Trial of High Dose Melphalan/Stem Cell Transplant With or Without Bortezomib
Condition: AL Amyloidosis
MeSH terms: Immunoglobulin Light-chain Amyloidosis; Amyloidosis
Intervention: Bortezomib; Melphalan; Neupogen; Stem Cell Collection; Stem cell infusion
Intervention description: Conditioning Regimen:
Drug: Bortezomib: 1.0 mg/m2/dose D -6, D -3, D +1, D + 4 Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1; Conditioning Regimen:
Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1 Stem Cell Transplant: D 0; granulocyte colony-stimulating factor (G-CSF) mobilization 16mcg/kg x 4 days; collect at least 2.5 million cluster of differentiation 34 (CD34)+ stem cells; infusion of previously collected autologous stem cells
Intervention MeSH terms: Bortezomib; Melphalan; Lenograstim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: AL Amyloidosis; Stem Cell Transplantation

Summary:

      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.
    

Eligibility criteria:

        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.