Samarium 153 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Diagnosed with multiple myeloma by 1 of the following criteria:
• •* Meets any 2 of the following major criteria:
• •* Plasmacytomas on tissue biopsy
• •* Bone marrow plasmacytosis (i.e., \> 30% plasma cells)
• •* Monoclonal immunoglobulin spike IgG \> 3.5 g/dL or IgA \> 2.0 g/dL by serum electrophoresis; kappa or lambda light chain excretion \> 1 g by 24-hour urine protein electrophoresis
• •* Plasmacytomas on tissue biopsy AND meets any 1 of the following minor criteria:
• •* Presence of monoclonal immunoglobulin at a lesser magnitude than given under above major criteria
• •* Lytic bone lesions
• •* Normal IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL
• •* Monoclonal immunoglobulin spike IgG \> 3.5 g/dL or IgA \> 2.0 g/dL by serum electrophoresis; kappa or lambda light chain excretion \> 1 g by 24-hour urine protein electrophoresis AND meets 1 of the following minor criteria:
• •* Bone marrow plasmacytosis (i.e., 10-30% plasma cells)
• •* Lytic bone lesions
• •* Presence of monoclonal immunoglobulin at a lesser magnitude than given under major criteria with bone marrow plasmacytosis (i.e., 10-30% plasma cells) AND meets 1 of the following minor criteria:
• •* Lytic bone lesions
• •* Normal IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL
• •Measurable disease, defined as a monoclonal immunoglobulin spike of ≥ 1 gm/dL by serum electrophoresis and/or a immunoglobulin spike of ≥ 200 mg by 24-hour urine protein electrophoresis or evidence of lytic bone disease OR
• •Nonmeasurable disease (i.e., patients with nonsecretory or oligosecretory multiple myeloma)
• •Relapsed or refractory disease
• •* Relapsed disease following a response or stable disease after prior chemotherapy (e.g., single-agent steroids, vincristine, doxorubicin, and dexamethasone \[VAD\], or melphalan and prednisone \[MP\]) or high-dose chemotherapy
• •* Refractory (i.e., failure to achieve at least complete or partial response or stable disease) to the most recent chemotherapy with or without systemic corticosteroids
• •No plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein), and skin changes (POEMS syndrome)
• •No extramedullary myeloma
• •PATIENT CHARACTERISTICS:
• •Karnofsky performance status 60-100%
• •Life expectancy \> 3 months
• •Absolute neutrophil count ≥ 1,500/mm³
• •Platelet count ≥ 75,000/mm³
• •AST and ALT ≤ 3 times upper limit of normal (ULN)
• •Bilirubin ≤ 2 times ULN (unless clearly related to disease)
• •Creatinine clearance ≥ 30 mL/min
• •* Creatinine clearance \> 15 mL/min and \< 30 mL/min due to significant myelomatous involvement of kidneys allowed at discretion of investigator
• •Sodium \> 130 mmol/L
• •No ECG evidence of acute ischemia or new conduction system abnormalities
• •No myocardial infarction within the past 6 months
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception
• •No active infection
• •No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL)
• •No New York Hospital Association class III or IV heart failure
• •No poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that would preclude study treatment
• •No known HIV history
• •No known active hepatitis B or C viral infection
• •No history of allergic reaction attributable to compounds of similar chemical or biological composition to bortezomib, boron, mannitol, ethylenediaminetetramethylenephosphonic acid (EDTMP), or phosphonates
• •No peripheral neuropathy \> grade 1
• •PRIOR CONCURRENT THERAPY:
• •At least 12 weeks since prior samarium Sm 153 lexidronam pentasodium
• •* No more than 1 prior treatment
• •At least 24 weeks since prior strontium chloride Sr 89
• •* No more than 1 prior treatment
• •No major surgery within the past 4 weeks
• •No chemotherapy within the past 3 weeks (6 weeks for nitrosoureas)
• •No corticosteroids (\> 10 mg/day prednisone or equivalent) within the past 3 weeks
• •No immunotherapy, antibody therapy, or radiotherapy (except localized radiotherapy) within the past 4 weeks
• •No other concurrent investigational agents
• •No concurrent corticosteroids (≥ 10 mg prednisone or equivalent)