Adjuvant Bortezomib Maintenance Therapy After Autologous Peripheral Stem Cell Transplantation in Treating Patients With Intermediate or Advanced Multiple Myeloma

OBJECTIVES:

- Determine response rate, as defined by resolution of bone marrow plasmacytosis and
monoclonal paraproteinemia, in the first year after autologous peripheral blood stem
cell transplantation in patients with intermediate or advanced multiple myeloma treated
with adjuvant bortezomib.

- Compare progression-free survival of patients treated with adjuvant bortezomib with
historical controls treated with autologous transplantation alone.

- Determine the toxicity of this drug in these patients (phase I).

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for 8
courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib 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.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2 years.

Inclusion Criteria:

- Diagnosis of intermediate or advanced multiple myeloma meeting criteria for at least
1 2 following:

- Intermediate- to high-M-component production rates (immunoglobulin [Ig]G > 5 g/dL or
immunoglobulin A (IgA) > 3 g/dL or urine M component > 4 g/24 hours)

- More than one osteolytic bone lesion or radiographic evidence of diffuse osteoporosis

- β-2 microglobulin > 3

- Nonsecretory myeloma if bone marrow plasmacytosis is greater than 30%

- Must have undergone autologous peripheral blood stem cell transplantation within the
past 3-4 months

- Age 18 to 69 years old

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 30,000/mm^3

- serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate
transaminase (SGPT) ≤ 300 IU

- Bilirubin ≤ 2 mg/dL

- Creatinine ≤ 2.0 mg/dL

- Creatinine clearance ≥ 30 mL/min

- Negative pregnancy test

- Fertile patients must use effective contraception

Exclusion Criteria:

- concurrent major cardiac disease that would preclude study participation

- concurrent major pulmonary disease that would preclude study participation

- pregnant or nursing

- peripheral neuropathy ≥ grade 2

- history of hypersensitivity to bortezomib, boron, or mannitol

- concurrent major gastrointestinal or bladder disease that would preclude study
participation

- concurrent major neurologic or psychiatric disease that would preclude study
participation

- dementia or significantly altered mental status that would preclude giving informed
consent

- prior interferon post-transplantation

- prior thalidomide post-transplantation

- prior chemotherapy post-transplantation

- prior radiotherapy post-transplantation

- prior investigational therapy post-transplantation

- prior bortezomib

- prior therapy for myeloma post-transplantation

- other concurrent anti-myeloma therapy

- other concurrent investigational therapy