Prospective, Open-label Tolerability and Safety Monitoring Study of Novantrone in a Selected Cohort of Multiple Sclerosis Patients

Study Overview
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Brief Summary
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The overall objective of this study is to collect data relevant to the tolerability of Novantrone® therapy in patients with multiple sclerosis (MS) using dosing and monitoring recommendations specified in the package insert.

Detailed Description
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This phase IV, multicenter, prospective, open-label tolerability and safety monitoring study will enroll a select cohort of 500 multiple sclerosis patients receiving commercially available Novantrone®. The patients will be assessed every 3 months during treatment followed by annual assessment for a total of five (5) years. The select cohort of MS patients enrolled will have secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting disease (i.e., patients whose neurological status is significantly abnormal between relapses). The overall objective of this study is to collect data relevant to the tolerability of Novantrone® therapy in patients with multiple sclerosis (MS) using dosing and monitoring recommendations specified in the package insert.

Official Title
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Prospective, Open-label Tolerability and Safety Monitoring Study of Novantrone in a Selected Cohort of Multiple Sclerosis Patients

Conditions
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Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible for inclusion into this study, the subjects must fulfill all of the following criteria: Platelet count >100,000 cells/µL Granulocyte count > 2000 cells/µL Age 18-65 years Negative pregnancy test for female patients who are biologically capable of becoming pregnant, even if they are taking birth control For patients of reproductive age, agreement to practice effective contraception throughout the study and for 6 months following the last administration of Novantrone® Signed Inform Consent. Exclusion Criteria: To be eligible for inclusion in this study the subjects must not meet any of the following criteria: Presence of cardiac risk factors: History of congestive heart failure LVEF < 50% determined by echocardiography or MUGA Previous treatment with Novantrone®, other anthracenediones, or anthracyclines Prior mediastinal radiotherapy or total lymphoidal irradiation AST, ALT, bilirubin > 2x upper limits of normal Severe untreated infection (including current urinary tract infection) Nursing or pregnant women)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Congestive Heart Failure (Treatment Phase) | Number of patients experiencing congestive heart failure during the treatment phase of the trial | up to 36 months | 
| Congestive Heart Failure (Annual Follow-Up Phase) | Number of patients experiencing congestive heart failure during the annual follow-up phase of the trial | up to 5 years | 
| Left Ventricular Ejection Fraction (Treatment Phase) | Number of patients with left ventricular ejection fraction test results that decreased below 50% during the treatment phase of the trial | up to 36 months | 
| Left Ventricular Ejection Fraction (Annual Follow-Up Phase) | Number of patients with left ventricular ejection fraction test results that decreased below 50% during the annual follow-up phase of the trial | up to 5 years | 
| Serious Infections (Treatment Phase) | Number of serious infections during the treatment phase of the trial | up to 36 months | 
| Serious Infections (Annual Follow-Up Phase) | Number of serious infections during the annual follow-up phase of the trial | up to 5 years | 
| IV Antibiotics (Individual Drugs Unspecified) Utilized Due to Serious Infection (Treatment Phase) | Number of subjects in whom IV antibiotics were utilized due to serious infection during the treatment phase | up to 36 months | 
| IV Antibiotics (Individual Drugs Unspecified) Utilized Due To Serious Infection (Annual Follow-Up Phase) | Number of subjects in whom IV antibiotics were utilized due to serious infection during the annual follow-up phase | up to 5 years | 
| Severe Neutropenia (Treatment Phase) | Number of infections associated with severe neutropenia at onset during the treatment phase | up to 36 months | 
| Severe Neutropenia (Annual Follow-Up Phase) | Number of infections associated with severe neutropenia at onset during the annual follow-up phase | up to 5 years | 
| Clinical Relapses (Treatment Phase) | Number of clinical relapses reported during the treatment phase of the trial | up to 36 months | 
| Clinical Relapses (Annual Follow-Up Phase) | Number of clinical relapses reported during the annual follow-up phase of the trial | up to 5 years | 
| Symptomatic CHF, Left Ventricular Ejection Fraction - Prior to Each Dose • Serious Infections, IV Antibiotics, or Assoc w/ Severe Neutropenia-evaluated. Novantrone Admin - Per PI • SAE, Clinical Relapses | Outcomes are presented separately above apart from adverse events which are presented in the adverse event section | up to 5 years |