Chemotherapy Plus Peripheral Stem Cell Transplant in Treating Patients Who Have Multiple Myeloma or Primary Systemic Amyloidosis

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: This phase II trial is studying how well chemotherapy and peripheral stem cell transplant work in treating patients with multiple myeloma or primary systemic amyloidosis.

Detailed Description
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OBJECTIVES: Determine the response rate in patients with multiple myeloma or primary systemic amyloidosis treated with high-dose chemotherapy with autologous hematopoietic stem cell support. Determine the toxicity of this regimen in these patients. Determine the disease-free survival and overall survival of patients with multiple myeloma treated with this regimen. OUTLINE: Patients are stratified according to disease response to prior treatment (responsive vs refractory or relapsed) and diagnosis (multiple myeloma vs primary systemic amyloidosis). Following a course of induction chemotherapy, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until the completion of peripheral blood stem cell (PBSC) harvesting. Patient who do not mobilize sufficient cells undergo bone marrow harvest. Patients receive melphalan IV over 30 minutes on days -2 and -1. Half of the stored PBSCs and/or bone marrow is reinfused on day 0. Patients receive sargramostim (GM-CSF) daily beginning on day 0 and continuing until blood counts recover. Patients with primary systemic amyloidosis who are not responding to or are unable to tolerate treatment do not proceed to the second course of therapy. Within 4-6 weeks after receiving melphalan, patients receive oral busulfan on days -8 to -5 followed by cyclophosphamide IV continuously on days -4 and -3. The remaining half of PBSCs and/or bone marrow is reinfused on day 0. Patients receive GM-CSF daily beginning on day 0 and continuing until blood counts recover. Within 4-12 weeks after receiving the second course of high-dose chemotherapy, multiple myeloma patients receive maintenance therapy consisting of interferon alfa SC 3 days a week, after blood counts recover. Patients are followed every 3 months for 1 year and then annually for 5 years. PROJECTED ACCRUAL: Approximately 60-75 patients (25 for responsive disease stratum, 25 for refractory or relapsed disease stratum, and 10-25 for primary systemic amyloidosis stratum) will be accrued for this study within 3 years.

Official Title
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Phase 2 Study Of High Dose Chemotherapy Followed By Autologous Hematopoietic Stem Cell Support In Patients With Multiple Myeloma And Primary Light Chain Amyloidosis

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: filgrastim
* Biological: recombinant interferon alfa
* Biological: sargramostim
* Drug: busulfan
* Drug: cyclophosphamide
* Drug: melphalan
* Procedure: autologous bone marrow transplantation
* Procedure: bone marrow ablation with stem cell support
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed multiple myeloma OR Primary systemic amyloidosis resulting in significant organ dysfunction and decreased quality of life Complete or partial response after standard chemotherapy Primary refractory or relapsed multiple myeloma after first-line treatment with standard chemotherapy Ineligible for higher priority national or institutional clinical studies PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 2 times normal Renal: Creatinine less than 2.5 mg/dL or on stable hemodialysis Cardiovascular: LVEF at least 45% Pulmonary: DLCO at least 60% of predicted OR Approval by pulmonologist Other: HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: Concurrent participation in gene therapy trials allowed Chemotherapy: See Disease Characteristics No other concurrent chemotherapy Endocrine therapy: No concurrent steroids as antiemetics during chemotherapy No concurrent anticancer hormonal therapy Radiotherapy: Not specified Surgery: Not specified Other: No concurrent barbiturates or acetaminophen during chemotherapy Concurrent participation in supportive care trials allowed

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Biological: recombinant interferon alfa|nan|
|Biological: sargramostim|nan|
|Drug: busulfan|nan|
|Drug: cyclophosphamide|nan|
|Drug: melphalan|nan|
|Procedure: autologous bone marrow transplantation|nan|
|Procedure: bone marrow ablation with stem cell support|nan|
|Procedure: peripheral blood stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival at 2 years (patients with responsive disease) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hematologic toxicity |  |  | 
| Time to an absolute neutrophil count |  |  | 
| Platelet independence |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, primary systemic amyloidosis