Tandem Autologous Stem Cell Transplantation in Treating Patients With Primary Systemic (AL) Amyloidosis

Study Overview
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Brief Summary
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RATIONALE: Autologous stem cell transplantation may be effective treatment for primary systemic (AL) amyloidosis. PURPOSE: This phase II trial is studying how well tandem (two) autologous stem cell transplantation works in treating patients with primary systemic (AL) amyloidosis.

Detailed Description
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OBJECTIVES: Determine the tolerability of tandem autologous stem cell transplantation in patients with AL amyloidosis. Determine whether this regimen can convert a hematologic non-complete response (CR) to CR in these patients. Determine the overall survival of patients treated with this regimen. OUTLINE: First transplantation: Patients receive filgrastim (G-CSF) subcutaneously once daily beginning 3 days before the initiation of stem cell collection and continuing until the day before the completion of stem cell collection. Patients may undergo bone marrow harvest if an inadequate number of peripheral blood stem cells are collected. Patients receive high-dose melphalan IV over 20 minutes on days -3 and -2. Patients undergo autologous stem cell transplantation (ASCT) on day 0. Second transplantation: Within 6-12 months after the first ASCT, patients not achieving a complete response receive high-dose melphalan IV over 20 minutes on days -3 and -2 and a second ASCT on day 0. Treatment continues in the absence of unacceptable toxicity. Patients are followed at 3 and 6 months, 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study within 2-3 years.

Official Title
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A Phase II Trial of Tandem Transplantation in AL Amyloidosis

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: filgrastim
* Drug: melphalan
* Procedure: autologous peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DISEASE CHARACTERISTICS: Histologically confirmed AL amyloidosis, meeting 1 of the following criteria: Plasma cell dyscrasia, evidenced by 1 of the following: Monoclonal protein in the serum or urine by immunofixation electrophoresis Plasmacytosis of the bone marrow with monoclonal staining for kappa or lambda light chain isotype Macroglossia with at least 1 other site having biopsy proven amyloidosis and absence of a mutant transthyretin is ruled out PATIENT CHARACTERISTICS: Age 18 to 65 Performance status SWOG 0-2 Life expectancy At least 1 year Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular LVEF ≥ 45% by MUGA or echocardiogram Pulmonary DLCO ≥ 50% Other Not pregnant or nursing Fertile patients must use effective contraception Able to tolerate 2 courses of high-dose therapy HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Prior alkylating agent chemotherapy allowed provided there is no morphologic or cytogenetic evidence of myelodysplastic syndromes Prior total cumulative oral melphalan dose < 300 mg Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other At least 4 weeks since prior cytotoxic therapy and recovered Exclusion Criteria: No senile, secondary, localized, dialysis-related, or familial amyloidosis No overt multiple myeloma (e.g., greater than 30% bone marrow plasmacytosis, extensive [more than 2] lytic lesions, hypercalcemia) Cardiovascular No myocardial infarction within the past 6 months No congestive heart failure No arrhythmia refractory to therapy No evidence of symptomatic transient ischemic attacks or strokes No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

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 |
| --- | --- |
| Other: tandem transplant<br>Drug: filgrastim 16 mg/kg/day for 3 days prior to stem cell collection, through day before last collection Drug: melphalan 200 mg/kg over 2 days Procedure/Surgery: autologous peripheral blood stem cell transplantation autologous peripheral blood stem cell transplantation | Drug: filgrastim<br>* 16 mg/kg/day for 3 days prior to stem cell collection, through day before last collection<br>Drug: melphalan<br>* 200 mg/kg over 2 days<br>* Other names: alkeran;Procedure: autologous peripheral blood stem cell transplantation<br>* autologous peripheral blood stem cell transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety |  | 100 days, 6 months, and annual | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy |  | one year | 

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