Bortezomib, Cyclophosphamide, Dexamethasone, and Thalidomide in Treating Patients With Newly Diagnosed, Previously Untreated Multiple Myeloma

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma Read More

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma meeting 1 of the following criteria:

  • Monoclonal immunoglobulin spike on serum electrophoresis (IgG > 3.5 g/dL or IgA > 2.0 g/dL) and kappa or lambda light chain excretion > 1 g/day by 24-hour urine protein electrophoresis AND meets any of the following criteria:

    • Bone marrow plasmacytosis (10-30% plasma cells)
    • Lytic bone lesions

  • Monoclonal immunoglobulin of lesser magnitude present and bone marrow plasmacytosis (10-30% plasma cells) AND meets any of the following criteria:

    • Lytic bone lesions
    • IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

  • Bone marrow plasmacytosis (> 30% plasma cells) or plasmacytoma on tissue biopsy AND meets any of the following criteria:

    • Monoclonal immunoglobulin of lesser magnitude present
    • Lytic bone lesions
    • IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
  • FreeLite testing abnormal and kappa:lambda light chain ratio abnormal

• Symptomatic disease requiring treatment

  • Documented related organ or tissue involvement, if present

• Measurable disease, defined as 1 of the following:

  • Monoclonal immunoglobulin spike on serum electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/day
  • Abnormal FreeLite testing (for nonsecretors)

  • Patients with nonsecretory disease must meet either of the following criteria for measurability:

    • Has measurable protein by FreeLite testing
    • Untreated soft tissue plasmacytoma and/or evaluable disease in bone marrow
• Newly diagnosed, previously untreated disease
• No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes)
• No plasma cell leukemia

PATIENT CHARACTERISTICS:

• Karnofsky performance status 50-100%

• Platelet count ≥ 100,000/mm³ (≥ 50,000/mm³ if bone marrow is extensively infiltrated)

  • Extensive infiltration is defined as > 50% myeloma cells or plasma cells
• Hemoglobin ≥ 8.5 g/dL
• Absolute neutrophil count ≥ 1,500/mm³
• AST and ALT ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN (unless clearly related to the disease)
• Creatinine clearance ≥ 20 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 methods of effective contraception ≥ 4 weeks prior to beginning treatment, during, and for ≥ 4 weeks after completion of study treatment
• No impaired kidney function requiring dialysis
• No uncontrolled infection
• No HIV positivity
• No known active hepatitis B or C

• No cardiovascular disease including, but not limited to, any of the following:

  • Myocardial infarction within the past 6 months
  • New York Heart Association class II-IV heart failure
  • Uncontrolled angina
  • Severe uncontrolled ventricular arrhythmias
  • Clinically significant pericardial disease
  • Acute ischemic or active conduction system abnormalities by EKG
• No history of allergic reactions to compounds containing mannitol, bortezomib, or cyclophosphamide
• No second malignancy requiring concurrent treatment
• No other serious medical or psychiatric illness that would preclude study compliance
• No peripheral neuropathy ≥ grade 1

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, immunotherapy, vaccine therapy, therapeutic doses of steroids, or other agents for the treatment of active myeloma

  • Drugs given to prevent onset of myeloma allowed
  • Bisphosphonates for hypercalcemia or short course corticosteroids for hypercalcemia or cord compromise allowed
• Prior local radiotherapy with or without a brief exposure to steroids allowed

• More than 4 weeks since prior and no concurrent radiotherapy

  • Spot radiotherapy to ≤ 3 vertebrae allowed
• No concurrent steroids at > 10 mg of prednisone daily (or the equivalent) for other medical conditions (e.g., asthma, systemic lupus erythematosus, or rheumatoid arthritis)
• No other concurrent chemotherapy or investigational agents
• Concurrent daily acetylsalicylic acid required during course 4-6 of study treatment