S0115, High-Dose Melphalan and Autologous Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma or Primary Systemic Amyloidosis
Condition: Multiple Myeloma; Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis; Amyloidosis
Intervention: filgrastim; cyclophosphamide; dexamethasone; melphalan; thalidomide; peripheral blood stem cell transplantation
Intervention MeSH terms: Thalidomide; Dexamethasone; Cyclophosphamide; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: primary systemic amyloidosis; stage II multiple myeloma; stage III multiple myeloma

Summary:

      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.
    

Eligibility criteria:

        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