RATIONALE: Drugs used in chemotherapy, such as fluphenazine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I/II trial is studying the side effects and best dose of fluphenazine and to see how well it works in treating patients with refractory advanced multiple myeloma.

OBJECTIVES:

• Determine the safety of high-dose fluphenazine hydrochloride in patients with refractory advanced multiple myeloma.
• Determine the pharmacological properties of this drug.
• Determine the effectiveness of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive high-dose fluphenazine hydrochloride IV 3 times on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of patients receive escalating doses of fluphenazine hydrochloride until the maximum tolerated dose is determined.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed multiple myeloma

  • Advanced disease
  • Must be refractory to ≥ 2 different methods of standard treatment

• Measurable disease, defined as serum paraprotein ≥ 1g/L or urine light chain ≥ 200 mg/24 hours

• No brain involvement or leptomeningeal disease

• No spinal cord compression unless the following criteria are met:

  • Patient has undergone prior surgery or radiotherapy
  • Neurological findings are ≤ grade 1
  • Patient is off steroids for spinal cord edema or is on a stable regimen of ≤ 10 mg/day of prednisone or equivalent

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 (ECOG PS 3 allowed if related to skeletal lesions)
• Life expectancy ≥ 12 weeks
• Absolute granulocyte count ≥ 1,000/mm^3*
• Platelet count ≥ 50,000/mm^3*
• Hemoglobin ≥ 8.0 g/dL* (no transfusion within the past 7 days)
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 2 times ULN
• Creatinine clearance ≥ 30 mL/min
• LVEF ≥ 40%
• QTc < 450 msec
• No evidence of dysrhythmias on EKG
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No congestive heart failure
• No angina pectoris
• No cardiac arrhythmia
• No uncontrolled hypertension, defined as systolic blood pressure (BP) > 180 mm Hg and/or diastolic BP > 105 mm Hg
• No myocardial infarction within the past year
• No active infection
• No HIV, hepatitis B, or hepatitis C infection
• No history of psychosis
• No history of subcortical brain damage
• No hypersensitivity to fluphenazine hydrochloride or other phenothiazines
• No history of seizures or extrapyramidal symptoms
• No other serious illness or medical condition
• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix NOTE: *Patients with values outside of this range due to infiltration by myeloma may be allowed at the discretion of the investigator

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior therapy

• At least 21 days since prior chemotherapy, immunotherapy, or radiotherapy

• At least 21 days since prior and no concurrent systemic steroids

  • Patients who have been taking chronically administered steroids for ≥ 1 month at a dose ≤ 10 mg/day of prednisone or equivalent are eligible

• At least 28 days since prior investigational agents

• At least 6 weeks since prior selective serotonin reuptake inhibitors (SSRIs) (a wash-out period equivalent to 5 times the terminal elimination half-life is required for tricyclic antidepressants or norepinephrine reuptake inhibitors)

• No concurrent SSRIs, tricyclic antidepressants, or norepinephrine reuptake inhibitors

• No concurrent dialysis therapy

• No concurrent hematopoietic growth factors except epoetin alfa

  • Treatment with hematopoietic growth factors may be started during study if patient develops or has progressive cytopenia

• No concurrent anticholinergics or other antipsychotics

• No concurrent antiseizure drugs except Neurontin for treatment of neuropathy