Phase II Study Of PS-341 For Patients With High-Risk, Newly Diagnosed Multiple Myeloma

Inclusion Criteria

Inclusion Criteria

- Diagnosis of multiple myeloma meeting the following criteria:

- Symptomatic disease diagnosed within the past 30 days

- Measurable or evaluable disease meeting at least 1 of the following criteria:

- Serum monoclonal protein ≥ 1 g/dL (measurable disease)

- Monoclonal light chain in urine protein electrophoresis ≥ 200 mg/24-hour
urine collection (measurable disease)

- Bone marrow plasmacytosis ≥ 30% (evaluable disease)

- High-risk disease, defined by ≥ 1 of the following criteria:

- Beta 2-microglobulin ≥ 5.5 μg/mL

- Plasma cell labeling index ≥ 1%

- Deletion of chromosome 13 by cytogenetic analysis

- Age>=18

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (ECOG performance
status of 3 allowed if secondary to acute bone event [i.e., fracture])

- Adequate hematopoietic,hepatic, renal, cardiovascular function:

- Platelet count ≥ 20,000/mm^3 (transfusion allowed)

- Hemoglobin ≥ 7.0 g/dL (transfusion allowed)

- Absolute neutrophil count ≥ 500/mm^3 (without growth factor support)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Aspartate aminotransferase (AST) ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- Creatinine clearance ≥ 20 mL/min

- Fertile patients must use effective contraception

- Concurrent corticosteroids allowed for treatment of chronic disorders other than
multiple myeloma (e.g., rheumatoid arthritis or adrenal insufficiency)

- Prior or concurrent bisphosphonates allowed

- Concurrent localized radiotherapy allowed upon approval by study chair

Exclusion criteria:

- Pregnant or nursing

- Positive pregnancy test

- Myocardial infarction within the past 6 months

- New York Heart Association class III or IV heart failure

- Uncontrolled angina

- Acute ischemia by electrocardiography (EKG)

- Severe uncontrolled ventricular arrhythmias

- Active conduction system abnormalities by EKG

- Cardiac amyloidosis

- Poorly controlled hypertension

- History of allergic reaction attributable to compounds containing boron or mannitol

- Greater than grade 1 peripheral neuropathy

- Other serious medical or psychiatric illness that would preclude study completion

- Prior biologic therapy for multiple myeloma

- Concurrent biologic therapy

- Concurrent pegfilgrastim

- Prior chemotherapy for multiple myeloma

- Concurrent chemotherapy

- Prior radiotherapy for multiple myeloma

- Less than 4 weeks since prior radiotherapy for plasmacytoma (e.g., solitary
plasmacytoma)

- Other concurrent antineoplastic therapy for multiple myeloma