Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone
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|ClinicalTrials.gov Identifier: NCT00522392|
Recruitment Status : Terminated (Slow accrual)
First Posted : August 29, 2007
Results First Posted : June 26, 2015
Last Update Posted : June 26, 2015
|Condition or disease||Intervention/treatment||Phase|
|Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma||Drug: bortezomib Drug: lenalidomide Drug: dexamethasone||Phase 3|
I. To compare the progression-free survival (PFS) for two consolidation regimens: bortezomib, lenalidomide, and dexamethasone (VRD) versus bortezomib and dexamethasone (VD) only.
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 (Clinical Trial)|
|Actual Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Phase III Trial of Consolidation Therapy With Bortezomib (Velcade®)-Lenalidomide (Revlimid®) -Dexamethasone (VRD) Versus Bortezomib (Velcade®)-Dexamethasone (VD) for Patients With Multiple Myeloma Who Have Completed a Dexamethasone Based Induction Regimen|
|Study Start Date :||September 2007|
|Actual Primary Completion Date :||August 2012|
|Actual Study Completion Date :||July 2014|
Experimental: Arm A (VRD)
Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin.
Active Comparator: Arm B (VD)
Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15.
- Progression-free Survival (PFS) [ 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 ]
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.
- Response Rates (Complete Response [CR] or Very Good Partial Response [VGPR]) [ 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 ]
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
- 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
- Overall Survival (OS) [ 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 ]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.
- 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) [ Time Frame: Baseline and 6 months post consolidation treatment ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00522392
|Study Chair:||Rafael Fonseca, M.D.||Mayo Clinic|