fluphenazine in treating patients with refractory advanced multiple myeloma

Conditions: Multiple Myeloma and Plasma Cell Neoplasm

Summary: 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.

Eligibility criteria:
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

Keywords: stage iii multiple myeloma refractory multiple myeloma stage ii multiple myeloma