Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
primary systemic amyloidosis
Brief summary
The purpose of this study in patients needing treatment for AL amyloidosis is to see how well treatment with IV melphalan works and then, if some clonal plasma cells are still present about 2 to 3 months after melphalan treatment, to see how well treatment with bortezomib and dexamethasone works to reduce the rest of the clonal plasma cell disease.
Interventions
DRUGbortezomib
Given IV
DRUGdexamethasone
Given orally
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed amyloidosis * Diagnosed within the past 12 months * Clonal plasma cell disorder, as demonstrated by any of the following: * Presence of M-protein in serum and/or urine by immunofixation and/or serum free light chain assay * Clonal population of plasma cells in the bone marrow based on kappa/lambda staining of a marrow biopsy * Negative genetic testing for hereditary forms of amyloidosis * No amyloid-specific syndrome (e.g., carpal tunnel syndrome or skin purpura) as the only evidence of disease * Vascular amyloidosis only in a bone marrow biopsy specimen or in plasmacytoma is not indicative of systemic amyloidosis * No advanced cardiac amyloidosis * Must have symptomatic involvement of no more than 2 of the following visceral organ systems: * Kidneys * Liver/gastrointestinal * Peripheral/autonomic nervous system * Heart * No persistent pleural effusions * No clinically overt multiple myeloma with \> 30% plasma cells in the bone marrow or lytic bone lesions * Able to undergo autologous stem cell transplantation PATIENT CHARACTERISTICS: * SWOG performance status 0-3 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Bilirubin \< 2.0 mg/dL * Creatinine clearance \< 51 mL/min allowed * LVEF \> 45% by echocardiogram * No New York Heart Association class III-IV congestive heart failure * No history of cardiac syncope * No recurrent symptomatic arrhythmias * No oxygen-dependent restrictive cardiomyopathy * No myocardial infarction within the past 6 months * Pulmonary diffusion capacity \> 50% predicted by pulmonary function testing * No uncontrolled infection * No other active malignancy, except for any of the following: * Adequately treated basal cell or squamous cell skin cancer * In situ cervical cancer * Adequately treated stage I cancer from which the patient is currently in complete remission * Any other cancer from which the patient has been disease-free for 5 years * No hypersensitivity to bortezomib, boron, or mannitol * No HIV positivity * No serious medical or psychiatric illness that would preclude study compliance PRIOR CONCURRENT THERAPY: * At least 14 days since prior investigational drugs * No prior therapy for monoclonal plasma disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic and Organ Response | 2-3 months post transplant | patients will be assessed for hematologic response (the response of the clonal plasma cell disease). If the plasma cell disease persists, then they will receive 6 cycles of adjuvant therapy with bortezomib and dexamethasone; patients with peripheral neuropathy will receive dexamethasone alone because of the risk of neuropathy associated with bortezomib. Symptomatic organ involvement with amyloid as defined below. Patients must have symptomatic involvement of no more than 2 of the following 4 visceral organ-systems: kidneys, liver/GI, peripheral/autonomic nervous system, and heart. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients All patients treated with Melphalan with Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients with Systemic Light-Chain (AL) Amyloidosis | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 57 years |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 20 / 40 |
Outcome results
Primary
Hematologic and Organ Response
patients will be assessed for hematologic response (the response of the clonal plasma cell disease). If the plasma cell disease persists, then they will receive 6 cycles of adjuvant therapy with bortezomib and dexamethasone; patients with peripheral neuropathy will receive dexamethasone alone because of the risk of neuropathy associated with bortezomib. Symptomatic organ involvement with amyloid as defined below. Patients must have symptomatic involvement of no more than 2 of the following 4 visceral organ-systems: kidneys, liver/GI, peripheral/autonomic nervous system, and heart.
Time frame: 2-3 months post transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Hematologic and Organ Response | Complete Hematologic Response | 11 participants |
| All Patients | Hematologic and Organ Response | Partial Response | 7 participants |
| All Patients | Hematologic and Organ Response | Stable Disease | 18 participants |