Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma

Phase II Trial of Velcade (Bortezomib) in Patients With Previously Untreated Multiple Myeloma

Bortezomib (Velcade) has just recently been approved by the FDA for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. This study will determine if Velcade is effective in treating patients with multiple myeloma that have had no prior treatment for the disease. We will also use whole-genome scanning to identify drug response biomarkers in bone marrow samples as well as nerve fiber studies to compare nerves prior to the use of Velcade and after treatment with Velcade.

Primary Objective

• To evaluate the objective response rate (CR + PR) to bortezomib alone in patients with newly diagnosed multiple myeloma.

Secondary Objectives

• To evaluate the tolerability and toxicity.
• To evaluate time to progression.
• To assess the frequency and severity of peripheral neuropathy.
• To evaluate the impact of early intervention with dose modification and explore symptomatic treatment of peripheral neuropathy.

Exploratory Objectives

• To perform pharmacogenomic analysis of molecular markers associated with response or non-response.

Statistical Design A one stage design is used to evaluate ORR. With 60 evaluable participants, if at least 27 objective responses are observed then bortezomib will be considered promising. The probability of concluding the treatment promising is >0.95 with a true ORR of 55% and <0.07 with a true ORR of 35%.

Inclusion Criteria:

• Diagnosis of multiple myeloma based upon standard criteria
• Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of > 1 g/dl and/or urine monoclonal immunoglobulin spike of > 200mg/24 hours.
• Karnofsky performance status of > 60
• Hemoglobin > 8.0 g/dL
• AST (SGOT) < 3 x ULN
• ALT < 3 x ULN
• Total bilirubin < 2 x ULN
• Is infertile or is practicing an adequate form of contraception
• 18 years of age or older

Exclusion Criteria:

• Prior treatment with systemic chemotherapy
• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes
• Plasma cell leukemia
• Calculated or measured creatinine clearance < 30 mL/minute within 14 days of enrollment
• Grade 2 or greater peripheral neuropathy
• Hypersensitivity to bortezomib, boron or mannitol
• Severe hypercalcemia
• HIV positive
• Known active hepatitis B or C
• New York Hospital Association Class III or IV heart failure
• Second malignancy requiring concurrent treatment
• Other serious medical or psychiatric illness
• Pregnant women
• Dialysis dependent patients