RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Ascorbic acid may help arsenic trioxide work better by making cancer cells more sensitive to the drug. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Giving arsenic trioxide and ascorbic acid together with bortezomib, thalidomide, and dexamethasone may stop the growth of and kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with ascorbic acid, bortezomib, thalidomide, and dexamethasone in treating patients with relapsed or refractory multiple myeloma or plasma cell leukemia.

OBJECTIVES:

Primary

• Determine the dose-limiting toxicity of arsenic trioxide when given in combination with ascorbic acid, bortezomib, thalidomide, and dexamethasone, particularly in terms of sensory neuropathy, in patients with relapsed or refractory multiple myeloma or plasma cell leukemia.

Secondary

• Determine the overall response rate, complete response rate, and response duration in patients treated with the maximum tolerated dose of this regimen.
• Determine whether the addition of arsenic trioxide and ascorbic acid to the treatment regimen (beginning in course 2) increases NFKB inhibition in these patients during courses 2 and 3 compared to course 1.

OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide.

• Induction therapy: Patients receive bortezomib IV over 3-5 seconds and dexamethasone IV or orally on days 1, 4, 8, and 11 and oral thalidomide once daily on days 1-21 (course 1). For course 2 and all subsequent courses, patients receive arsenic trioxide IV over 1-2 hours, ascorbic acid IV over 15 minutes, bortezomib IV over 3-5 seconds, and dexamethasone IV or orally on days 1, 4, 8, and 11 and thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a plateau in response proceed to maintenance therapy.
• Maintenance therapy: Patients receive oral dexamethasone every other day and oral thalidomide once daily in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

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