Bortezomib, Arsenic Trioxide, and Melphalan in Treating Patients Undergoing an Autologous Stem Cell Transplant For Multiple Myeloma

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Confirmed diagnosis of multiple myeloma (M-protein by serum protein electrophoresis or urine protein electrophoresis) and either bone marrow biopsy and aspirate demonstrating a plasma cell count > 10% or biopsy of a bone or soft tissue mass demonstrating a plasmacytoma

  • Demonstration of an indication for therapy based on symptoms (e.g., boney pain), hypercalcemia, anemia, renal insufficiency, symptomatic plasmacytomas, multiple boney lytic lesions, etc
  • Stable disease or has achieved a partial remission or complete remission to pre-transplant cyto-reductive therapy
  • Primary refractory disease (no response to therapy but stable) is permitted
• Candidate for high-dose chemotherapy with autologous stem cell transplantation based on stabilization of disease with preparative chemotherapy (regardless of the specific agents)
• A minimum of 2 x 10^6 CD34+ cells/kg must be collected prior to proceeding to transplant

Exclusion criteria:

• Evidence of active plasma cell leukemia
• Relapsed refractory disease (patients who have achieved at least a partial response [PR] to previous therapy and are now refractory [have not achieved a PR to subsequent therapy])
• Progressive disease on their last therapy

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 60-100%
• Creatinine < 3.0 mg/dL
• AST and ALT <2.5 times upper limit of normal
• Total bilirubin < 3 mg/dL
• WBC ≥ 2,000/mm³
• Platelet count ≥ 50,000/mm³
• If abnormal hematologic function is attributable to bone marrow infiltration by multiple myeloma, the principal investigator will decide on a case-by-case basis if the patient's bone marrow reserve is appropriate for this study
• Females of childbearing potential must have a negative serum pregnancy test prior to enrollment on the study and must use an effective barrier method while on the study
• Ejection fraction > 40% and no history of uncontrolled ischemic heart disease or congestive heart failure
• No evidence of cardiac amyloidosis by echocardiogram
• DLCO and FEV_1 ≥ 50%

Exclusion criteria:

• Active peripheral neuropathy ≥ grade 2
• Recurrent supraventricular arrhythmia or any type of sustained ventricular arrhythmia or conduction block (e.g., A-V block grade II or III, left bundle branch block)
• Known HIV infection
• Pregnant or lactating women
• Underlying medical condition that could be aggravated by the treatment or life-threatening disease unrelated to myeloma as evaluated by the enrolling physician
• History of second malignancy within the past 3 years and not in complete remission from that malignancy, excluding adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or local prostate cancer
• History of preexisting neurological disorders (grade 2 or higher by the NCI Common Toxicity Criteria, in particular seizure disorders)

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• Previous radiation therapy for palliation of cord compression or pathologic fractures is permitted provided last dose is given 14 days prior to initiation of chemotherapy

• Subjects with radiographic evidence of lytic bone disease receiving concomitant bisphosphonate therapy may be enrolled

  • Bisphosphonates should be held at least 1 week prior to the transplant but continuing bisphosphonates after day +60 is at the discretion of the treating physician

Exclusion criteria:

• Previous autologous or allogeneic transplantation
• Other investigational or experimental drug or therapy while on the study