aggressive relapsing remitting (RR) or secondary progressive (SP) multiple sclerosis
Conditions
Sponsors
Fondation Charcot Stichting
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. patients with aggressive RR or SP MS who failed to respond to approved immunomodulatory drugs (interferons beta, glatiramer acetate) and who cannot or do not wish to receive mitoxantrone or tysabri. 2. patients within =18 and = 55 years of age 3. patients with a disease duration of maximum 15 years 4. clinically definite RR or SP MS, according to Lublin and Reingold definition and the McDonald criteria 5. Expanded Disability Status Scale Score (EDSS) = 2.5 and = 5.5 6. patients in the RR phase with a poor prognosis because of frequent (= 2/year) and severe relapses (transient EDSS =3) likely leading to permanent disability or patients in the SP phase with clinical signs or symptoms of rapid progression over the last year equivalent to an increase in EDSS of >/ 1 point 7. = 1 gadolinium enhancing lesion(s) at screening 8. left ventricular ejection fraction = 50% 9. standard laboratory parameters within the normal range, including hematology (lymphocytes > 1000/mm³, ANC (absolute neutrophil count) =2000/ml, thrombocytes =100.000/ml) 10. male or female patients: NB: female patients of child-bearing potential should have a negative pregnancy test at the time of inclusion male and female patients within reproductive ages should agree to practice effective contraception during the trial and for 6 months following the last administration of PIX. 11. have given written informed consent prior to treatment, with the understanding that consent may be withdrawn at any time without prejudice Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. previous treatment with immunosuppressants (Mitoxantrone or other anthracyclines, Cyclophosphamide, Methotrexate, Azathioprine, rituximab, alemtuzumab …) in the past year 2. in case of a recent relapse, the time from start of recovery/end of relapse to study entry should be at least one month 3. any corticosteroids or ACTH in the month preceding study entry 4. patients with cardiac risk factors: prior history of congestive heart failure, myocardial infarction, uncontrolled ischemic heart disease, hypertension or malignant hemopathy 5. patients treated with potential cardiotoxic drugs 6. patients who are at medical risks because of systemic disease which might interfere with patient safety (e.g.: impairment of renal or hepatic function, severe infection, alcohol abuse or drug addiction) 7. patients with impaired intellectual functions or psychiatric disorders preventing normal cooperation during the trial 8. participation in any investigational study within 4 weeks prior to treatment start; patient must have recovered from all side effects of other investigational therapy 9. history of, or clinical signs or symptoms suggestive of HIV, HBV, HCV 10. any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To determine if four consecutive administrations of 120 mg/m² each of PIX (equivalent to 12 mg/m² mitoxantrone) will provide an effective immunosuppression as reflected by a lymphopenia = 1000/mm³ after completion of PIX administration. 2. To evaluate the effects of PIX on brain inflammatory lesions as demonstrated by MRI gadolinium enhancing and T2 lesions. ;Secondary Objective: 1. cardiac tolerance monitored by echocardiography and cardiotroponin T 2. immune changes as demonstrated by lymphocyte subset typing (CD3, CD4, CD8, B cells) and other immunological parameters 3. vital signs 4. side effects and adverse reactions 5. effects of treatment on relapse rate and disability progression (EDSS, 9HP test, 25 FWT). ;Primary end point(s): 1. Proportion of patients with a lymphopenia = 1000/mm³ at month 3. 2. Decrease in brain inflammatory lesions as demonstrated by MRI gadolinium enhancing lesions (Gd+ lesions) evolution: number of patients with new Gd+ lesions mean total number of Gd+ lesions mean total number of Gd+ lesions/scan mean number of new Gd+ lesions mean number of new Gd+ lesions/scan MRI scans will be performed within two weeks before the first study drug administration, and at months 6 and 12. | — |
Countries
France
Outcome results
None listed