Trisenox, Ascorbic Acid and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma

NCT00590603 | Terminated Phase 1 DMC

• 2 other identifiers: Pro000086627365
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

Multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Toxicity

  30 days post last dose of study drug

Secondary Outcomes (1)

• Response

  Approximately 2 years

Study Arms (1)

1

EXPERIMENTAL

Dose escalation study with two cohorts. A standard dose of Arsenic Trioxide will be given with escalating dose of Bortezomib.

Drug: Arsenic Trioxide, Ascorbic Acid and Bortezomib

Interventions

Arsenic Trioxide, Ascorbic Acid and Bortezomib DRUG

Phase I/Cohort I Loading: 1. Arsenic Trioxide (ATO): 0.25 mg/kg IV over 1-2 hr qd x 5 days (Monday-Friday) 2. Ascorbic Acid: 1000 mg by IV infusion over 15 minutes after each infusion of arsenic trioxide qd x 5 days Maintenance cycles (21 days) 1. 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. 2. Ascorbic Acid 1000mg IV will be given within 30 minutes of completion of ATO. 3. 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.

Also known as: AAV

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Duke University: lead
• Cephalon: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Arsenic Trioxide; Ascorbic Acid; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Cristina Gasparetto, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 10, 2008
• Study Start: July 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 8, 2014

Record last verified: 2012-12

Locations

US (1)