A Phase I Study of Samarium Sm-153 Lexidronam Combined With Bortezomib for 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)