MB-CART2019.1 in Refractory Multiple Sclerosis

Exclusion Criteria

• •Patients will be entered into this trial only if they meet none of the following criteria:
• •1. For relapsing and progressive MS forms: the disability status according to the EDSS scale is larger than 7.0 or the age is larger than 55 years.
• •Only applicable for progressive MS (PPMS/SPMS), where the disease duration is longer than 15 years.
• •2. History of a malignancy unless disease free for ≥5 years with the exception of basal or squamous cell skin cancer
• •3. Known history of and/or active infection with hepatitis B (hepatitis B surface antigen positive)
• •4. Known history of infection with hepatitis C virus unless treated and confirmed to be polymerase chain reaction (PCR) negative
• •5. Any active uncontrolled bacterial, viral or fungal infection
• •6. A history of and/or active infection with human immunodeficiency virus (HIV)
• •7. A history of active or latent tuberculosis (TB); TB testing should be performed at screening (Quantiferon test). Confirmed active or latent TB the patient can be re-screened after full completion of anti-tuberculosis treatment (9 months of Isoniazide therapy)
• •8. History of neuromyelitis optica spectrum disorder (NMOSD) or MOG antibody associated disease.
• •9. History of CNS or spinal cord tumor, metabolic or infectious causes of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis or non MS-progressive neurological condition affecting the ability to perform the study assessments
• •10. History of cytopenia consistent with MDS diagnosis
• •11. History of sickle cell anemia or other hemoglinopathies
• •12. Primary immune deficiency disease
• •13. Patients with positive antiphospholipid antibodies, anti-cardiolipin or lupus anticoagulant.
• •14. History of moderate or worse renal impairment (eGFR \< 30 ml/min/1.73 m2)
• •15. Prevalent inflammatory diseases of the GI tract (e.g. Inflammatory bowel disease, Peptic ulcer) which could result in a higher risk for gastrointestinal perforation.
• •16. The following cardiac conditions:
• •New York Heart Association Stage III or IV congestive heart failure Myocardial infarction or coronary artery bypass graft ≤ 6 months prior to enrollment History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
• •17. History of severe non-ischemic cardiomyopathy Medications:
• •Systemic corticosteroids \>10 mg within 7 days prior to leukapheresis; T cell targeting drugs (e.g. mycophenolate mofetil, calcineurin inhibitors) within 21 days prior to leukapheresis, Previous CAR T cell therapy, Live vaccines within 30 days prior to leukapheresis, Current Cytotoxic drugs Other MS disease modifying drugs (as stated in 5.8.1.)
• •18. Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory preparative lymphodepletion or rescue medication/salvage therapies for treatment related toxicities;
• •19. Contraindication of trial related procedures as judged by the investigator
• •20. Pregnant of breast-feeding females; female patients of child-bearing potential not willing to practice a highly effective form of birth control from leukapheresis and for 12 months after dosing the IMP
• •21. Concurrent participation in another interventional trial
• •22. Inability to understand the procedures and risks associated with the Trial.
• •23. Any additional contraindication of trial related procedures as judged by the investigator