Comparison of B-cell Depletion by Rituximab and Anti-CD 19 CAR-T Therapy in Patients With Rheumatoid Arthritis

Exclusion Criteria

• •ANC \< 1.000/mm3, ALC \< 500/mm3 or hemoglobin \< 8g/dl, absolute CD3+T cell count \< 100/µl
• •Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh B or C), or heart andor pulmonary (NYHA III or IV, blood oxygenation \<92%) function
• •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to partici-pate in the study or confounds the ability to interpret data from the study
• •Prior treatment with anti-CD19 antibody therapy, adoptive T cell thera-py or any prior gene therapy product (e.g. CAR T cell therapy)
• •Only in phase II: Prior treatment of rituximab \< 7 months before base-line OR ≥ 7 months before baseline and B cell level \< 0.1/nl
• •History of bone marrow/ hematopoietic stem cell or solid organ trans-plantation
• •csDMARD other than MTX at baseline
• •Any concomitant severe active infection, e.g. HIV, hepatitis B or C, SARS-CoV-2 (COVID-19), or active tuberculosis as defined by a posi-tive Quantiferon TB-test. If presence of latent tuberculosis is estab-lished then treatment according to local guidelines must have been ini-tiated prior to enrollment
• •Pregnant or lactating females
• •Females who are intending to conceive during the study
• •Known hypersensitivity to any drug components
• •Malignancy in the last 5 years before screening (except basal or squamous cell skin cancer)
• •Requirement for immunization with live vaccine during the study peri-od or within 14 days preceding leukapheresis,
• •Subjects who are younger than 18 years or are incapable to under-stand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG),
• •Subject who Hhave a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the Investigator, may in-crease the risks associated with study participation or study agent ad-ministration, or may interfere with interpretation of results,
• •Subjects who possibly are dependent on the Sponsor, the Principal In-vestigator or Investigator (e.g. family members).
• •Subjects who are institutionalized by order of court or public authority
• •Subjects participating in another clinical trial with an investigational medicinal product or medical device (3 months before this trial)