Multiple Myeloma
Conditions
Keywords
primary systemic amyloidosis
Brief summary
RATIONALE: Giving melphalan and bortezomib before and after a stem cell transplant stops the growth of abnormal cells by stopping them from dividing or killing them. Giving colony-stimulating factors and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy and monoclonal antibody therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. PURPOSE: This phase II trial is studying how well giving melphalan together with bortezomib followed by stem cell transplant works in treating patients with primary systemic amyloidosis.
Detailed description
OBJECTIVES: * To determine if hematologic responses to high-dose melphalan and autologous stem cell transplantation increase with addition of bortezomib in the conditioning regimen in patients with primary systemic amyloidosis. OUTLINE: * Autologous stem cell mobilization and collection: Patients receive filgrastim to mobilize stem cells, which are then collected. * Conditioning regimen: Patients receive bortezomib intravenously on days -6, -3, 1, and 4 and oral high-dose melphalan on days -2 and -1. * Stem cell transplantation: Patients undergo autologous stem cell transplantation on day 0. After completion of study therapy, patients are followed every 6 months for 1 year and annually thereafter.
Interventions
BIOLOGICALfilgrastim
16 mcg/kg daily beginning 3 days before stem cell collection through day before final stem cell collection
DRUGbortezomib
1.0 mg/m2/dose D -6, D-3, D +1, D + 4
DRUGmelphalan
100 mg/m2/dose D -2, D -1
PROCEDUREStem Cell Infusion
infusion of previously collected autologous stem cells
Sponsors
Boston Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed primary systemic amyloidosis based on the following criteria: * Amyloid light-chain disease * Deposition of amyloid material by congo red stain showing characteristic green birefringence * Monoclonal light chain protein (Bence Jones protein) in the serum or urine, immunohistochemical studies, or serum free light chain assay * Evidence of tissue involvement other than carpal tunnel syndrome (i.e., positive immunohistochemical staining of bone marrow demonstrating clonal plasma cells); tissue amyloid deposits with anti-kappa or anti-lambda anti-serum; evidence for a plasma cell dyscrasia by serum/urine or bone marrow; or overwhelmingly convincing clinical features (e.g., macroglossia) associated with other systemic manifestations PATIENT CHARACTERISTICS: * Southwest Oncology Group performance status 0-1 * Fertile patients must use effective contraception * Left ventricular ejection fraction ≥ 45% by Echocardiogram within the past 60 days * diffusion capacity of lung for carbon monoxide ≥ 50% PRIOR CONCURRENT THERAPY: * Prior chemotherapy with alkylating agent allowed provided there is no morphological or cytogenetic evidence of myelodysplastic syndromes * Prior total cumulative dose of oral melphalan \< 300 mg * At least 4 weeks since prior cytotoxic therapy and fully recovered
Exclusion criteria
* No senile, secondary, localized, dialysis-related, or familial amyloidosis * No overt multiple myeloma (\> 30% of bone marrow plasmacytosis, extensive \[\> 2\] lytic lesions, or hypercalcemia) * Not pregnant or nursing * No myocardial infarction within the past 6 months, congestive heart failure, or arrhythmia refractory to therapy * No prior malignancy except for any of the following: * Adequately treated basal cell or squamous cell skin cancer * In situ cervical cancer * Adequately treated stage I or II cancer currently in complete remission * Any cancer from which the patient has been disease-free ≥ 5 years * No advanced (grade 3-4) pre-existing neuropathy * No HIV positivity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hematologic Response | one year | complete and partial hematologic response defined as: Complete response: absence of detectable monoclonal protein in serum and urine, and bone marrow biopsy \<5% plasma cells with no clonal predominance of kappa or lambda isotype. Partial response: any one of the following 1. For patients with detectable and quantifiable marrow plasmacytosis, a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. 2. For patients with a detectable monoclonal peak on serum protein electropheresis or urine protein electropheresis, a reduction in the peak height of 50% or more. 3. For patients with quantifiable urinary kappa or lambda chain concentration, a reduction in daily light chain excretion (concentration x 24-hr urine volume). |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Surviving at 100 Days From Transplant | 100 Days from transplant date |
| Number of Participants Surviving at 1 Year | one year from transplant |
| Number of Participants Surviving at 2 Years | 2 years from transplant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCT With Bortezomib and Melphalan Mobilization with Filgrastim Stem Cell Collection (SCC) Bortezomib Melphalan Stem Cell infusion
filgrastim: 16 mcg/kg daily beginning 3 days before SCC through day before final SCC
bortezomib: 1.0 mg/m2/dose D -6, D-3, D +1, D + 4
melphalan: 100 mg/m2/dose D -2, D -1
Stem Cell Infusion: infusion of previously collected autologous stem cells | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | SCT With Bortezomib and Melphalan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Gender Female | 5 Participants |
| Gender Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 9 / 9 |
Outcome results
Primary
Number of Participants With Hematologic Response
complete and partial hematologic response defined as: Complete response: absence of detectable monoclonal protein in serum and urine, and bone marrow biopsy \<5% plasma cells with no clonal predominance of kappa or lambda isotype. Partial response: any one of the following 1. For patients with detectable and quantifiable marrow plasmacytosis, a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. 2. For patients with a detectable monoclonal peak on serum protein electropheresis or urine protein electropheresis, a reduction in the peak height of 50% or more. 3. For patients with quantifiable urinary kappa or lambda chain concentration, a reduction in daily light chain excretion (concentration x 24-hr urine volume).
Time frame: one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplant With Bortezomib and Melphalan | Number of Participants With Hematologic Response | 6 participants |
Secondary
Number of Participants Surviving at 100 Days From Transplant
Time frame: 100 Days from transplant date
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplant With Bortezomib and Melphalan | Number of Participants Surviving at 100 Days From Transplant | 9 participants |
Secondary
Number of Participants Surviving at 1 Year
Time frame: one year from transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplant With Bortezomib and Melphalan | Number of Participants Surviving at 1 Year | 9 participants |
Secondary
Number of Participants Surviving at 2 Years
Time frame: 2 years from transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stem Cell Transplant With Bortezomib and Melphalan | Number of Participants Surviving at 2 Years | 9 Participants |