RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vitamin C may increase the effectiveness of arsenic trioxide by making cancer cells more sensitive to the drug.

PURPOSE: Phase I/II trial to determine the effectiveness of arsenic trioxide plus vitamin C in treating patients who have recurrent or refractory multiple myeloma.

OBJECTIVES:

• Determine the maximum tolerated dose of arsenic trioxide when administered with ascorbic acid in patients with recurrent or refractory multiple myeloma.
• Determine the therapeutic efficacy of this treatment combination in these patients.
• Determine the expression of MDR and Bcl-xL genes and the intracellular levels of GSH in these patients before and after this treatment regimen and assess whether these measures have prognostic value.

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

• Phase I: Patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over 5-10 minutes on days 1-5 weekly for 5 weeks. Treatment continues every 7 weeks for up to 6 courses 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 reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive the MTD of arsenic trioxide with ascorbic acid as outlined above.

Patients are followed monthly for up to 5 years.

PROJECTED ACCRUAL: A total of 31-43 patients (6-18 for phase I and 16-25 for phase II) will be accrued for this study within 2.5 years.

• Dietary Supplement: ascorbic acid
• Drug: arsenic trioxide

DISEASE CHARACTERISTICS:

• Histologically confirmed multiple myeloma

  • M-protein by serum protein electrophoresis or urine protein electrophoresis
  • Quantitative determination of immunoglobulin
  • Bone marrow biopsy and aspirate with a plasma cell count greater than 10%

  • Refractory or chemoresistant disease defined as failure to respond (less than 50% reduction in M protein level) or progression within 2 months after receiving at least 2 chemotherapy regimens including:

    • Alkylating based regimen (melphalan) in combination with steroids (prednisone) or other chemotherapy regimens (e.g., vincristine, bleomycin, melphalan, cyclophosphamide, and prednisone or vincristine, carmustine, doxorubicin, and prednisone)
    • Vincristine, doxorubicin, and dexamethasone (VAD) regimen
    • Pulse therapy with high dose steroids alone
    • High dose alkylating agent and autologous stem cell transplantation
    • Allogeneic bone marrow transplantation

  • Plateau phase defined as M protein in the serum or urine for more than 6 weeks despite response to prior therapy

    • Must have received at least 2 of the chemotherapy regimens listed above or equivalent regimens

  • Recurrent disease defined as progression more than 2 months after initial therapy and failure to respond (less than 50% reduction or progression in M protein levels) to 1 chemotherapy regimen listed above or other salvage regimens (e.g., high-dose cyclophosphamide or topotecan)

    • Must have received VAD or other equivalent chemotherapy regimen
    • Should be considered for autologous or allogenic transplantation
    • Prior local radiotherapy allowed

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,000/mm^3*
• Platelet count at least 50,000/mm^3* NOTE: *Unless attributable to bone marrow infiltration by multiple myeloma

Hepatic:

• Bilirubin less than 3 mg/dL
• Transaminases less than 2.5 times upper limit of normal (ULN)

Renal:

• Creatinine less than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No cardiac arrhythmias including recurrent supraventricular arrhythmia, any type of sustained ventricular arrhythmia, or conduction block (atrioventricular block grade II or III, left bundle branch block)
• Ejection fraction at least 30%
• No uncontrolled ischemic heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 4 months after study
• HIV negative
• No grade 3 or higher neurological disorder, including seizure disorders
• No underlying medical condition that would preclude study
• No other active malignancy except adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics
• At least 2 weeks since prior chemotherapy

Endocrine therapy:

• See Disease Characteristics
• Concurrent steroid treatment allowed except for primary treatment of myeloma

Radiotherapy:

• See Disease Characteristics
• Concurrent local radiotherapy for pain or symptom control allowed provided the pain or symptom is not related to disease progression

Surgery:

• Not specified

Other:

• No other concurrent ascorbic acid supplements
• No other concurrent investigational drug or therapy
• Concurrent bisphosphonates allowed