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