RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving bortezomib as maintenance therapy after autologous stem cell transplantation may kill more cancer cells and prolong remission.

PURPOSE: Phase I/II trial to study the effectiveness of adjuvant bortezomib as maintenance therapy in treating patients who have undergone stem cell transplantation for intermediate or advanced multiple myeloma.

Condition	Treatment or Intervention	Phase
stage II multiple myeloma stage III multiple myeloma	Drug: bortezomib  Procedure: adjuvant therapy  Procedure: enzyme inhibitor therapy	Phase I Phase II

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.

Ages Eligible for Study:  18 Years   -   69 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of intermediate or advanced multiple myeloma meeting criteria for at least 1 of the following:
• Intermediate- to high-M-component production rates (immunoglobulin [Ig]G > 5 g/dL or 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

PATIENT CHARACTERISTICS: Age

• 18 to 69

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 30,000/mm^3

Hepatic

• SGOT or SGPT ≤ 300 IU
• Bilirubin ≤ 2 mg/dL

Renal

• Creatinine ≤ 2.0 mg/dL OR
• Creatinine clearance ≥ 30 mL/min

Cardiovascular

• No concurrent major cardiac disease that would preclude study participation

Pulmonary

• No concurrent major pulmonary disease that would preclude study participation

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No peripheral neuropathy ≥ grade 2
• No history of hypersensitivity to bortezomib, boron, or mannitol
• No concurrent major gastrointestinal or bladder disease that would preclude study participation
• No concurrent major neurologic or psychiatric disease that would preclude study participation
• No dementia or significantly altered mental status that would preclude giving informed consent

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics
• No prior interferon post-transplantation
• No prior thalidomide post-transplantation

Chemotherapy

• No prior chemotherapy post-transplantation

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy post-transplantation

Surgery

• Not specified

Other

• No prior investigational therapy post-transplantation
• No prior bortezomib
• No prior therapy for myeloma post-transplantation
• No other concurrent anti-myeloma therapy
• No other concurrent investigational therapy

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1678,  United States; Recruiting

Study chairs or principal investigators

Gary John Schiller, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000365583; UCLA-0306106; MILLENNIUM-MM2003
Record last reviewed:  May 2004
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00084747
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08