S0417 Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as thalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. It may also stop the growth of cancer by blocking blood flow to the cancer. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with thalidomide and dexamethasone may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with thalidomide and dexamethasone works in treating patients with relapsed or refractory multiple myeloma.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||S0417 A Phase II Study of Bortezomib (Velcade™, PS-341), Thalidomide, and Dexamethasone in Patients With 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
|Study Start Date:||August 2005|
|Study Completion Date:||June 2010|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
Experimental: bortezomib with thalidomide and dexamethasone
bortezomib with thalidomide and dexamethasone
induction: 1 mg/m2 IV push days 1, 4, 8, 11 every 21 daysDrug: dexamethasone
induction: 20 mg/d PO days 1, 2, 4, 5, 8, 9, 11, 12 every 21 days maintenance: 40 mg days 1-4 every 28 days until progressionDrug: thalidomide
100 mg/d PO days 1-21 every 21 days
- 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.
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|Principal Investigator:||Gordan Srkalovic, MD, PhD||Sparrow Regional Cancer Center|
|Principal Investigator:||Mohamad A. Hussein, MD||The Cleveland Clinic|