Study of Fluphenazine in Relapsed or Relapsed-and-Refractory Multiple Myeloma

Immune Control

Status and phase

Unknown

Phase 1

Conditions

Multiple Myeloma

Treatments

Drug: Fluphenazine HCl

Study type

Interventional

Funder types

Industry

Identifiers

NCT00821301

FM-CL2

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of fluphenazine in patients with advanced multiple myeloma. The study will also describe the efficacy of this drug.

Full description

This is a multicenter, dose-escalating, Phase 1b trial in patients with relapsed or relapsed-and-refractory multiple myeloma. Patients will be dosed on Days 1 and 8 of each 21 day cycle.

This study will be conducted in two parts. In Part 1, the MTD determining portion of the study, patients will be enrolled in cohorts of 3 patients at each dose level. At least 3 patients will complete 21 days at each dose level and will be evaluated for safety and tolerability before additional patients are treated at higher doses. Doses will be increased following a modified Fibonacci scheme.

In Part 2, twelve additional patients will be enrolled at the MTD determined in Part 1 (or the dose for the highest dose cohort completed if the MTD has not been reached) to further evaluate the safety, tolerability, and preliminary efficacy of this dose regimen.

Serum fluphenazine pharmacokinetic studies will be performed during the first cycle of the therapy in all Part 1 and Part 2 consenting patients.

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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