Fluphenazine in Treating Patients With Refractory Advanced Multiple Myeloma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I/IIa, Open-Label, Dose-Escalation Study to Determine the Safety, Tolerance, and Preliminary Activity of Intravenous High-Dose Fluphenazine HCI in Patients With Advanced Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Drug: fluphenazine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluphenazine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  |  | 
| Efficacy |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III multiple myeloma, refractory multiple myeloma, stage II multiple myeloma