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
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
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.
Inclusion Criteria:
Symptomatic multiple myeloma, that was symptomatic at time of initial diagnosis, but may be asymptomatic at the time of registration based on induction therapy
For the original diagnosis of myeloma, patients must have met the following criteria at one point in their disease course: bone marrow plasmacytosis (>10% plasma cells or sheets of plasma cells) or a biopsy proven plasmacytoma, and evidence of end-organ damage due to multiple myeloma including anemia, hypercalcemia, bone disease (lytic bone lesions or pathologic fractures) or renal dysfunction.
Patients may have prior exposure to bortezomib
Patients must have received a minimum of 1 cycle, maximum of 6 cycles, of a dexamethasone-based regimen; patient must not have experienced progressive disease on such therapy
The following induction regimens were considered adequate for enrollment: dexamethasone alone; vincristine, doxorubicin and dexamethasone; thalidomide and dexamethasone; lenalidomide and dexamethasone; liposomal doxorubicin and dexamethasone; the combination of any of the above agents and dexamethasone; or cyclophosphamide, lenalidomide and dexamethasone
Patients must have received the minimum cumulative dose of dexamethasone of 160 mg (sum of induction treatment) with no maximum dose specified
Patients must have been offered and refused front-line stem cell transplant OR not have been eligible for front-line stem cell transplant.
Bone marrow aspiration and/or biopsy must be obtained =< 28 days prior to randomization
All tests below must be performed =< 28 days prior to randomization:
Adequate laboratory levels within 7 days prior to randomization: hemoglobin > 7 g/dL, platelet count > 75,000 cells/mm^3, absolute neutrophil count > 1000 cells/mm^3, creatinine < 2.5 mg/dL, creatinine clearance (measured or calculated) >= 60 mL/min, direct bilirubin =< 1.5 mg/dL, serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 times the upper limit of normal
Patients may be receiving bisphosphonates or erythropoietin growth factors (erythropoietic agents) for multiple myeloma
Prior palliative and/or localized radiation therapy is permitted, provided at least 14 days have passed from date of last radiation therapy to date of randomization
Patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or coumadin (patients with prior deep vein thrombosis [DVT] are eligible provided they remain on the anticoagulation regimen that was prescribed for treatment of the DVT throughout the protocol therapy)
Patients must be competent to understand the study as explained in the consent form
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking lenalidomide, and for 4 weeks after stopping treatment
Patients with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months
Age >=18 years
Exclusion Criteria:
Elkton MD, Maryland 21921, United States
Ann Arbor, Michigan 48106, United States
Springfield, Missouri 65802, United States
East Orange, New Jersey 07018-1095, United States
Mount Holly, New Jersey 08060, United States
Seattle, Washington 98109, United States