Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of multiple myeloma that is relapsed or relapsed-and-refractory after at least 2 or more prior lines of therapy. Patients must have achieved at least minor response (MR) to at least one prior line of therapy
• Progressive disease must have occurred either during or subsequent to the patient's last treatment for multiple myeloma prior to the current enrollment
• Measurable disease defined by serum M-protein ≥1 g/dL, or urine light chain ≥200 mg/24 hours, or abnormal serum FLC ratio with involved FLC > 10 mg/dL provided serum FLC ratio is abnormal
• Age >18 years
• Eastern Cooperative Oncology Group (performance status of ≤20
• Life expectancy ≥12 weeks
• Signed written informed consent per institutional and federal regulatory requirements
• Did not receive chemotherapy (including systemic steroids), immunotherapy (interferon), Imids (thalidomide/lenalidomide), proteasome inhibitors (bortezomib), or radiotherapy for at least 21 days prior to Day 1 of Cycle 1
• Did not receive any investigational treatment for at least 28 days prior to study entry
• Absolute granulocyte count of ≥1,000/μL, platelet count ≥50,000/μL, and hemoglobin ≥8.0 g/dL, with no transfusion within the preceding 7 days
• Adequate liver function defined by a bilirubin value ≤2 times the upper limit of normal (ULN), and transaminases (AST and ALT) values ≤2.5 times ULN
• Adequate renal function defined by a creatinine clearance of ≥30 mL/min
• Adequate cardiac function defined by a left ventricular ejection fraction (LVEF) ≥40%, QTc <450 msec, and no evidence of clinically significant dysrhythmias on ECG
• Patient must have substantially recovered from clinically significant toxicities from prior therapies for multiple myeloma
• Fertile men and women must agree to use a medically effective contraception method throughout the treatment period. Premenopausal women of reproductive capacity and women less than 24 months post menopause must have a negative serum pregnancy test documented prior to study entry

Exclusion Criteria:

• Patients who never achieved at least minor response (MR) to at least one prior line of therapy
• Clinical spinal cord compression syndromes (unless patient has undergone treatment, for example, surgery or radiation therapy, and neurological findings are ≤ Grade 1 and patient is off corticosteroids for spinal cord edema or on a stable regimen of < 10 mg/day prednisone equivalent
• Clinical signs of brain involvement or leptomeningeal disease
• Plasma cell leukemia (plasma cells > 2000/cubic mm)
• Women who are pregnant or breast feeding
• Other serious illness or medical condition(s) (see protocol)
• Hypersensitivity to fluphenazine or other phenothiazines
• Currently being treated with hematopoietic growth factors other than erythropoietin (EPO). Treatment with hematopoietic growth factors may be started during the study with development, or worsening, of cytopenia
• Concurrent use of anticholinergics
• Concurrent use of phenothiazine and atypical antipsychotics
• Concurrent use of anti-seizure drugs, with the exception of gabapentin for treatment of neuropathy
• Grade 2 or higher persisting prior treatment-related neuropathy
• Concurrent use of systemic steroids with the exception of chronically administered steroids equivalent to ≤ 10 mg/day prednisone if patient has been on this therapy for ≥1month
• History of seizures or extrapyramidal symptoms
• History of other malignancies within the past 3 years, other than adequately treated non-melanoma skin cancer, or in situ carcinoma of the cervix, unless the other malignancy is quiescent and medical monitor approval is obtained