Multiple Myeloma
Conditions
Keywords
previously treated multiple myeloma
Brief summary
Patients will receive Bortezomib, Dexamethasone, and Doxorubicin in 21 day cycles a total of 4 to 8 times (based on response to the treatment). Patients will also receive acetyl-L-carnitine (ALCAR) daily.
Detailed description
The primary objective of this study is to assess overall response rate to the treatment. Secondary objectives include: evaluating and describing the incidence of chemotherapy-induced peripheral neuropathy using the FACT/GOG-Ntx assessment tool; evaluating the utility of adding ALCAR to the chemotherapy to reduce the incidence of peripheral neuropathy; and evaluating the utility of the Grooved Pegboard Completion Time as a longitudinal measure of peripheral neuropathy.
Interventions
DRUGBort, Dex, and Dox with ALCAR
Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
Sponsors
Millennium Pharmaceuticals, Inc.
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with previously treated multiple myeloma with measurable serum or urine monoclonal protein.
Exclusion criteria
* Patients with previous doxorubicin treatment totaling 220 mg/m2 or more * LVEF less than 45% * Patients with \>grade II sensory neuropathy at baseline as assessed by the PI will be excluded * No history of seizures as ALCAR may lower the seizure threshold * Known HIV infection * Current pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bortezomib, Dexamethasone, Doxorubicin, and ALCAR | Every 21 days, up to 24 weeks | Anti-tumor responses were analyzed descriptively and summarized in tabular format. Ninety percent confidence intervals for the percentage of subjects with a confirmed anti-tumor response were constructed using the method proposed by Duffy-Santner. Complete response defined as: no evidence of M-protein on immunofixation of serum and/or urine AND less than 5% plasma cells in the bone marrow biopsy. Partial response defined as: 50 to 99% decrease in M-protein on serum and/or urine protein electrophoresis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From date of randomization until the date of death from any cause, assessed up to 7 years | — |
| Progression-free Survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 years. | Progression is defined as any of the following: 1) 25% or greater increase in M-protein as measured by serum or urine protein electrophoresis. There must be an absolute minimum increase of 0.5 g/dl in serum M spike or 0.2 gram of specific urinary light chains to constitute progression, 2) 25% or greater increase in the percentage or plasma cells in the bone marrow biopsy, or 3) new bone lesions or an increase in the size of old lesions on x-ray. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from University of Wisconsin Hospital and Clinics and the Wisconsin Oncology Network between April 2004 and September 2010.
Pre-assignment details
No events between enrollment and group assignment. All subjects are enrolled are assigned to the same group.
Participants by arm
| Arm | Count |
|---|---|
| Bort, Dex, and Dox With ALCAR Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 1 |
| Overall Study | Disease Progression | 10 |
| Overall Study | Other Complicating Disease | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Started Non-Protocol Therapy | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Bort, Dex, and Dox With ALCAR |
|---|---|
| Age, Customized 30-39 | 1 participants |
| Age, Customized 40-49 | 4 participants |
| Age, Customized 50-59 | 6 participants |
| Age, Customized 60-69 | 12 participants |
| Age, Customized 70-79 | 7 participants |
| Age, Customized 80-89 | 2 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 10 / 32 |
Outcome results
Primary
Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bortezomib, Dexamethasone, Doxorubicin, and ALCAR
Anti-tumor responses were analyzed descriptively and summarized in tabular format. Ninety percent confidence intervals for the percentage of subjects with a confirmed anti-tumor response were constructed using the method proposed by Duffy-Santner. Complete response defined as: no evidence of M-protein on immunofixation of serum and/or urine AND less than 5% plasma cells in the bone marrow biopsy. Partial response defined as: 50 to 99% decrease in M-protein on serum and/or urine protein electrophoresis.
Time frame: Every 21 days, up to 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bort, Dex, and Dox With ALCAR | Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bortezomib, Dexamethasone, Doxorubicin, and ALCAR | 53 percentage of participants |
Secondary
Overall Survival
Time frame: From date of randomization until the date of death from any cause, assessed up to 7 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bort, Dex, and Dox With ALCAR | Overall Survival | 28.3 months |
Secondary
Progression-free Survival
Progression is defined as any of the following: 1) 25% or greater increase in M-protein as measured by serum or urine protein electrophoresis. There must be an absolute minimum increase of 0.5 g/dl in serum M spike or 0.2 gram of specific urinary light chains to constitute progression, 2) 25% or greater increase in the percentage or plasma cells in the bone marrow biopsy, or 3) new bone lesions or an increase in the size of old lesions on x-ray.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bort, Dex, and Dox With ALCAR | Progression-free Survival | 5 months |