This randomized phase III trial compares bortezomib, dexamethasone, and lenalidomide with bortezomib and dexamethasone to see how well they work in treating patients with multiple myeloma previously treated with dexamethasone. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bortezomib and dexamethasone is more effective with or without lenalidomide in treating multiple myeloma.
PRIMARY OBJECTIVES: I. To compare the progression-free survival (PFS) for two consolidation regimens: bortezomib, lenalidomide, and dexamethasone (VRD) versus bortezomib and dexamethasone (VD) only. SECONDARY OBJECTIVES: I. To determine the incremental ability of VRD versus VD in attaining a complete response or a very good partial response (VGPR) in patients receiving induction therapy with a dexamethasone based induction regimen. II. To compare the overall survival, measured from the time of study entry. III. Evaluate response rate and PFS according to cytogenetic category (by gene expression and fluorescence in situ hybridization \[FISH\]). IV. To evaluate the toxicity of the two regimens. V. To compare quality of life (QOL) based on the Functional Assessment of Cancer Therapy (FACT)-Neurotoxicity (Ntx) Trial Outcome Index (TOI) of patients receiving VD to those receiving VRD from registration to 6 months post consolidation treatment. VI. To examine the impact of differential treatment response (PFS), if observed, on QOL based on the FACT-Ntx TOI up to 12 months post consolidation treatment. VII. To obtain prospective data on multiple myeloma specific QOL attributes. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive bortezomib at 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11, lenalidomide orally (PO) once daily (QD) at 15 mg on days 1-14, and dexamethasone at 40 mg total dose per day PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive bortezomib at 1.3 mg/m2 IV on days 1, 4, 8, and 11 and dexamethasone at 40 mg total dose per day PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Northbay Cancer Center
Fairfield, California, United States
Kaiser Permanente
San Diego, California, United States
Stanford University Hospitals and Clinics
Stanford, California, United States
The Medical Center of Aurora
Aurora, Colorado, United States
Progression-free Survival (PFS)
Progression-free survival was defined as the time from randomization to the earliest documentation of disease progression (PD) or death. If a patient died without evidence of PD, the patient was considered an event if death occurred within 3 months of the last disease assessment. Patients who died outside of the specified interval or patients who were alive without evidence of PD were censored at the date of last disease assessment. The PFS results are based on data as of August 2012, while overall survival (OS) was updated in April 2014. Given the early termination and limited sample size, data management efforts to update PFS were not pursued.
Time frame: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years
Response Rates (Complete Response [CR] or Very Good Partial Response [VGPR])
CR: Patients with complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. To be considered CR, patients must meet all of the following criteria: * Negative immunofixation on the serum and urine at two consecutive times * Disappearance of any soft tissue plasmacytomas * ≤5% plasma cells in bone marrow * If serum and urine M protein are unmeasurable and the immunoglobulin free light chain (FLC) parameter is being used, patients must have a normal ratio of 0.26-1.65 at two consecutive times VGPR: * Serum and urine M-component detectable by immunofixation but not on electrophoresis OR * \>=90% reduction in serum M-component plus urine M-component \<100 mg per 24 hours (by SPEP and UPEP) * If the serum and urine M protein are unmeasurable and the immunoglobulin FLC parameter is being used, a \>90% decrease in the difference between involved and uninvolved FLC levels is required in place of the M protein criteria
Time frame: Assessed at the end of each cycle, every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years
Overall Survival (OS)
Overall survival is defined as the time from randomization to death or date of last known alive. The OS results are based on data as of April 2014.
Time frame: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years
Change in Quality of Life (QOL) From Baseline to 6 Months Post Consolidation as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI)
The combined score on the FACT-Ntx TOI is of interest. The FACT-Ntx TOI has 25 items and the score ranges from 0 (worst possible quality of life) -100 (best possible quality of life). The primary QOL endpoint is defined as the change in the FACT-Ntx TOI score from registration to 6 months post consolidation treatment.
Time frame: Baseline and 6 months post consolidation treatment
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