S0417 Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

OBJECTIVES:

- Determine the confirmed overall response rate (complete remission, remission, and
partial remission) in patients with relapsed or refractory multiple myeloma treated with
bortezomib, thalidomide, and dexamethasone.

- Determine overall and progression-free survival of patients treated with this regimen.

- Determine the qualitative and quantitative toxic effects of this regimen in these
patients.

- Correlate, preliminarily, treatment with bortezomib with the activation of osteoblasts
in these patients.

OUTLINE: This is a multicenter study.

- Induction therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11, oral
thalidomide once daily on days 1-21, and oral dexamethasone once daily on days 1, 2, 4,
5, 8, 9, 11, and 12. Treatment repeats every 21 days until achievement of confirmed
complete remission (CR), remission (R), or partial remission (PR) OR for up to 8 courses
in the absence of disease progression or unacceptable toxicity.

Patients achieving confirmed CR, R, or PR who reach a plateau prior to receiving the maximum
8 courses of induction therapy OR who achieve confirmed CR, R, or PR after receiving the
maximum 8 courses of induction therapy proceed to maintenance therapy. Patients achieving
stable disease after receiving the maximum 8 courses of induction therapy either proceed to
maintenance therapy or receive further treatment with bortezomib, thalidomide, and
dexamethasone off-study.

- Maintenance therapy: Patients receive oral dexamethasone on days 1-4. Courses repeat
every 28 days for up to 3 years in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed within 30 days and then every 6
months for up to 5 years.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 18 months.

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