Clinical trial NCT00590603: Trisenox, Ascorbic Acid and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma
Official title: Phase I/II Study of Arsenic Trioxide (Trisenox), Ascorbic Acid and Bortezomib Combination Therapy in Patients With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Cephalon
First posted: 2008-01-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I dose escalation study to estimate the maximum tolerated dose (MTD) of the novel combination of Arsenic, Ascorbic Acid and Velcade, followed by a phase II study conducted using the MTD estimated from the phase I portion.

Detailed description: 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.

Eligibility criteria: 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%.

Primary outcomes:
measure: Toxicity
timeFrame: 30 days post last dose of study drug
Secondary outcomes:
measure: Response
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Cristina Gasparetto, MD
role: PRINCIPAL_INVESTIGATOR
References: