Melphalan, Bortezomib, and Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

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 (G-CSF)
to mobilize stem cells, which are then collected.

- Conditioning regimen: Patients receive bortezomib IV 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.

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 PCD by serum/urine or bone marrow; or overwhelmingly convincing clinical
features (e.g., macroglossia) associated with other systemic manifestations

PATIENT CHARACTERISTICS:

- SWOG performance status 0-1

- Fertile patients must use effective contraception

- LVEF ≥ 45% by ECHO within the past 60 days

- DLCO ≥ 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