Melphalan and Autologous Stem Cell Transplant Followed By Bortezomib and Dexamethasone in Treating Patients With Previously Untreated Systemic Amyloidosis

Study Overview
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Brief Summary
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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.

Official Title
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Risk-Adapted Intravenous Melphalan With Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients With Systemic Light-Chain (AL) Amyloidosis

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Drug: bortezomib
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Patients<br>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 | Drug: bortezomib<br>* Given IV<br>Drug: dexamethasone<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2-3 months post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary systemic amyloidosis