A Phase II Trial With VELCADE® (PS-341), Cytoxan (Cyclophosphamide), Dexamethasone and Thalomid® (VEL-CTD) in Previously Untreated Multiple Myeloma Patients

Inclusion Criteria

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