Trial of High Dose Melphalan/Stem Cell Transplant With or Without Bortezomib
Trial of High Dose Melphalan/Stem Cell Transplant With or Without Bortezomib
Standard treatment for AL Amyloidosis is high-dose melphalan and stem cell transplant.

 This study will compare the safety and effectiveness of standard treatment with high-dose
 melphalan and stem cell transplant, compared with investigational bortezomib when used in
 combination with standard treatment with high-dose melphalan and stem cell transplant for AL
 amyloidosis.
This study seeks to enroll patients with AL amyloidosis who have been recommended for
 standard treatment with high-dose melphalan and stem cell transplant.

 Standard treatment for this disease is high-dose melphalan and stem cell transplant.

 The purpose of this study is to compare the safety and effectiveness of standard treatment
 with high-dose melphalan and stem cell transplant, compared with investigational bortezomib
 when used in combination with standard treatment with high-dose melphalan and stem cell
 transplant for AL amyloidosis.

 Patients enrolled in this study will receive either standard treatment with high-dose
 melphalan and stem cell transplant, or investigational bortezomib used in combination with
 standard treatment with high-dose melphalan and stem cell transplant.
Inclusion Criteria:

 1. Histological diagnosis of primary systemic (AL) amyloidosis based on:

 -  Deposition of amyloid material by Congo red stain showing characteristic apple
 green birefringence,AND…

 -  evidence of a clonal plasma cell dyscrasia with monoclonal protein in the serum
 or urine by immunofixation electrophoresis studies AND/OR abnormal serum free
 light chain assay AND/OR clonal plasma cells in the bone marrow exam demonstrated
 by immunohistochemistry, flow cytometry or in situ hybridization AND…

 -  evidence of organ involvement other than carpal tunnel syndrome. Patients with
 senile, secondary, localized, dialysis-related or familial amyloidosis are not
 eligible. Confirmation of tissue diagnosis at all sites of organ dysfunction is
 encouraged, but not required.

 2. Patients must be > 18 years of age.

 3. Patients must have a performance status of 0-2 by Eastern Cooperative Oncology Group
 (ECOG) criteria

 4. Patients must have left ventricular ejection fraction (LVEF) > 45% by echocardiogram
 within 60 days of enrollment

 5. Pulmonary Function Tests must show diffusing capacity of lung for carbon monoxide
 (DLCO) > 50%.

 6. All patients must be informed of the investigational nature of this study and must
 sign and give written informed consent in accordance with institutional and federal
 guidelines.

 Exclusion Criteria:

 1. Patients with recent (< 6 months) myocardial infarction, congestive heart failure, New
 York Heart Association (NYHA) class III/IV or arrhythmia which are refractory to
 medical therapy are ineligible.

 2. Prior chemotherapy with alkylating agent allowed only if no evidence of
 Myelodysplastic Dysplastic Syndrome (MDS) morphologically or cytogenetically. Total
 cumulative dose of oral melphalan must be < 300 mg. Patients should not have received
 any cytotoxic therapy < 4 weeks prior to registration and should have fully recovered
 from the effects of such therapy.

 3. Patients must not have overt multiple myeloma (>30% bone marrow plasmacytosis and,
 extensive (>2) lytic lesions and hypercalcemia).

 4. No other prior malignancy is allowed except for the following: adequately treated
 basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
 Stage I or II cancer from which the patient is currently in complete remission, or any
 other cancer from which the patient has been disease-free for 5 years.

 5. Patients must not be HIV positive.

 6. Pregnant or nursing women may not participate. Women and men of reproductive potential
 may not participate unless they have agreed to use an effective contraceptive method.