedure and will resume with the onset of consolidation. Adverse events will be collected, however, from the end of induction up to mobilization. Consolidation therapy will begin 70 to 120 days following ASCT and will consist of four 28-day cycles of elotuzumab, lenalidomide, and dexamethasone. All patients that do not experience progressive disease will begin maintenance therapy of elotuzumab, lenalidomide, and dexamethasone. The duration of maintenance will be 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Given intravenously (IV)
Given by IV
Given orally (PO) or by IV
Colorado Blood Cancer Institute
Denver, Colorado, United States
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States
HCA Midwest Health/Research Medical Center
Kansas City, Missouri, United States
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Induction Feasibility Rate (IFR)
Defined as the percentage of patients who successfully complete four 28-day cycles of induction therapy with elotuzumab, lenalidomide and dexamethasone (ERd) and start autologous stem cell transplantation (ASCT).
Time frame: approximately 22 weeks (16 weeks of treatment and 6 weeks allowance for planning and scheduling mobilization and ASCT).
Complete Response Rate (CRR) for Complete Time on Study
Defined as the percentage of patients who achieve a complete response (CR) or near complete response (nCR) to treatment at each stage of the study (induction, ASCT, consolidation, end of study) per International Myeloma Working Group (IMWG) and European Group for Blood and Marrow Transplantation (EBMT) criteria.CR=bone marrow contains ≤5% plasma cells; negative immunofixation on serum and urine; disappearance of soft tissue plasmacytomas. nCR = the absence of myeloma protein on electrophoresis, with positive immunofixation, stable bone disease, and a normal serum calcium concentration. Patient must have completed at least 1 cycle to be included in analysis.
Time frame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
Overall Response Rate (ORR) for Complete Time on Study
Defined as percentage of patients receiving at least 1 cycle with confirmed complete response, very good partial response, or partial response (CR, VGPR, or PR) to treatment at each stage of the study (induction, ASCT, consolidation, end of study) per IMWG and EBMT criteria. CR=bone marrow contains ≤5% plasma cells; negative fixation on serum and urine; the disappearance of soft tissue plasmacytomas. VGPR=serum and urine M-protein detectable by immunofixation but not by electrophoresis or ≥90% reduction from baseline serum and urine M-protein level \<100mg for 24h and In case of presence of soft tissue plasmacytoma(s) at baseline, the disappearance of any soft tissue plasmacytomas. PR=≥50% reduction from baseline in serum M-protein and ≥90% reduction from baseline in 24h urinary M-protein or urine M-protein \<200 mg/24 hours and In case of presence of soft tissue plasmacytoma(s) at baseline, a reduction in the sum of products of the two longest perpendicular diameters (SPD) by \>50%.
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Tennessee Oncology
Chattanooga, Tennessee, United States
Tennessee Oncology
Nashville, Tennessee, United States
Time frame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
Progression-free Survival (PFS)
The time from start of induction treatment to documented progressive disease (PD) or death from any cause up to 3 years post first study treatment. PD is defined as an increase of ≥ 25% from the nadir in at least one of the following criteria: serum M-protein (absolute increase must be ≥0.5 g/dL); urine M-protein (absolute increase must be ≥200 mg/24h) ; only in patients with non-measurable serum and urine M-protein levels: difference in involved and uninvolved FLC levels (absolute increase must be \>10 mg/dL); only in patients with non-measurable serum and urine M-protein levels and non-measurable disease by FLC levels, bone marrow plasma cell % (absolute % must be ≥10%) OR Definite development of new bone lesions or soft tissue plasmacytomas OR definite increase in the size of existing bone lesions or soft tissue plasmacytomas OR Development of hypercalcemia (corrected serum Ca \>11.5mg/dL) for patients without hypercalcemia at baseline. Must have completed 1 cycle to be included.
Time frame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
Overall Survival (OS)
Defined as the time from start of induction treatment to 3 years post first study treatment or death from any cause, whichever comes first. Patient must have completed at least 1 cycle to be included in analysis.
Time frame: every 4 weeks until end of treatment visit, and up to 3 years thereafter
Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety
Safety data and abnormal lab values and abnormal vital signs were collected and assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V4.03).
Time frame: weekly for 8 weeks, then every 2 weeks till the start of mobilization for Induction and 70-120 days post-ASCT, every 2 weeks during 16 weeks of Consolidation, and monthly for 24 months of Maintenance, up to 30 days after last dose of study drugs.
Consolidation Feasibility Rate (CFR)
defined as the percentage of patients starting induction treatment with ERd successfully completing treatment to end of consolidation
Time frame: approximately 55 weeks (16 weeks of induction treatment, 6 weeks allowance for planning and scheduling mobilization and ASCT, 17 weeks pause in treatment after ASCT, 16 weeks of consolidation treatment).
Maintenance Feasibility Rate (MFR)
defined as the percentage of patients starting induction treatment with ERd successfully completing treatment to end of maintenance
Time frame: approximately 159 weeks (16 weeks of induction treatment, 6 weeks allowance for planning and scheduling mobilization and ASCT, 17 weeks pause in treatment after ASCT, 16 weeks of consolidation treatment, 104 weeks/2 years of maintenance treatment)