Doxorubicin Hydrochloride Liposome, Melphalan, and Bortezomib in Treating Patients With Relapsed or Refractory Stage I, Stage II, or Stage III Multiple Myeloma

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma

  • Stage I, II, or III disease according to Durie-Salmon staging criteria

• Progressive disease, defined as one of the following:

  • For secretory disease:

    • A 25% increase in serum M-protein or Bence Jones protein (an absolute increase of 0.5 g/dL serum M-protein or ≥ 200 mg/24 hours of urine light chain excretion)

  • For nonsecretory disease:

    • Bone marrow biopsy with > 25% increase in plasma cells or an absolute increase of ≥ 10% over prior known level
    • Development of new or worsening existing lytic bone lesions or soft tissue plasmacytomas
    • Hypercalcemia (i.e., calcium > 11.5 mg/dL)
    • Relapsed after complete response

• Must have received ≥ 2 of the following therapeutic regimens for multiple myeloma:

  • Nonmyeloablative transplantation

    • No significant graft-versus-host disease
    • At least 30 days since prior immunosuppressive therapy (concurrent prednisone allowed provided dose is ≤ 10 mg daily)
  • Mobilization with chemotherapy followed by either single or tandem autologous stem cell transplantation (considered 1 prior regimen)
  • Mobilization with chemotherapy followed by autologous and subsequent nonmyeloablative allogeneic stem cell transplantation (considered 1 prior regimen)
  • Any combination of drugs given concurrently (considered 1 prior regimen)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• Absolute neutrophil count > 1,000/mm^3 (no colony-stimulating factors)
• Platelet count > 50,000/mm^3 (no transfusion support)
• Bilirubin ≤ 2.0 mg/dL
• AST ≤ 4 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
• No history of allergic reaction to compounds containing boron or mannitol
• No active uncontrolled viral (including HIV), bacterial, or fungal infection
• No motor or sensory neuropathy ≥ grade 2
• No myocardial infarction within the past 6 months
• No New York Heart Association class III or IV heart failure
• No uncontrolled angina
• No severe uncontrolled arrhythmia
• No acute ischemia by EKG
• LVEF ≥ 35% by MUGA (MUGA required in patients whose lifetime cumulative doxorubicin hydrochloride dose > 400 mg/m^2)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No grade III or IV toxicity due to previous antineoplastic therapy (except alopecia)
• At least 3 weeks since prior chemotherapy
• No prior doxorubicin HCl liposome, melphalan, and bortezomib as combination therapy (single or two-drug combinations of these are allowed)
• No concurrent corticosteroids (≤ 10 mg prednisone/day or equivalent allowed)
• No other concurrent chemotherapy
• No concurrent thalidomide
• No other concurrent investigational therapy
• No other concurrent antineoplastic treatment for multiple myeloma, including clarithromycin
• No concurrent radiation therapy
• No concurrent nonsteroidal anti-inflammatory agents