Velcade, Trisenox, Vitamin C and Melphalan for Myeloma Patients - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Cephalon
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00469209

Purpose

Primary Objectives:

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
To evaluate the efficacy of a combination of bortezomib with arsenic trioxide, ascorbic acid and high-dose melphalan in patients with multiple myeloma
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:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Arsenic Cancer Multiple Myeloma Vitamin C

Drug Information available for: Ascorbic acid Bortezomib Melphalan Sarcolysin Arsenic trioxide Melphalan hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

Number of Patients Reaching Complete Response (CR) [ Time Frame: Baseline through Day 180, with assessments at Day 90 and Day 180 ] [ Designated as safety issue: Yes ]
Number of participants with CR at Day 180 who had maintained CR for at minimum of 4 weeks, and who had: No monoclonal protein in urine/serum when analyzed by immunofixation electrophoresis; bone marrow normal by morphological examination with <5% plasma cells, <1% aneuploid light chain restricted population by flow cytometry for DNA/cIg; and, while healing of bony lesion is not required, no new lytic lesion should appear. Further compression fracture of spine not considered progressive disease.

Secondary Outcome Measures:

Time to Toxicity [ Time Frame: Baseline to event occurence (assessed weekly first 30 days) ] [ Designated as safety issue: Yes ]
The time to patient toxicity of drug combination bortezomib with arsenic trioxide, ascorbic acid and high-dose melphalan defined in days from baseline measure to occurence of adverse events grade 4 (life threatening or disabling) according to National Cancer Institute Common Toxicity Criteria (CTC), version 3.

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
Active Comparator: No Bortezomib Arm 1: Melphalan 100 mg/m^2 intravenous (IV) days -4,-3 + Arsenic Trioxide 0.25 mg/kg IV for 7 days + Vitamin C IV daily	Drug: Trisenox (Arsenic Trioxide) 0.25 mg/kg by vein over 2 hours, once a day for 7 days (Days -9 to -3). Other Name: ATO Drug: Melphalan 100 mg/m2 by vein days -4,-3, over 30 minutes Other Name: Alkeran Drug: Vitamin C (Ascorbic Acid) 1000 mg once a day through the vein for 7 days.
Active Comparator: Bortezomib 1.0 mg/m^2 Arm 2: Bortezomib (Level 1) 1.0 mg/m^2 IV push on Days -9, -6, and -3, Melphalan 100 mg/m^2 IV days -4,-3 + Arsenic Trioxide 0.25 mg/kg IV for 7 days + Vitamin C IV daily	Drug: Trisenox (Arsenic Trioxide) 0.25 mg/kg by vein over 2 hours, once a day for 7 days (Days -9 to -3). Other Name: ATO Drug: Velcade (Bortezomib) Arm 1 (Level 1): 1.0 mg/m^2 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/m^2 intravenous (IV) push on Days -9, -6, and -3. An IV push takes a short period of time (less than 1 minute). Other Names: PDP-341 MLN341 PS-341 Drug: Melphalan 100 mg/m2 by vein days -4,-3, over 30 minutes Other Name: Alkeran Drug: Vitamin C (Ascorbic Acid) 1000 mg once a day through the vein for 7 days.
Active Comparator: Bortezomib 1.5 mg/m^2 Arm 3: Bortezomib (Level 2) 1.5 mg/m^2 IV push on Days -9, -6, and -3, Melphalan + Arsenic Trioxide 0.25 mg/kg IV for 7 days + Vitamin C IV daily	Drug: Trisenox (Arsenic Trioxide) 0.25 mg/kg by vein over 2 hours, once a day for 7 days (Days -9 to -3). Other Name: ATO Drug: Velcade (Bortezomib) Arm 1 (Level 1): 1.0 mg/m^2 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/m^2 intravenous (IV) push on Days -9, -6, and -3. An IV push takes a short period of time (less than 1 minute). Other Names: PDP-341 MLN341 PS-341 Drug: Melphalan 100 mg/m2 by vein days -4,-3, over 30 minutes Other Name: Alkeran Drug: Vitamin C (Ascorbic Acid) 1000 mg 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:

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).
Age up to 75 years.
Zubrod performance status of <2.
Left ventricular ejection fraction >40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
Forced expiratory volume (FEV1), forced volume vital capacity (FVC) and Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) >40%. No symptomatic pulmonary disease.
Serum bilirubin <2 times upper limit of normal, alanine aminotransferase/SGPT <4 times upper limit of normal. No evidence of chronic active hepatitis or cirrhosis. No effusion or ascites >1L prior to drainage.
HIV-negative.
Negative Beta human chorionic gonadotrophin (hCG) test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization
Patient or guardian able to sign informed consent
Corrected QT interval less than 470 msec.

Exclusion Criteria:

Corrected QT interval greater than 470 msec.
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).
Patients with non-secretory myeloma.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00469209

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Cephalon

Investigators

Principal Investigator:

Muzaffar H. Qazilbash, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Muzaffar H. Qazilbash, MD/Associate Professor, UT MD Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00469209 History of Changes
Other Study ID Numbers:	2005-0893
Study First Received:	May 3, 2007
Results First Received:	March 23, 2010
Last Updated:	June 13, 2011
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:

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
Ascorbic Acid

Vitamins
Melphalan
Arsenic trioxide
Bortezomib
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 12, 2012