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Velcade, Trisenox, Vitamin C and Melphalan for Myeloma Patients
This study has been completed.
First Received: May 3, 2007   Last Updated: October 22, 2009   History of Changes
Sponsor: M.D. Anderson Cancer Center
Collaborator: Cephalon
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00469209
  Purpose

Primary Objectives:

  1. To evaluate the toxicity and safety of a combination of bortezomib with arsenic trioxide, ascorbic acid and high-dose melphalan in patients with multiple myeloma
  2. To evaluate the efficacy of a combination of bortezomib with arsenic trioxide, ascorbic acid and high-dose melphalan in patients with multiple myeloma
  3. To determine the effects of bortezomib on melphalan pharmacokinetics

Condition Intervention Phase
Myeloma
Drug: Trisenox (Arsenic Trioxide)
Drug: Velcade (Bortezomib)
Drug: Melphalan
Drug: Vitamin C (Ascorbic Acid)
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title: Phase I/II Study of the Combination of Bortezomib With Arsenic Trioxide, Ascorbic Acid and High-Dose Melphalan for Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Patients Reaching Complete Response (CR) at Day 90 + Day 180 [ Time Frame: Baseline, Day 90 and Day 180 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity and safety of combination of bortezomib with arsenic trioxide, ascorbic acid and high-dose melphalan [ Time Frame: Baseline to 30 days ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: June 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
Melphalan + Arsenic Trioxide + Vitamin C
Drug: Trisenox (Arsenic Trioxide)
0.25 mg/kg by vein over 2 hours, once a day for 7 days (Days -9 to -3).
Drug: Melphalan
100 mg/m2 by vein days -4,-3, over 30 minutes
Drug: Vitamin C (Ascorbic Acid)
Once a day through the vein for 7 days.
2: Active Comparator
Melphalan + Arsenic Trioxide + Vitamin C + Bortezomib (Level 1)
Drug: Trisenox (Arsenic Trioxide)
0.25 mg/kg by vein over 2 hours, once a day for 7 days (Days -9 to -3).
Drug: Velcade (Bortezomib)

Arm 1 (Level 1):

1.0 mg/m2 intravenous (IV) push on Days -9, -6, and -3. An IV push takes a short period of time (less than 1 minute).

Arm 2 (Level 2):

1.5 mg/m2 intravenous (IV) push on Days -9, -6, and -3. An IV push takes a short period of time (less than 1 minute).

Drug: Melphalan
100 mg/m2 by vein days -4,-3, over 30 minutes
Drug: Vitamin C (Ascorbic Acid)
Once a day through the vein for 7 days.
3: Active Comparator
Melphalan + Arsenic Trioxide + Vitamin C + Bortezomib (Level 2)
Drug: Trisenox (Arsenic Trioxide)
0.25 mg/kg by vein over 2 hours, once a day for 7 days (Days -9 to -3).
Drug: Velcade (Bortezomib)

Arm 1 (Level 1):

1.0 mg/m2 intravenous (IV) push on Days -9, -6, and -3. An IV push takes a short period of time (less than 1 minute).

Arm 2 (Level 2):

1.5 mg/m2 intravenous (IV) push on Days -9, -6, and -3. An IV push takes a short period of time (less than 1 minute).

Drug: Melphalan
100 mg/m2 by vein days -4,-3, over 30 minutes
Drug: Vitamin C (Ascorbic Acid)
Once a day through the vein for 7 days.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. a) Primary Refractory Disease (defined as failure to achieve even a partial response to induction therapy) b) Consolidation of a partial remission (defined as a decrease but continued presence of monoclonal protein on serum and urine immunofixation electrophoresis, and/or the presence of plasmacytosis on bone marrow aspirate and biopsy) c) Relapsing after prior therapy (disease relapsing after achieving a partial or complete response to prior conventional or high-dose therapy) .
  2. Age up to 75 years.
  3. Zubrod PS of <2.
  4. Left ventricular ejection fraction >40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
  5. FEV1, FVC and DLCO >40%. No symptomatic pulmonary disease.
  6. Serum bilirubin <2 X upper limit of normal, SGPT <4 X upper limit of normal. No evidence of chronic active hepatitis or cirrhosis. No effusion or ascites >1L prior to drainage.
  7. HIV-negative.
  8. Negative Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization
  9. Patient or guardian able to sign informed consent
  10. Corrected QT interval less than 470 msec.

Exclusion Criteria:

  1. Corrected QT interval greater than 470 msec.
  2. Patients in complete remission (defined as the absence of monoclonal protein on serum and urine immunofixation electrophoresis, and the absence of plasmacytosis in bone marrow aspirate and biopsy).
  3. Patients with non-secretory myeloma.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00469209

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Cephalon
Investigators
Principal Investigator: Muzaffar H. Qazilbash, MD U.T.M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UT MD Anderson Cancer Center ( Muzaffar H. Qazilbash, MD/Associate Professor )
Study ID Numbers: 2005-0893
Study First Received: May 3, 2007
Last Updated: October 22, 2009
ClinicalTrials.gov Identifier: NCT00469209     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Multiple Myeloma
Melphalan
Trisenox
Arsenic Trioxide
Ascorbic Acid
Vitamin C
Velcade
Bortezomib

Additional relevant MeSH terms:
Melphalan
Antioxidants
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Hemostatic Disorders
Hemorrhagic Disorders
Therapeutic Uses
Vitamins
Cardiovascular Diseases
Micronutrients
Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Hematologic Diseases
Growth Substances
Bortezomib
Vascular Diseases
Arsenic trioxide
Enzyme Inhibitors
Immunosuppressive Agents
Protective Agents
Pharmacologic Actions
Protease Inhibitors
Multiple Myeloma
Neoplasms

ClinicalTrials.gov processed this record on November 25, 2009