Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
stage II multiple myeloma, stage III multiple myeloma
Brief summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving bortezomib as maintenance therapy after autologous stem cell transplantation may kill more cancer cells and prolong remission. PURPOSE: This phase I/II trial is studying the side effects and best dose of adjuvant bortezomib as maintenance therapy and to see how well it works in treating patients who have undergone stem cell transplantation for intermediate or advanced multiple myeloma.
Detailed description
OBJECTIVES: * Determine response rate, as defined by resolution of bone marrow plasmacytosis and monoclonal paraproteinemia, in the first year after autologous peripheral blood stem cell transplantation in patients with intermediate or advanced multiple myeloma treated with adjuvant bortezomib. * Compare progression-free survival of patients treated with adjuvant bortezomib with historical controls treated with autologous transplantation alone. * Determine the toxicity of this drug in these patients (phase I). OUTLINE: This is a multicenter, dose-escalation study. Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2 years.
Interventions
DRUGbortezomib
Sponsors
Millennium Pharmaceuticals, Inc.
Jonsson Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of intermediate or advanced multiple myeloma meeting criteria for at least 1 2 following: * Intermediate- to high-M-component production rates (immunoglobulin \[Ig\]G \> 5 g/dL or immunoglobulin A (IgA) \> 3 g/dL or urine M component \> 4 g/24 hours) * More than one osteolytic bone lesion or radiographic evidence of diffuse osteoporosis * β-2 microglobulin \> 3 * Nonsecretory myeloma if bone marrow plasmacytosis is greater than 30% * Must have undergone autologous peripheral blood stem cell transplantation within the past 3-4 months * Age 18 to 69 years old * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 30,000/mm\^3 * serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) ≤ 300 IU * Bilirubin ≤ 2 mg/dL * Creatinine ≤ 2.0 mg/dL * Creatinine clearance ≥ 30 mL/min * Negative pregnancy test * Fertile patients must use effective contraception
Exclusion criteria
* concurrent major cardiac disease that would preclude study participation * concurrent major pulmonary disease that would preclude study participation * pregnant or nursing * peripheral neuropathy ≥ grade 2 * history of hypersensitivity to bortezomib, boron, or mannitol * concurrent major gastrointestinal or bladder disease that would preclude study participation * concurrent major neurologic or psychiatric disease that would preclude study participation * dementia or significantly altered mental status that would preclude giving informed consent * prior interferon post-transplantation * prior thalidomide post-transplantation * prior chemotherapy post-transplantation * prior radiotherapy post-transplantation * prior investigational therapy post-transplantation * prior bortezomib * prior therapy for myeloma post-transplantation * other concurrent anti-myeloma therapy * other concurrent investigational therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | signed consent to progression or end of trial. Up to 5 years. | Disease Progression: The day when bone marrow recurrence and/or new lytic bone marrow lesions on radiograph and/or progressive M-component paraprotein (\ 25% increase) were detected. Paraprotein progression will be confirmed labs on the consecutive month. |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival | up to 5 years from time of consent |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib bortezomib administration beginning 3-4 month after the day of transplantation after resolution of bone marrow transplant toxicities | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
| Overall Study | Relapsed | 8 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Bortezomib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 30 |
| serious Total, serious adverse events | 2 / 30 |
Outcome results
Primary
Progression-free Survival
Disease Progression: The day when bone marrow recurrence and/or new lytic bone marrow lesions on radiograph and/or progressive M-component paraprotein (\ 25% increase) were detected. Paraprotein progression will be confirmed labs on the consecutive month.
Time frame: signed consent to progression or end of trial. Up to 5 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib | Progression-free Survival | 29 months |
Secondary
Overall Survival
Time frame: up to 5 years from time of consent
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib | Overall Survival | 55 months |