Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma

NCT00153920 | Completed Phase 2 Results DMC

• 1 other identifier: 03-328
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 6

Brief Summary

Bortezomib (Velcade) has just recently been approved by the FDA for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. This study will determine if Velcade is effective in treating patients with multiple myeloma that have had no prior treatment for the disease. We will also use whole-genome scanning to identify drug response biomarkers in bone marrow samples as well as nerve fiber studies to compare nerves prior to the use of Velcade and after treatment with Velcade.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; Velcade; bortezomib

Outcome Measures

Primary Outcomes (1)

• Objective Response (OR) Rate

  Objective response was defined as complete response (CR) or partial response (PR) according to European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). CR required all of the following: Negative immunofixation on the serum and urine at two consecutive times for minimum 6 weeks; Disappearance of soft tissue plasmacytomas for at least 6 weeks; \<5% plasma cells in bone marrow on 2 determinations for a minimum of 6 weeks; No increase in the size or number of lytic bone lesions. PR required all the following: ≥50% reduction in the level of the serum monoclonal protein on 2 determinations for minimum 6 weeks; If present, reduction in 24-hour urinary light chain excretion either by ≥90% or to \<200 mg on 2 determinations for minimum 6 weeks; ≥50% reduction size of soft tissue plasmacytomas for minimum 6 weeks; No increase in the number or size of lytic bone lesions. Development of a compression fracture does not exclude response in either category.

  Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Secondary Outcomes (5)

• Very Good Partial Response (VGPR) Rate

  Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

• Time to Progression (TTP)

  Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months.

• Progression-Free Survival (PFS)

  Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months as of the data analysis.

• Number of Participants With Treatment-Emergent Sensory Neuropathy

  Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

• Number of Participants With Treatment-Emergent Neuropathic Pain

  Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Study Arms (1)

bortezomib

EXPERIMENTAL

Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.

Drug: bortezomib

Interventions

bortezomib DRUG

Also known as: Velcade

bortezomib

Eligibility Criteria

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

You may qualify if:

• Diagnosis of multiple myeloma based upon standard criteria
• Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of \> 1 g/dl and/or urine monoclonal immunoglobulin spike of \> 200mg/24 hours.
• Karnofsky performance status of \> 60
• Hemoglobin \> 8.0 g/dL
• AST (SGOT) \< 3 x ULN
• ALT \< 3 x ULN
• Total bilirubin \< 2 x ULN
• Is infertile or is practicing an adequate form of contraception
• years of age or older

You may not qualify if:

• Prior treatment with systemic chemotherapy
• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes
• Plasma cell leukemia
• Calculated or measured creatinine clearance \< 30 mL/minute within 14 days of enrollment
• Grade 2 or greater peripheral neuropathy
• Hypersensitivity to bortezomib, boron or mannitol
• Severe hypercalcemia
• HIV positive
• Known active hepatitis B or C
• New York Hospital Association Class III or IV heart failure
• Second malignancy requiring concurrent treatment
• Other serious medical or psychiatric illness
• Pregnant women
• Dialysis dependent patients

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Beth Israel Deaconess Medical Center: collaborator
• Massachusetts General Hospital: collaborator
• Brigham and Women's Hospital: collaborator
• Roswell Park Cancer Institute: collaborator
• Emory University: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (6)

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 04263, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Publications (1)

• Richardson PG, Xie W, Mitsiades C, Chanan-Khan AA, Lonial S, Hassoun H, Avigan DE, Oaklander AL, Kuter DJ, Wen PY, Kesari S, Briemberg HR, Schlossman RL, Munshi NC, Heffner LT, Doss D, Esseltine DL, Weller E, Anderson KC, Amato AA. Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol. 2009 Jul 20;27(21):3518-25. doi: 10.1200/JCO.2008.18.3087. Epub 2009 Jun 15.

  PMID: 19528374 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Paul G. Richardson
• Organization: Dana-Farber Cancer Institute

Paul_Richardson@dfci.harvard.edu

617.632.2104

Study Officials

• Paul Richardson, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: December 1, 2003
• Primary Completion: July 1, 2007
• Study Completion: September 1, 2008
• Last Updated: June 11, 2019
• Results First Posted: February 18, 2016

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)