Multiple Sclerosis
Conditions
Brief summary
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
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.
Interventions
None listed
Sponsors
EMD Serono
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Congestive Heart Failure (Treatment Phase) | up to 36 months | Number of patients experiencing congestive heart failure during the treatment phase of the trial |
| Congestive Heart Failure (Annual Follow-Up Phase) | up to 5 years | Number of patients experiencing congestive heart failure during the annual follow-up phase of the trial |
| Left Ventricular Ejection Fraction (Treatment Phase) | up to 36 months | Number of patients with left ventricular ejection fraction test results that decreased below 50% during the treatment phase of the trial |
| Left Ventricular Ejection Fraction (Annual Follow-Up Phase) | up to 5 years | Number of patients with left ventricular ejection fraction test results that decreased below 50% during the annual follow-up phase of the trial |
| Serious Infections (Treatment Phase) | up to 36 months | Number of serious infections during the treatment phase of the trial |
| Serious Infections (Annual Follow-Up Phase) | up to 5 years | Number of serious infections during the annual follow-up phase of the trial |
| IV Antibiotics (Individual Drugs Unspecified) Utilized Due to Serious Infection (Treatment Phase) | up to 36 months | Number of subjects in whom IV antibiotics were utilized due to serious infection during the treatment phase |
| IV Antibiotics (Individual Drugs Unspecified) Utilized Due To Serious Infection (Annual Follow-Up Phase) | up to 5 years | Number of subjects in whom IV antibiotics were utilized due to serious infection during the annual follow-up phase |
| Severe Neutropenia (Treatment Phase) | up to 36 months | Number of infections associated with severe neutropenia at onset during the treatment phase |
| Severe Neutropenia (Annual Follow-Up Phase) | up to 5 years | Number of infections associated with severe neutropenia at onset during the annual follow-up phase |
| Clinical Relapses (Treatment Phase) | up to 36 months | Number of clinical relapses reported during the treatment phase of the trial |
| Clinical Relapses (Annual Follow-Up Phase) | up to 5 years | Number of clinical relapses reported during the annual follow-up phase of the trial |
| 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 | up to 5 years | Outcomes are presented separately above apart from adverse events which are presented in the adverse event section |
Countries
United States
Participant flow
Recruitment details
Trial Initiation Date: 17 October 2000 (date of first subject first visit). Trial Completion Date 15 July 2008 (date of last subject last visit). 46 centers enrolled at least one subject.
Participants by arm
| Arm | Count |
|---|---|
| Novantrone Therapy Novantrone, 12 mg/m2 intravenously once every 3 months, until a 140 mg/m2 cumulative dose was reached | 509 |
| Total | 509 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative withdrawal | 30 |
| Overall Study | Changing physicians | 38 |
| Overall Study | Death | 12 |
| Overall Study | Lost to Follow-up | 70 |
| Overall Study | Other | 95 |
| Overall Study | Patient's decision | 92 |
Baseline characteristics
| Characteristic | Novantrone Therapy |
|---|---|
| Age Continuous | 46 years |
| Age, Customized 18 - 70 years | 509 participants |
| Age, Customized <=18 years | 0 participants |
| Region of Enrollment United States | 509 participants |
| Sex: Female, Male Female | 344 Participants |
| Sex: Female, Male Male | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 509 |
| serious Total, serious adverse events | 102 / 509 |
Outcome results
Primary
Clinical Relapses (Annual Follow-Up Phase)
Number of clinical relapses reported during the annual follow-up phase of the trial
Time frame: up to 5 years
Population: participants with annual follow up data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Clinical Relapses (Annual Follow-Up Phase) | 60 number of relapses |
Primary
Clinical Relapses (Treatment Phase)
Number of clinical relapses reported during the treatment phase of the trial
Time frame: up to 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Clinical Relapses (Treatment Phase) | 185 number of relapses |
Primary
Congestive Heart Failure (Annual Follow-Up Phase)
Number of patients experiencing congestive heart failure during the annual follow-up phase of the trial
Time frame: up to 5 years
Population: participants with annual follow up data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Congestive Heart Failure (Annual Follow-Up Phase) | 4 participants |
Primary
Congestive Heart Failure (Treatment Phase)
Number of patients experiencing congestive heart failure during the treatment phase of the trial
Time frame: up to 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Congestive Heart Failure (Treatment Phase) | 6 participants |
Primary
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
Time frame: up to 5 years
Population: participants with annual follow up data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | IV Antibiotics (Individual Drugs Unspecified) Utilized Due To Serious Infection (Annual Follow-Up Phase) | 0 participants |
Primary
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
Time frame: up to 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | IV Antibiotics (Individual Drugs Unspecified) Utilized Due to Serious Infection (Treatment Phase) | 40 participants |
Primary
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
Time frame: up to 5 years
Population: participants with annual follow up data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Left Ventricular Ejection Fraction (Annual Follow-Up Phase) | 14 participants |
Primary
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
Time frame: up to 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Left Ventricular Ejection Fraction (Treatment Phase) | 27 participants |
Primary
Serious Infections (Annual Follow-Up Phase)
Number of serious infections during the annual follow-up phase of the trial
Time frame: up to 5 years
Population: participants with annual follow up data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Serious Infections (Annual Follow-Up Phase) | 0 number of infections |
Primary
Serious Infections (Treatment Phase)
Number of serious infections during the treatment phase of the trial
Time frame: up to 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Serious Infections (Treatment Phase) | 50 number of infections |
Primary
Severe Neutropenia (Annual Follow-Up Phase)
Number of infections associated with severe neutropenia at onset during the annual follow-up phase
Time frame: up to 5 years
Population: participants with annual follow up data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Severe Neutropenia (Annual Follow-Up Phase) | 0 number of infections |
Primary
Severe Neutropenia (Treatment Phase)
Number of infections associated with severe neutropenia at onset during the treatment phase
Time frame: up to 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novantrone Therapy | Severe Neutropenia (Treatment Phase) | 9 number of infections |
Primary
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
Time frame: up to 5 years