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

Study Overview
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Brief Summary
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RATIONALE: Giving melphalan and bortezomib before and after a stem cell transplant stops the growth of abnormal cells by stopping them from dividing or killing them. Giving colony-stimulating factors and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy and monoclonal antibody therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. PURPOSE: This phase II trial is studying how well giving melphalan together with bortezomib followed by stem cell transplant works in treating patients with primary systemic amyloidosis.

Detailed Description
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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 to mobilize stem cells, which are then collected. Conditioning regimen: Patients receive bortezomib intravenously 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.

Official Title
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Phase II Trial of High-dose Melphalan and Bortezomib and Stem Cell Transplantation in Patients With AL Amyloidosis

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: filgrastim
* Drug: bortezomib
* Drug: melphalan
* Procedure: Stem Cell Infusion


Participation Criteria
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Eligibility Criteria
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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 plasma cell dyscrasia by serum/urine or bone marrow; or overwhelmingly convincing clinical features (e.g., macroglossia) associated with other systemic manifestations PATIENT CHARACTERISTICS: Southwest Oncology Group performance status 0-1 Fertile patients must use effective contraception Left ventricular ejection fraction ≥ 45% by Echocardiogram within the past 60 days diffusion capacity of lung for carbon monoxide ≥ 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Stem Cell Transplant with Bortezomib and Melphalan<br>Mobilization with Filgrastim Stem Cell Collection Bortezomib Melphalan Stem Cell infusion | Biological: filgrastim<br>* 16 mcg/kg daily beginning 3 days before stem cell collection through day before final stem cell collection<br>* Other names: Growth-Colony Stimulating Factor, neupogen;Drug: bortezomib<br>* 1.0 mg/m2/dose D -6, D-3, D +1, D + 4<br>* Other names: velcade;Drug: melphalan<br>* 100 mg/m2/dose D -2, D -1<br>* Other names: alkeran;Procedure: Stem Cell Infusion<br>* infusion of previously collected autologous stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Hematologic Response | complete and partial hematologic response defined as: Complete response: absence of detectable monoclonal protein in serum and urine, and bone marrow biopsy <5% plasma cells with no clonal predominance of kappa or lambda isotype. Partial response: any one of the following For patients with detectable and quantifiable marrow plasmacytosis, a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. For patients with a detectable monoclonal peak on serum protein electropheresis or urine protein electropheresis, a reduction in the peak height of 50% or more. For patients with quantifiable urinary kappa or lambda chain concentration, a reduction in daily light chain excretion (concentration x 24-hr urine volume). | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Surviving at 100 Days From Transplant |  | 100 Days from transplant date | 
| Number of Participants Surviving at 1 Year |  | one year from transplant | 
| Number of Participants Surviving at 2 Years |  | 2 years from transplant | 

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