Phase II Study of Melphalan, Arsenic Trioxide, and Ascorbic Acid in Patients With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of multiple myeloma meeting at least 1 of the following criteria:

- Relapsed disease after a response to standard first-line chemotherapy (e.g.,
vincristine, doxorubicin, and dexamethasone [VAD] OR melphalan and prednisone) or
first-line high-dose chemotherapy

- Refractory disease (failed to achieve at least stable disease) to most recent
chemotherapy with or without systemic corticosteroids

- Measurable disease, defined as a monoclonal immunoglobulin spike on serum
electrophoresis of ≥ 1 g/dL AND/OR urine monoclonal immunoglobulin spike of ≥ 200
mg/24 hours

- No non-secretory myeloma

- No plasma cell leukemia

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- More than 3 months

Hematopoietic

- Platelet count ≥ 50,000/mm^3 (30,000/mm^3 if bone marrow is extensively infiltrated)

- Hemoglobin ≥ 8.0 g/dL

- Absolute neutrophil count ≥ 1,000/mm^3

- Pancytopenia secondary to multiple myeloma or hypersplenism allowed

Hepatic

- AST and ALT ≤ 3 times upper limit of normal (ULN)

- Bilirubin ≤ 2 times ULN (unless clearly related to disease)

- No known active hepatitis B or C infection

Renal

- Calcium < 14 mg/dL

Cardiovascular

- No evidence of acute ischemia or new conduction system abnormality by
electrocardiogram

- No myocardial infarction within the past 6 months

- No New York Heart Association class III or IV heart failure

- No poorly controlled hypertension

- No prolonged corrected QT interval (> 460 ms) with potassium > 4 mmol/L and magnesium
≥ 1.8 mmol/L

Other

- No active infection

- No POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes)

- No diabetes mellitus

- No other serious medical or psychiatric illness that would preclude study
participation

- No known allergic reaction attributable to compounds of similar chemical or
biological composition to study drugs

- No history of grand mal seizures

- HIV negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 4 weeks since prior immunotherapy or antibody therapy

Chemotherapy

- See Disease Characteristics

- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

Endocrine therapy

- See Disease Characteristics

- No other concurrent corticosteroids

Radiotherapy

- More than 4 weeks since prior radiotherapy

Surgery

- More than 4 weeks since prior major surgery

Other

- No other concurrent investigational agents