Bortezomib in Treating Patients With Multiple Myeloma Who Have Undergone an Autologous Peripheral Blood Stem Cell Transplant

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of bortezomib during maintenance phase after high-dose melphalan and autologous peripheral blood stem cell transplantation in patients with multiple myeloma.
• Determine the safety and tolerability of bortezomib in these patients.

Secondary

• Determine the overall response rate, complete response rate, and response duration in patients treated with bortezomib at the MTD.

OUTLINE: This is an open-label, dose-finding study.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 or 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive de-escalating doses of bortezomib (at varying dosing schedules) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study treatment, patients are followed at 1 year.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma
• Must have completed high-dose melphalan and autologous peripheral blood stem cell transplantation

• Transplant must have been completed 30-120 days ago
• Must not be receiving maintenance therapy
• Patients must have received 200 mg/m² of melphalan intravenously as a conditioning regimen (no dose reduction allowed)
• No evidence of amyloidosis
• No available donor

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 75,000/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal
• Transaminase ≤ 3 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must have a negative HIV test
• No baseline neurological disease > grade I
• No cranial nerve palsy
• No demonstrated resistance to bortezomib
• No history of allergic reactions attributed to bortezomib, boron, or mannitol
• No cardiac arrhythmia
• No unstable angina pectoris
• No symptomatic congestive heart failure
• No ongoing or active infection
• No other uncontrolled illness
• No psychiatric illness or social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No other concurrent anticancer therapies or agents
• No other concurrent investigational agents
• Not receiving maintenance therapy after prior stem cell transplantation on another clinical trial