Back to resultsBortezomib (Velcade) in Patients With Untreated Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma, Velcade, bortezomib
Eligibility Criteria
Inclusion Criteria: 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 18 years of age or older Exclusion Criteria: 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
Sites / Locations
- Emory Winship Cancer Institute
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- Dana-Farber Cancer Institute
- Roswell Park Cancer Institute
- Memorial Sloan-Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
bortezomib
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Very Good Partial Response (VGPR) Rate
Very good partial response or better was defined per International Uniform Response criteria (Durie B, Harousseau JL, Miquel JS, et al Leukemia 2006). See CR requirements in primary outcome measure plus if serum and urine M protein were unmeasurable then immunoglobulin free light chain (FLC) must be in a normal ratio of 0.26-1.65 at two consecutive times. VGPR required the following: Serum and urine M-component detectable by immunofixation but not on electrophoresis; >=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP); if the serum and urine M protein were unmeasurable then a >90% decrease in the difference between involved and uninvolved FLC levels.
Time to Progression (TTP)
TTP based on the Kaplan-Meier method is defined as the time from start of treatment to documentation of disease progression (PD). Participants without evidence of PD were censored at the latest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing or new soft tissue plasmacytomas and/or lytic lesions; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).
Progression-Free Survival (PFS)
PFS based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the earliest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing soft tissue plasmacytomas and/or lytic lesions or new; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).
Number of Participants With Treatment-Emergent Sensory Neuropathy
Number of participants experiencing any grade treatment-emergent sensory neuropathy events based on CTCAEv3 as reported on case report forms.
Number of Participants With Treatment-Emergent Neuropathic Pain
Number of participants experiencing any grade treatment-emergent neuropathic pain events based on CTCAEv3 as reported on case report forms.
Full Information
NCT ID
NCT00153920
First Posted
September 8, 2005
Last Updated
May 30, 2019
Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Brigham and Women's Hospital, Roswell Park Cancer Institute, Emory University, Memorial Sloan Kettering Cancer Center, Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00153920
Brief Title
Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma
Official Title
Phase II Trial of Velcade (Bortezomib) in Patients With Previously Untreated Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
September 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Brigham and Women's Hospital, Roswell Park Cancer Institute, Emory University, Memorial Sloan Kettering Cancer Center, Millennium Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
Primary Objective
• To evaluate the objective response rate (CR + PR) to bortezomib alone in patients with newly diagnosed multiple myeloma.
Secondary Objectives
To evaluate the tolerability and toxicity.
To evaluate time to progression.
To assess the frequency and severity of peripheral neuropathy.
To evaluate the impact of early intervention with dose modification and explore symptomatic treatment of peripheral neuropathy.
Exploratory Objectives
• To perform pharmacogenomic analysis of molecular markers associated with response or non-response.
Statistical Design A one stage design is used to evaluate ORR. With 60 evaluable participants, if at least 27 objective responses are observed then bortezomib will be considered promising. The probability of concluding the treatment promising is >0.95 with a true ORR of 55% and <0.07 with a true ORR of 35%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
multiple myeloma, Velcade, bortezomib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bortezomib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
Velcade
Primary Outcome Measure Information:
Title
Objective Response (OR) Rate
Description
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.
Time Frame
Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).
Secondary Outcome Measure Information:
Title
Very Good Partial Response (VGPR) Rate
Description
Very good partial response or better was defined per International Uniform Response criteria (Durie B, Harousseau JL, Miquel JS, et al Leukemia 2006). See CR requirements in primary outcome measure plus if serum and urine M protein were unmeasurable then immunoglobulin free light chain (FLC) must be in a normal ratio of 0.26-1.65 at two consecutive times. VGPR required the following: Serum and urine M-component detectable by immunofixation but not on electrophoresis; >=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP); if the serum and urine M protein were unmeasurable then a >90% decrease in the difference between involved and uninvolved FLC levels.
Time Frame
Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).
Title
Time to Progression (TTP)
Description
TTP based on the Kaplan-Meier method is defined as the time from start of treatment to documentation of disease progression (PD). Participants without evidence of PD were censored at the latest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing or new soft tissue plasmacytomas and/or lytic lesions; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).
Time Frame
Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months.
Title
Progression-Free Survival (PFS)
Description
PFS based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the earliest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing soft tissue plasmacytomas and/or lytic lesions or new; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).
Time Frame
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.
Title
Number of Participants With Treatment-Emergent Sensory Neuropathy
Description
Number of participants experiencing any grade treatment-emergent sensory neuropathy events based on CTCAEv3 as reported on case report forms.
Time Frame
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).
Title
Number of Participants With Treatment-Emergent Neuropathic Pain
Description
Number of participants experiencing any grade treatment-emergent neuropathic pain events based on CTCAEv3 as reported on case report forms.
Time Frame
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
18 years of age or older
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Richardson, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
04263
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19528374
Citation
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.
Results Reference
result
Learn more about this trial
Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma
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