S0417 A Phase II Study of Bortezomib (Velcade™, PS-341), Thalidomide, and Dexamethasone in Patients With Refractory Multiple Myeloma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of multiple myeloma (MM)

- Active disease

- Relapsed or refractory disease after ≥ 1 prior therapy for MM, that may have included
autologous or allogeneic stem cell transplantation

- Relapse is defined as the occurrence of any of the following during or after
prior treatment:

- Myeloma protein level increase by > 100% from the lowest previously
recorded level

- Myeloma protein level increase above the defined response criteria for
partial remission

- Reappearance of any myeloma peak that had disappeared during the prior
treatment

- Increase in the size and number of lytic bone lesions and/or focal lesions
by x-ray, MRI, positron emission tomography, and/or CT scan

- Refractory disease is defined as no response (i.e., not achieving complete
remission, remission, or partial remission) to prior therapy

- Measurable disease

- No evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of
M-protein, and skin changes) syndrome

- Must be registered on protocol SWOG-S0334

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-2 (unless due to bone pain)

Life expectancy

- Not specified

Hematopoietic

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

- Platelet count > 50,000/mm^3

Hepatic

- AST or ALT ≤ 3 times upper limit of normal (ULN)

- Bilirubin ≤ 3 times ULN

Renal

- Creatinine clearance > 30 mL/min

Cardiovascular

- No New York Heart Association class III or IV congestive heart failure

- No myocardial infarction within the past 6 months

- No poorly controlled hypertension

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile female patients must use effective double method contraception for ≥ 4 weeks
before, during, and for ≥ 4 weeks after completion of study treatment (during and for
4 weeks after completion of study treatment for male patients)

- No blood, ova, or sperm donation during study treatment

- No active infection requiring antibiotics

- No neurotoxicity ≥ grade 2

- No diabetes mellitus

- No other serious medical or psychiatric illness that would preclude study treatment

- No other malignancy within the past 3 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

Chemotherapy

- At least 14 days since prior chemotherapy (28 days for nitrosoureas) and recovered

Endocrine therapy

- Not specified

Radiotherapy

- At least 14 days since prior radiotherapy and recovered

Surgery

- Not specified

Other

- No prior bortezomib alone or combined with thalidomide

- Concurrent participation on protocol SWOG-S0309 allowed