Phase I/II Study of Arsenic Trioxide (Trisenox), Ascorbic Acid and Bortezomib Combination Therapy in Patients With Relapsed/Refractory Multiple Myeloma
18 Years
N/A
Both
Multiple Myeloma
Trial Information
Phase I/II Study of Arsenic Trioxide (Trisenox), Ascorbic Acid and Bortezomib Combination Therapy in Patients With Relapsed/Refractory Multiple Myeloma
Despite the fact the high dose therapy and autologous transplant can prolong life in
patients with multiple myeloma (MM), in most studies there appears to be a continuously
declining event free survival following auto-transplant indicating that few patients will be
cured with this approach. A high percentage of patients the relapse in the post transplant
setting will not be candidate for additional chemotherapy. We therefore, are investigating
novel strategies for controlling their disease in the post transplant setting. The key
theoretical issue for this study is whether concomitant Trisenox would permit the use of
less toxic doses of Velcade, resulting in a less toxic but equally effective regimen.
Phase I of this study uses dose escalation to estimate the maximum tolerated dose of
Arsenic, Ascorbic Acid and Velcade. Phase II is a subsequent treatment phase using the
maximum tolerated dose from Phase I. In the absence of treatment delays due to adverse
events, treatment may continue for 6 cycles, plus two additional cycles if patient has
achieved a good response.
Inclusion Criteria:
- Diagnosis of relapsed/refractory multiple myeloma.
- Patients must have measurable disease, defined as localized plasmacytoma, detectable
M-spike by serum protein electrophoresis (SPEP) and/or urine protein electrophoresis
(UPEP), or free light chain assay, bone lytic lesions and/or bone marrow infiltration
with atypical plasma-cells.
- Patients must be at least four weeks since their prior therapy. Patients will not be
excluded because of any prior regimen they have received as long as they meet other
requirements.
- Adequate organ function, patients with elevated creatinine due to myeloma are not
excluded
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Serum potassium greater than 4.0 milliequivalent (mEq)/dL and serum magnesium greater
than 1.8 mg/dL. If these electrolytes are below the specified limits on the baseline
laboratory tests, supplemental electrolytes should be administered to bring the serum
concentrations to these levels before administering arsenic trioxide.
Exclusion Criteria:
- Patients may not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Bortezomib, Trisenox, Ascorbic acid, or other agents used in the
study.
- Corrected QT interval (QTc) interval greater than 460 msec in the presence of serum
potassium greater than or equal to 4.0 mEq/L and magnesium greater than or equal to
1.8 mg/dL, or underlying conduction disease that prevents measurement of the QTc
interval.
- History of ventricular tachycardia or any cardiac arrhythmia requiring the placement
of an automated intraventricular cardiac defibrillator or therapy with class I or
class II antiarrhythmic drug.
- Ejection fraction (EF) by multigated acquisition (MUGA) scan less than 35%.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicity
Outcome Time Frame:
30 days post last dose of study drug
Safety Issue:
Yes
Principal Investigator
Cristina Gasparetto, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Duke University
Authority:
United States: Institutional Review Board
Study ID:
Pro00008662
NCT ID:
NCT00590603
Start Date:
July 2008
Completion Date:
December 2012
Related Keywords:
- Multiple Myeloma
- Multiple myeloma
- Multiple Myeloma
- Neoplasms, Plasma Cell
Name | Location |
|---|---|
| Duke University Medical Center | Durham, North Carolina 27710 |
