Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Fluphenazine in Treating Patients With Refractory Advanced Multiple Myeloma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed Over 18 Pharmaceutical / Industry IMMUNECON-FM-CL1 UPCC-IRB-5, UPCC-09405, UPCC-803972, NCT00335647

Objectives

1. Determine the safety of high-dose fluphenazine hydrochloride in patients with refractory advanced multiple myeloma.
2. Determine the pharmacological properties of this drug.
3. Determine the effectiveness of this drug in these patients.

Entry 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

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

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/mm³*
• Platelet count ≥ 50,000/mm³*
• 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]

Expected Enrollment

A total of 30 patients will be accrued for this study.

Outcomes

Safety
Efficacy

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.

Trial Contact Information

Trial Lead Organizations

Immune Control Incorporated

Contact Person		Ph: 610-941-2971 Email: plutes@immunecontrol.com

Registry Information
Official Title		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
Trial Start Date		2006-01-25
Trial Completion Date		2008-04-18
Registered in ClinicalTrials.gov		NCT00335647
Date Submitted to PDQ		2006-05-16
Information Last Verified		2008-04-20