Arsenic Trioxide and Ascorbic Acid Combined With Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma or Plasma Cell Leukemia

DISEASE CHARACTERISTICS:

• Histologically confirmed multiple myeloma (MM) or plasma cell leukemia meeting 1 of the following criteria:

  • Relapsed or refractory disease after treatment with prior effective therapy
  • Exhibited < a partial response to the last therapy

• Measurable disease, defined by 1 of the following:

  • Serum M protein ≥ 1.0 g/dL
  • Urine M-protein ≥ 500 mg/24 hours
  • Plasmacytoma with bidimensional measurements on CT scan or MRI (each axis ≥ 1 cm)
• Previously treated with ≥ 1 induction chemotherapy regimen for MM
• No known CNS involvement by multiple myeloma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod or SWOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC ≥ 1,500/mm^3
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 80,000/mm^3
• Hemoglobin ≥ 8.5 g/dL

• No history of heparin-induced thrombocytopenia

  • Low blood counts allowed if marrow is heavily infiltrated by multiple myeloma

Hepatic

• Bilirubin ≤ 1.5 times upper limit normal (ULN)
• AST and ALT ≤ 2.5 times ULN

Renal

• Creatinine ≤ 2.5 mg/dL

Cardiovascular

• QTc < 480 msec on EKG in the presence of serum potassium ≥ 4.0 mEq/dL and serum magnesium ≥ 1.8 mg/dL
• LVEF ≥ 55% by ECHO or MUGA
• No prior deep vein thrombosis, unless on concurrent anticoagulation
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No history of ventricular arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• No history of allergic reactions or severe adverse reactions attributed to compounds of similar chemical or biological composition to study drugs
• No other malignancy in the past 2 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No peripheral neuropathy ≥ grade 2
• No ongoing or active infection requiring IV antibiotics
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• Controlled HIV disease allowed as long as there are no associated comorbid complications
• No active peptic ulcer disease
• No other condition that would confer a high risk of bleeding complications

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior thalidomide or lenalidomide for MM
• Prior autologous or allogeneic stem cell transplant for MM allowed
• Concurrent hematopoietic growth factors (e.g., epoetin alfa, filgrastim [G-CSF]) for MM allowed

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior arsenic trioxide for MM

Endocrine therapy

• More than 4 weeks since prior corticosteroids for MM

Radiotherapy

• More than 4 weeks since prior therapeutic radiotherapy (e.g., to plasmacytomas)

  • Palliative radiotherapy for painful symptomatic lytic skeletal lesions allowed within the past 4 weeks

Surgery

• Not specified

Other

• More than 4 weeks since prior cytotoxic agents or other therapy (e.g., bortezomib) for MM
• More than 30 days (or 5 half-lives) since prior investigational agents
• Concurrent bisphosphonates for MM allowed
• No other concurrent anticancer therapy
• No other concurrent investigational agents