S0115, High-Dose Melphalan and Autologous Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma or Primary Systemic Amyloidosis
S0115, High-Dose Melphalan and Autologous Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma or Primary Systemic Amyloidosis
RATIONALE: Drugs used in chemotherapy such as melphalan work in different ways to stop cancer
 cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral
 stem cell transplantation 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 giving melphalan together with autologous
 stem cell transplantation works in treating patients with multiple myeloma or primary
 systemic amyloidosis.
OBJECTIVES:

 -  Determine overall survival of patients with high-risk multiple myeloma, primary systemic
 amyloidosis, or light chain deposition disease treated with two courses of modified
 high-dose melphalan and autologous peripheral blood stem cell transplantation.

 -  Determine the hematologic response in patients treated with this regimen.

 -  Determine the qualitative and quantitative toxic effects of this regimen in these
 patients.

 -  Determine the prognostic significance of cytogenetic markers in these patients.

 OUTLINE: This is a multicenter study. Patients are stratified according to disease (high-risk
 multiple myeloma vs primary systemic amyloidosis vs both).

 -  Induction therapy (multiple myeloma patients only): Patients receive oral dexamethasone
 on days 1-4, 9-12, and 17-20 and oral thalidomide daily on days 1-35. Treatment repeats
 every 35 days for 2 courses in the absence of disease progression or unacceptable
 toxicity.

 -  Mobilization and stem cell collection:

 -  Multiple myeloma patients: Within 28-35 days after completion of induction therapy,
 patients receive cyclophosphamide IV over 2-3 hours on day 1 and filgrastim (G-CSF)
 subcutaneously (SC) daily beginning on day 2 and continuing through the day before
 the last leukapheresis. Usage of mesna IV on day 1 (prior to and twice after
 cyclophosphamide administration is recommended).

 -  Primary systemic amyloidosis patients: Patients receive G-CSF SC daily beginning on
 day 1 and continuing through the day before the last leukapheresis.

 All patients undergo leukapheresis for the collection of stem cells until the target number
 of CD34+ cells is reached.

 -  Conditioning regimen: Within 1-4 weeks after mobilization, patients receive modified
 high-dose melphalan IV over 20 minutes on day -2.

 -  Peripheral blood stem cell (PBSC) reinfusion: PBSCs are reinfused on day 0. Patients
 receive G-CSF SC daily beginning on day 1 and continuing until blood counts recover.

 Patients undergo a second autologous PBSC transplantation within 3-6 months, but no later
 than 12 months, after the first transplantation.

 -  Second conditioning regimen: Patients receive modified high-dose melphalan IV over 20
 minutes on day -2.

 -  Second PBSC infusion: PBSCs are infused on day 0.

 -  Maintenance regimen (multiple myeloma patients only): Between 4-8 weeks after the second
 transplantation, patients with no progressive disease receive oral dexamethasone once
 daily on days 1-4 and oral thalidomide once daily on days 1-28. Courses repeat every 28
 days for 2 years in the absence of disease progression or unacceptable toxicity.

 Patients are followed at 3 and 6 months and then annually thereafter.

 PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 20-25
 months.
DISEASE CHARACTERISTICS:

 -  At least 1 of the following diagnoses:

 -  Multiple myeloma

 -  Stage II or III disease

 -  At least 1 of the following must be present:

 -  Serum M-protein of IgG, IgA, IgD, IgE greater than 1.0 g/dL

 -  Urinary M-protein (Bence-Jones) at least 200 mg/24 hours

 -  No IgM peaks except in patients who have physiologic criteria to support a
 diagnosis of multiple myeloma (e.g., bony lesions, myeloma kidney-cast
 nephropathy, absence of adenopathy [unless pathology-proven to be plasma
 cell infiltration])

 -  No monoclonal gammopathy of undetermined significance

 -  No indolent or smoldering myeloma

 -  No disease progression on prior thalidomide or dexamethasone

 -  Histologically confirmed primary systemic amyloidosis

 -  No senile, secondary, localized, dialysis-related, or familial amyloidosis

 -  No severe cardiac involvement

 -  No pre-exertional syncope, ventricular arrhythmia, or symptomatic
 pleural effusions associated with cardiac involvement

 -  Light Chain Deposition Disease alone or in combination with multiple myeloma
 meeting the following criteria:

 -  Deposition of granular material containing free light chains/immunoglobulins
 that did not bind Congo red

 -  Evidence of plasma cell dyscrasia (i.e., monoclonal gammopathy in the serum
 or urine by immunofixation electrophoresis and/or clonal plasmacytosis) on
 bone marrow biopsy by immunohistochemistry and/or elevated serum-free light
 chain concentration

 -  Must have been diagnosed within the past year

 -  Concurrent enrollment in the myeloma repository protocol SWOG-S0309 must be offered

 PATIENT CHARACTERISTICS:

 Age

 -  18 and over (patients with amyloidosis only OR patients with amyloidosis and multiple
 myeloma OR patients with multiple myeloma only with poor renal function) OR

 -  70 and over (patients with multiple myeloma only with or without poor renal function)

 Performance status

 -  Zubrod 0-2

 Life expectancy

 -  Not specified

 Hematopoietic

 -  Absolute neutrophil count at least 1,000/mm^3

 -  Platelet count at least 100,000/mm^3

 Hepatic

 -  Bilirubin no greater than 2.5 times upper limit of normal (ULN)

 -  SGOT or SGPT no greater than 2.5 times ULN

 Renal

 -  No hemodialysis within 2 hours of melphalan or stem cell infusion

 Cardiovascular

 -  See Disease Characteristics

 -  Hemodynamically stable (i.e., systolic blood pressure > 90 mm Hg in a lying position
 within the past 42 days)

 -  No myocardial infarction within the past 6 months

 -  No congestive heart failure

 -  No arrhythmia refractory to medical therapy

 -  LVEF greater than 45% by echocardiogram or MUGA

 Pulmonary

 -  See Disease Characteristics

 -  No history of chronic obstructive or chronic restrictive pulmonary disease

 -  Pulmonary function studies (e.g., FEV_1 and FVC) at least 50% of predicted

 -  DLCO at least 50% of predicted

 -  Normal high resolution CT scan of the chest and acceptable arterial blood gases (i.e.,
 PO_2 greater than 70) required for patients unable to complete pulmonary function
 tests due to bone pain or fracture

 Other

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 -  Multiple myeloma patients receiving thalidomide must use 2 methods of effective
 contraception for at least 4 weeks before, during, and for at least 4 weeks after
 discontinuation of thalidomide

 -  HIV negative

 -  No other concurrent significant medical condition

 -  No concurrent uncontrolled life-threatening infection

 -  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

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  See Disease Characteristics

 Chemotherapy

 -  See Disease Characteristics

 -  Prior cumulative melphalan dose no more than 200 mg

 -  No other concurrent chemotherapy

 Endocrine therapy

 -  See Disease Characteristics

 -  No concurrent hormonal therapy

 Radiotherapy

 -  No concurrent radiotherapy

 Surgery

 -  Not specified

 Other

 -  Recovered from prior therapy

 -  Prior or concurrent bisphosphonates allowed