Velcade, Trisenox, Vitamin C and Melphalan for Myeloma Patients

NCT00469209 | Completed Phase 1 Results DMC

• 1 other identifier: 2005-0893
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives:

1. 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. 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. 3.To determine the effects of bortezomib on melphalan pharmacokinetics

Conditions

Myeloma

Keywords

Multiple Myeloma; Melphalan; Trisenox; Arsenic Trioxide; Ascorbic Acid; Vitamin C; Velcade; Bortezomib

Outcome Measures

Primary Outcomes (1)

• Number of Patients Reaching Complete Response (CR)

  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.

  Baseline through Day 180, with assessments at Day 90 and Day 180

Secondary Outcomes (1)

• Time to Toxicity

  Baseline to event occurence (assessed weekly first 30 days)

Study Arms (3)

No Bortezomib

ACTIVE COMPARATOR

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); Drug: Melphalan; Drug: Vitamin C (Ascorbic Acid)

Bortezomib 1.0 mg/m^2

ACTIVE COMPARATOR

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); Drug: Velcade (Bortezomib); Drug: Melphalan; Drug: Vitamin C (Ascorbic Acid)

Bortezomib 1.5 mg/m^2

ACTIVE COMPARATOR

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); Drug: Velcade (Bortezomib); Drug: Melphalan; Drug: Vitamin C (Ascorbic Acid)

Interventions

Trisenox (Arsenic Trioxide) DRUG

0.25 mg/kg by vein over 2 hours, once a day for 7 days (Days -9 to -3).

Also known as: ATO

Bortezomib 1.0 mg/m^2; Bortezomib 1.5 mg/m^2; No Bortezomib

Velcade (Bortezomib) DRUG

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).

Also known as: PDP-341, MLN341, PS-341

Bortezomib 1.0 mg/m^2; Bortezomib 1.5 mg/m^2

Melphalan DRUG

100 mg/m2 by vein days -4,-3, over 30 minutes

Also known as: Alkeran

Bortezomib 1.0 mg/m^2; Bortezomib 1.5 mg/m^2; No Bortezomib

Vitamin C (Ascorbic Acid) DRUG

1000 mg once a day through the vein for 7 days.

Bortezomib 1.0 mg/m^2; Bortezomib 1.5 mg/m^2; No Bortezomib

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Cephalon: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Multiple Myeloma

Interventions

Arsenic Trioxide; Bortezomib; Melphalan; Ascorbic Acid

Condition Hierarchy (Ancestors)

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; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Muzaffar H. Qazilbash, MD/Professor, Stem Cell Transplantation
• Organization: University of Texas M.D. Anderson Cancer Center

mqazilba@mdanderson.org

713-745-3458

Study Officials

• Muzaffar H. Qazilbash, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 3, 2007
• First Posted: May 4, 2007
• Study Start: June 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: September 24, 2020
• Results First Posted: April 25, 2011

Record last verified: 2020-09

Locations

US (1)