PATIENTS AFFECTED BY MULTIPLE SCLEROSIS MedDRA version: 6.1 Level: HLT Classification code 10052785
Conditions
Interventions
Trade Name: THIOPLEX
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Thiotepa
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Trade
Sponsors
OSPEDALE S. RAFFAELE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: · multiple sclerosis defined by Mc Donald criteria; · age between 18 and 55; · EDSS score between 2 and 6.5; · RR or SP clinical course; · ability to give written informed consent; · treatment failure to second line therapy (i.d. Natalizumab, Mitoxantrone or Cyclophosfamide). Failure treatment is defined by the occurrence, after at least three-six months of therapy, of the following: a) at least one relapse or a documented rapid progression (progression is defined by an increase of at least 1 point at EDSS scale between 2.0 and 5.5 or 0,5 point between 5.5-6.5 over six months) b) an increase of at least two T2 lesions or the presence of at least one new enhancing lesion at MRI performed six months after the previous one. 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: · previous treatment with TBI or TLI; · treatment with interferons, Glatiramer acetate in 30 days before the ASCT; · treatments with steroids, Cyclophosphamide, Mitoxantrone, Azathioprine, plasma-exchange, immunoglobulins in 30 days before phase I; · impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit); · impaired renal function (Creatinine-clearance 1.5 x upper normal limit); · left ventricular ejection < 50%; · any other clinical, laboratory, instrumental abnormality that, on investigator?s opinion, could negatively affect the outcome of the treatment· recurrent or chronical infections; · pregnancy, breast feeding, patient?s non compliance to use valid birth control methods; · controindications for serial MRI (claustrophobia, metallic prothesis, cardiac pacemaker, tremor, spinal devices).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: · safety and feasibility of high-dose immunosuppression provided by the conditioning regimen with Thiotepa and Cyclophosphamide followed by Autologous Stem Cell Transplantation (CTCAE, TRM evaluations); · effect of treatment on inflammatory activity at MRI (reduction or absence of enhancing lesions); · effect of treatment on clinical course (progression evaluated with EDSS score evaluation and number of relapses).;Secondary Objective: · study of immunological recovery and regeneration of the immune repertoire after ASCT (regulatory T cell phenotype, effector T cell phenotype, cytochine, chemokine and growth factor release); · effect of treatment on MRI measures of neurodegeneration (brain atrophy, total lesion load, and non-conventional MRI metrics); · multiple sclerosis functional composite (MSFC) evaluation; · patient quality of life outcome evaluation (MSQoL); · fatigue (FSS) and depression (BDI) evaluation;Primary end point(s): · safety and feasibility of high-dose immunosuppression provided by the conditioning regimen with Thiotepa and Cyclophosphamide followed by Autologous Stem Cell Transplantation (CTCAE, TRM evaluations); · effect of treatment on inflammatory activity at MRI (reduction or absence of enhancing lesions); · effect of treatment on clinical course (progression evaluated with EDSS score evaluation and number of relapses). | — |
Countries
Italy
Outcome results
None listed