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

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)