Samarium Sm 153 Lexidronam Pentasodium and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to cancer cells and not harm normal cells. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Bortezomib may also make cancer cells more sensitive to radiation therapy. Giving samarium Sm 153 lexidronam pentasodium together with bortezomib may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with samarium Sm 153 lexidronam pentasodium and to see how well they work in treating patients with relapsed or refractory multiple myeloma.
Multiple Myeloma and Plasma Cell Neoplasm
Other: immunologic technique
Radiation: samarium Sm 153 lexidronam pentasodium
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of 153 Sm EDTMP (Quadramet™) and PS-341 (Velcade®) in Patients With Relapsed or Refractory Multiple Myeloma|
- Toxicity (Phase I) [ Designated as safety issue: Yes ]
- Confirmed clinical response (complete response, very good partial response, partial response, or minimal response) (Phase II) [ Designated as safety issue: No ]
- Immunoglobulin free light chain response [ Designated as safety issue: No ]
- Changes in complete blood cell count and micronucleated reticulocyte count [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Study Completion Date:||June 2009|
|Primary Completion Date:||November 2007 (Final data collection date for primary outcome measure)|
- Determine the maximum tolerated dose of bortezomib when given together with samarium Sm 153 lexidronam pentasodium in patients with recurrent or refractory multiple myeloma. (Phase I)
- Determine the safety and tolerability of this regimen in these patients. (Phase II)
- Determine the hematologic response rate in patients treated with this regimen. (Phase II)
- Determine the rate of serum immunoglobulin light chain reduction in patients treated with this regimen.
- Assess the in vivo toxicity of this regimen to the progenitor cells by measuring complete blood cell count and micronucleated reticulocyte count in these patients.
OUTLINE: This is a phase I, pilot, open-label, dose-escalation study of bortezomib followed by a phase II study.
- Phase I: Patients receive samarium Sm 153 lexidronam pentasodium IV over 1 minute on day 1 and bortezomib IV over 3-5 seconds on days 2 and 5.
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.
- Phase II: Patients receive samarium Sm 153 lexidronam pentasodium as in phase I and bortezomib at the MTD determined in phase I .
Patients undergo blood sample collection at baseline and then on days 1-6 for correlative studies. Samples are analyzed for micronucleated reticulocyte count and immunoglobulin free light chain ratio to determine the early effects of treatment.
After completion of study treatment, patients are followed weekly for 7 weeks, monthly for 3 months and then every 3 months for a total of 3 years.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
|United States, Arizona|
|Mayo Clinic Scottsdale|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, Florida|
|Mayo Clinic - Jacksonville|
|Jacksonville, Florida, United States, 32224|
|United States, Minnesota|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Angela Dispenzieri, MD||Mayo Clinic|