Trisenox, Ascorbic Acid and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma (AAV)
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Arsenic Trioxide, Ascorbic Acid and Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple myeloma
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%.
Sites / Locations
- Duke University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Dose escalation study with two cohorts. A standard dose of Arsenic Trioxide will be given with escalating dose of Bortezomib.
Outcomes
Primary Outcome Measures
Toxicity
Secondary Outcome Measures
Response
Full Information
NCT ID
NCT00590603
First Posted
December 26, 2007
Last Updated
January 7, 2014
Sponsor
Duke University
Collaborators
Cephalon
1. Study Identification
Unique Protocol Identification Number
NCT00590603
Brief Title
Trisenox, Ascorbic Acid and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma
Acronym
AAV
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
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual - terminated during Phase I; Phase II never started.
Study Start Date
July 2008 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Cephalon
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Dose escalation study with two cohorts. A standard dose of Arsenic Trioxide will be given with escalating dose of Bortezomib.
Intervention Type
Drug
Intervention Name(s)
Arsenic Trioxide, Ascorbic Acid and Bortezomib
Other Intervention Name(s)
AAV
Intervention Description
Phase I/Cohort I
Loading:
Arsenic Trioxide (ATO): 0.25 mg/kg IV over 1-2 hr qd x 5 days (Monday-Friday)
Ascorbic Acid: 1000 mg by IV infusion over 15 minutes after each infusion of arsenic trioxide qd x 5 days
Maintenance cycles (21 days)
ATO: 0.25 mg/kg IV over 1-2 hr once a week x 2 weeks every 3 weeks (one cycle) for a total of 6 cycles.
Ascorbic Acid 1000mg IV will be given within 30 minutes of completion of ATO.
Bortezomib 1 mg/m2 is administered intravenously in a 3-5 second bolus on days 1, 8 of a 21-day cycle. ATO is given at least one hour prior to Bortezomib. The first cycle will start on week 2, after loading dose week.
Phase I/Cohort 1 is followed by Cohort 2. Phase II uses maximum tolerated dose from Phase I.
Primary Outcome Measure Information:
Title
Toxicity
Time Frame
30 days post last dose of study drug
Secondary Outcome Measure Information:
Title
Response
Time Frame
Approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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%.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cristina Gasparetto, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Trisenox, Ascorbic Acid and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma
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