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

• Overall Response Rate Complete Remission (CR), Remission (R), and Partial Remission (PR). [ Time Frame: 1 year ] [ Designated as safety issue: No ]

  Responses are defined as follows:

  Complete Remission: Absence of bone marrow or blood findings of multiple myeloma. This includes disappearance of all evidence of serum and urine M-proteins on immunofixation electrophoresis studies. Normalization of serum concentrations of normal immunoglobulins is not required for CR. There must also be no evidence of increasing anemia. Bone marrow cellularity must be ≥ 20% with plasma cells ≤ 5%.

  Remission: A ≥ 75% reduction in the serum M-protein, and if a urine M-protein (Bence-Jones protein) is present, either a ≥ 90% reduction in this protein, or a urine M-protein < 0.2gm/day. Bone marrow plasma cells must be ≤ 5%.

  Partial Remission: A ≥ 50% reduction in the serum M-protein, and if present, a ≥ 50% reduction in the urine M-protein (Bence-Jones protein). Bone marrow plasma cells must not be increased from baseline level.

  
  

• Toxicity [ Time Frame: From date of protocol therapy start to date of protocol therapy end. ] [ Designated as safety issue: Yes ]
  To evaluate the qualitative and quantitative toxicities associated with this regimen.
  
  
• Progression-Free Survival [ Time Frame: about 12-18 months ] [ Designated as safety issue: No ]
  From date of initial registration to date of progression/relapse of disease or death from any cause, whichever came first, up to 5 years
  
  

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.