Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis
Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis
The drugs dexamethasone and bortezomib are both FDA-approved for the treatment of multiple
 myeloma, a disease very similar to amyloidosis. However, they are currently investigational
 for the treatment of amyloidosis.

 We want to find out if the addition of dexamethasone and bortezomib to standard high dose
 chemotherapy and stem cell transplant can help improve response.

 Standard treatment includes four steps: 1) Stem Cell Mobilization (standard) 2) Stem Cell
 Collection (standard) 3) Conditioning Regimen (Melphalan chemotherapy). The conditioning
 regimen helps to kill the abnormal cells in the body and makes room in the bone marrow for
 new blood stem cells to grow. 4) Stem Cell Infusion

 Participants in this study will have an additional treatment step called "induction therapy",
 designed as the first step towards reducing the number of abnormal cells in the body. Two
 cycles of the investigational drugs bortezomib and dexamethasone will be given during
 induction therapy. In addition, bortezomib will given as part of the conditioning regimen, in
 addition to the standard melphalan chemotherapy.
The drugs dexamethasone and bortezomib are both FDA-approved drugs for the treatment of
 multiple myeloma, a disease very similar to amyloidosis. However, they are currently
 investigational for the treatment of amyloidosis.

 The investigators want to find out if the addition of dexamethasone and bortezomib to
 standard treatment of high dose chemotherapy and stem cell transplant can help improve
 response to treatment.
Inclusion Criteria:

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

 1. Deposition of amyloid material by congo red stain showing characteristic green
 birefringence, and

 2. monoclonal light chain protein in the serum or urine or immunohistochemical
 studies or serum free light chain assay and

 3. evidence of tissue involvement other than carpal tunnel syndrome, i.e. positive
 immunohistochemical staining of bone marrow demonstrating clonal plasma cells; or
 tissue amyloid deposits with anti-kappa or anti-lambda anti-serum; evidence for a
 plasma cell dyscrasia (PCD) by serum/urine or bone marrow; or overwhelmingly
 convincing clinical features e.g. macroglossia, associated with other systemic
 manifestations.

 Note: 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.

 -  Must be at least 18 years of age.

 -  Must have a performance status of 0-2 by Southwest Oncology Group criteria

 -  Must have left ventricular ejection fraction (LVEF) at least 45% by echocardiogram
 within 60 days of enrollment

 -  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 less than 300 mg. Patients should not have
 received any cytotoxic therapy less than 4 weeks prior to registration and should have
 fully recovered from the effects of such therapy.

 -  Pulmonary Function Tests must show Diffusing capacity of the lungs for carbon monoxide
 (DLCO) at least 50%.

 -  Voluntary written informed consent before performance of any study-related procedure
 not part of normal medical care, with the understanding that consent may be withdrawn
 by the subject at any time without prejudice to future medical care.

 -  Female subject is either post-menopausal or surgically sterilized or willing to use an
 acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
 device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
 duration of the study.

 -  Male subject agrees to use an acceptable method for contraception for the duration of
 the study.

 Exclusion Criteria:

 -  No overt multiple myeloma (over 30% bone marrow plasmacytosis, extensive (great than
 2) lytic lesions, hypercalcemia).

 -  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 3 years.

 -  No known to be HIV positive.

 -  No platelet count of less than or equal to 70,000 within 14 days before enrollment.

 -  No absolute neutrophil count of less than or equal to 1000 within 14 days before
 enrollment.

 -  No greater than or equal to Grade 2 peripheral neuropathy within 14 days before
 enrollment.

 -  No myocardial infarction within 6 months prior to enrollment or has New York Heart
 Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled
 angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
 of acute ischemia or active conduction system abnormalities. Prior to study entry, any
 ECG abnormality at Screening has to be documented by the investigator as not medically
 relevant.

 -  No hypersensitivity to bortezomib, boron or mannitol.

 -  No pregnant or breast-feeding females. Confirmation that the subject is not pregnant
 must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG)
 pregnancy test result obtained during screening. Pregnancy testing is not required for
 post-menopausal or surgically sterilized women.

 -  Must not have received other investigational drugs with 14 days before enrollment

 -  No serious medical or psychiatric illness likely to interfere with participation in
 this clinical study.