Trial record 10 of 43 for:    ARSENIC ACID

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

This study has been terminated.
(Poor accrual - terminated during Phase I; Phase II never started.)
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00590603
First received: December 26, 2007
Last updated: January 7, 2014
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Arsenic Trioxide, Ascorbic Acid and Bortezomib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Arsenic Trioxide (Trisenox), Ascorbic Acid and Bortezomib Combination Therapy in Patients With Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Toxicity [ Time Frame: 30 days post last dose of study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: July 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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

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.

Other Name: AAV

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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%.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00590603

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Cephalon
Investigators
Principal Investigator: Cristina Gasparetto, MD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00590603     History of Changes
Other Study ID Numbers: Pro00008662, 7365
Study First Received: December 26, 2007
Last Updated: January 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Multiple myeloma

Additional relevant MeSH terms:
Ascorbic Acid
Arsenic trioxide
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014