A Phase I/II Study of 153 Sm EDTMP (Quadramet™) and PS-341 (Velcade®) in Patients With Relapsed or Refractory Multiple Myeloma
- Determine the maximum tolerated dose of bortezomib when given together with samarium Sm
153 lexidronam pentasodium in patients with recurrent or refractory multiple myeloma.
- 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
- 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.
Masking: Open Label, Primary Purpose: Treatment
Toxicity (Phase I)
Angela Dispenzieri, MD
United States: Food and Drug Administration
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