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Phase 1b Single Arm, Open Label, Multi-Center Study of Fluphenazine HCl Monotherapy in Relapsed or Relapsed-and-Refractory Multiple Myeloma

Phase 1
18 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

Phase 1b Single Arm, Open Label, Multi-Center Study of Fluphenazine HCl Monotherapy in Relapsed or Relapsed-and-Refractory Multiple Myeloma

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.

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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tolerability of fluphenazine.

Outcome Time Frame:

21 day treatment cycle(s)

Safety Issue:


Principal Investigator

Bruce A Silver, M.D., FACP

Investigator Role:

Study Director


United States: Food and Drug Administration

Study ID:




Start Date:

December 2008

Completion Date:

October 2010

Related Keywords:

  • Multiple Myeloma
  • Multiple myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Hospital of the University of Pennsylvania Philadelphia, Pennsylvania  19104
University of Pittsburgh Cancer Institute Hillman Cancer Center Pittsburgh, Pennsylvania  15232
Cancer Therapy and Research Center at the UT Health Sciences Center at San Antonio San Antonio, Texas  78229