Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma

Dana-Farber Cancer Institute

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: bortezomib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00153920

03-328

Details and patient eligibility

About

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.

Full description

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%.

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

66 participants in 1 patient group

bortezomib

Experimental group

Description:

Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.

Treatment:

Drug: bortezomib