relapsing-remitting multiple sclerosis MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Lemtrada
Product Name: alemtuzumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: alemtuzumab
CAS Number: 216503-57-0
Other descriptive name: ALEMTUZUMAB
Concentration uni
Sponsors
University Medical Centre Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent and agreement to comply to study protocol 2. Age: 18-55 years 3. EDSS: 0.0 – 6.0 4. RRMS according to McDonald 20108 5. 3 mm > 3 months before or after relapse onset or 2 new T2-lesions or - On-going signs of MRI activity in the last 6 months (either Gd-enhancing of = 3 mm lesion at any exam in the last year; or more than 5 new T2 lesions (= 3 mm)) or - Patients stable under natalizumab but who have to stop treatment due to an increasing PML risk are defined as active, if a MRI within 6 months after termination of natalizumab shows new T2 or Gd-enhancing lesions and at least one other treatment failure prior to natalizumab is documented 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 50 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Secondary or primary progressive MS 2. Pregnancy, or other medical condition incompatible with aHSCT 3. Any treatment or medical condition that, according to the haematologist / transplant specialist precludes the use of aHSCT 4. John Cunningham virus (JCV) antibody index of > 1.5 in previously natalizumab-treated patients, if a negative CSF JCV-PCR prior to screening is not available 5. Relapse during 30 days before initiation of treatment. If a relapse occurs during this period and eligibility criteria are otherwise fulfilled, start of treatment will be delayed until at least 30 days after receiving steroids. 6. Concurrent clinically significant (as determined by the investigators and haematologist / transplant specialist) cardiac, immunological, pulmonary, neurological, renal or other major disease such as: - Prominent cardial disease (Left ventricular ejection fraction (LVEF) 1 cm) - Cerebrovascular disease - Renal disease (creatinine clearance < 30 ml/min/m2) - Respiratory disease (DLCO < 40% predicted) - Active bleeding or clotting disease - History of human immunodeficiency virus (HIV) or positive HIV antibody testing - Any uncontrolled acute or chronic infection, including HIV, hepatitis B surface antigen positivity and hepatitis C PCR positivity - Cancer except in situ cervix or cutaneous 7. Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the patient returning for follow-up visits on schedule. Unwillingness to use contraception. 8. Previous participation in this study, previous treatment with aHSCT or already both comparators 9. Ongoing immunotherapy. Treatment with interferon or glatirameracetate will need no wash-out. Treatment pause before ocrelizumab/alemtuzumab or aHSCT will be: - for dimethylfumarate and fingolimod: 8 weeks - for natalizumab: 8 weeks - for ocrelizumab: 12 weeks - for alemtuzumab: 12 months - for teriflunomide: 4 weeks after elimination with cholestyramine - for cladribine: 24 weeks 10. Patients with cognitive impairments who are unable to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To gain further evidence for clinical efficacy of aHSCT in active RRMS compared to ocrelizumab or alemtuzumab 2. To gain further knowledge on safety, tolerability and toxicity of aHSCT in MS ;Secondary Objective: 1. To gain further knowledge on the quality of life, daily functioning and long-term disability of patients treated with aHSCT with a special focus on neurocognitive functioning and on MRI measurements of neurodegeneration 2. To gain further knowledge on negative and positive predictors for aHSCT response in MS ;Primary end point(s): Time to treatment failure as assessed by failure of NEDA (no evidence of disease) activity during follow-up as defined by: a. 3 months confirmed EDSS progression b. confirmed relapse c. new/enlarging T2-hyperintense lesion on MRI d. any Gd-enhancing lesion on MRI;Timepoint(s) of evaluation of this end point: a. after 3 months b., c., d. after 6, 12, 18 and 24 months; after that every 6 months until last patient has 24 months of follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: a. EDSS change and EDSS improvement b. Annualized relapse rate c. Number of new T2 lesions d. Number of Gd-enhancing lesions e. Multiple sclerosis functional composite (MSFC) change f. Hamburg quality of life scale in MS (HAQUAMS) g. Percentage Brain Volume Change (PBVC) h. Grey and white matter atrophy Safety: a. Rate of AE / SAE including NCI grade 3 and 4 non-haematological toxicities;Timepoint(s) of evaluation of this end point: after 6, 12, 18 and 24 months; after that every 6 months until last patient has 24 months of follow-up | — |
Countries
Germany
Contacts
Public ContactNicolaus Kroeger
University Medical Centre Hamburg-Eppendorf
Outcome results
None listed