Multiple Myeloma
Conditions
Keywords
stage II multiple myeloma, stage III multiple myeloma
Brief summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving bortezomib together with thalidomide may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with thalidomide works in treating patients with newly diagnosed stage II or stage III multiple myeloma.
Detailed description
OBJECTIVES: * Determine the antitumor efficacy of bortezomib and thalidomide in patients with newly diagnosed stage II or III multiple myeloma. * Determine the incidence and severity of peripheral motor/sensory neuropathy in patients treated with this regimen. * Assess the ability to mobilize and collect stem cells in patients who undergo future autologous peripheral stem cell transplantation. * Determine the time to response in patients treated with this regimen. * Assess the quality of life of patients treated with this regimen. OUTLINE: This is an open-label study. Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral thalidomide once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses. Patients who plan to undergo transplantation AND achieve ≥ 50% reduction in the tumor burden proceed to transplantation off study. Patients who do not undergo transplantation receive 2 additional courses of therapy beyond best response for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response after completion of treatment may receive maintenance therapy comprising bortezomib IV every 2 months and oral thalidomide\* once daily OR twice every 2 months (i.e., the day before and the day of bortezomib administration) in the absence of disease progression or unacceptable toxicity. NOTE: \*For patients who had previously discontinued thalidomide, maintenance therapy may consist of bortezomib only. Quality of life is assessed at baseline, at the beginning of each study course, and after completion of study treatment. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Interventions
DRUGbortezomib
DRUGthalidomide
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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
DISEASE CHARACTERISTICS: * Newly diagnosed Salmon-Durie stage II or III multiple myeloma * Untreated disease OR patient underwent prior therapy for this cancer that lasted no more than 2 weeks * Measurable paraprotein in serum or urine (serum free-lite assay measurement allowed) * No evidence of cord compression requiring concurrent steroids PATIENT CHARACTERISTICS: * Creatinine clearance ≥ 30 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use 2 methods of contraception, including ≥ 1 highly effective method, 4 weeks before, during, and for ≥ 4 weeks after completion of study treatment * No known HIV positivity * No peripheral neuropathy ≥ grade 2 * No hypersensitivity to bortezomib, boron, or mannitol PRIOR CONCURRENT THERAPY: * No prior bortezomib * More than 28 days since prior regimens with a duration of \> 1 week but ≤ 2 weeks * No steroids within 14 days prior to study entry * No concurrent corticosteroids except for the treatment of a nonmalignant condition * May not exceed the equivalent dose of prednisone 10 mg/day * No concurrent chemotherapy, immunotherapy, radiotherapy, or surgery * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response to Treatment | 1-6 months | Clinical evaluations of disease response were determined with each cycle. Bone marrow biopsies were done at baseline and at study termination. Clinical responses were defined by the International Myeloma Working Group criteria: Stringent Complete Response (SCR), CR and normal free light chain ratio and no clonal cells in bone marrow; Complete Response (CR), Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; Very Good Partial Response (VGPR), Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; Partial Response (PR), ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. Objective response is defined as a best overall response of SCR, CR, VGPR, or PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral Motor and Sensory Neuropathy (Grade 2 and Higher) | 1-6 months | Neuropathy was monitored using Total Neuropathy Score reduced (TNSr). |
| Mobilization of Stem Cells in Patients Proceeding to Autologous Peripheral Stem Transplantation | 1-6 months | — |
| The Time to Response | 1-6 months | — |
| Quality of Life | 0-6 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib and Thalidomide The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide.
bortezomib
thalidomide | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Bortezomib and Thalidomide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 30 |
| serious Total, serious adverse events | 10 / 30 |
Outcome results
Primary
Clinical Response to Treatment
Clinical evaluations of disease response were determined with each cycle. Bone marrow biopsies were done at baseline and at study termination. Clinical responses were defined by the International Myeloma Working Group criteria: Stringent Complete Response (SCR), CR and normal free light chain ratio and no clonal cells in bone marrow; Complete Response (CR), Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; Very Good Partial Response (VGPR), Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; Partial Response (PR), ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. Objective response is defined as a best overall response of SCR, CR, VGPR, or PR.
Time frame: 1-6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bortezomib and Thalidomide | Clinical Response to Treatment | 81.5 percentage of participants |
Secondary
Mobilization of Stem Cells in Patients Proceeding to Autologous Peripheral Stem Transplantation
Time frame: 1-6 months
Population: Analysis not completed as the information was not relevant since no patients went on to transplant.
Secondary
Peripheral Motor and Sensory Neuropathy (Grade 2 and Higher)
Neuropathy was monitored using Total Neuropathy Score reduced (TNSr).
Time frame: 1-6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bortezomib and Thalidomide | Peripheral Motor and Sensory Neuropathy (Grade 2 and Higher) | 19 participants |
Secondary
Quality of Life
Time frame: 0-6 months
Population: Analysis not done on subject population.
Secondary
The Time to Response
Time frame: 1-6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib and Thalidomide | The Time to Response | 2 months |