Treatment of patients with autoantibody-positive autoimmune diseases and severe interstitial lung fibrosis with T lymphocytes transduced by RV-SFG.CD19.CD28.4-1BBzeta retroviral vector - a single center Phase I/II clinical trial (HD-CAR-ILD-1)

Prior treatment

• Immunosuppressive medication like a biological DMARD within 3 months, conventional synthetic DMARDs within 6 weeks or JAKi within 1 month be-fore leukapheresis with the exception of: - ≤ 30 mg prednisolone/d or equivalent at the time of leukapheresis and CAR T cell transfusion - Bridging/maintenance Mycophenolic acid/ Nintedanib. It must be stopped two weeks prior to leukapheresis, but can be continued be-tween leukapheresis and lymphodepletion, is stopped one week be-fore lymphodepletion and restarted at the earliest 4 weeks after CD19.CAR T cell therapy when suitable according to the treating phy-sician
• Severe concomitant disease (e.g. uncontrolled arterial hypertension, left heart failure NYHA III-IV, uncontrolled diabetes mellitus)
• Unstable angina and/or myocardial infarction within 3 months prior to screen-ing
• Any previous or concurrent malignancy with the exception of non-melanoma skin cancer, in situ carcinoma of the cervix or breast, prostate cancer up to Gleason score 6 treated curatively without evidence of recurrence ≥ 3 years prior to the study, or a primary malignancy which is in complete remission for ≥ 5 years

Other illness

• Antigen- or DNA/RNA positive hepatitis B or C
• HIV-positivity
• Uncontrolled acute life-threatening bacterial, viral or fungal infection at the time of inclusion into the study
• Patients with active CNS involvement of their autoimmune disease must not be included in the study

Lab values

• GFR < 30 mL/min/1.73 m2

Other

• Pregnant or nursing (lactating) women
• Intolerance to the excipients of the cell product
• Participation in another clinical trial at the time of screening
• Insufficient command of the German language

• Confirmed autoantibody-positive autoimmune-triggered lung fibrosis with im-paired pulmonary function of FVC < 70% (but >40%) and TLCO/VA <60% (but >25%) and/or TLCO SB <60% (but >25%), in the course of diseases like Rheumatoid Arthritis, Systemic Sclerosis, ANCA-associated vasculitis, anti-Synthetase Syndrome, Sjögren’s disease or other autoimmunopathies.
• Adequate organ function: - Renal function defined as: serum creatinine of ≤ 2 x ULN or eGFR ≥ 30 mL/min/1.73 m2 - Liver function defined as: • ALT ≤ 3 times the ULN for the respective age • Bilirubin ≤ 2.0 mg/dl with the exception of patients with hyper-bilirubinemia explained by Gilbert–Meulengracht Syndrome (may be included if total bilirubin is ≤ 3.0 x ULN and direct bili-rubin ≤ 1.5 x ULN) - minimum level of pulmonary reserve defined as ≤ grade 2 dyspnea and pulse oxygenation > 85% on room air and functional vital capacity FVC > 40% - Hemodynamic stability and LVEF ≥ 40% as confirmed by echocardi-ogram - In case of moderate or severe pulmoarterial hypertension: combina-tion therapy with at least 2 approved drugs (according to routine care) is mandatory
• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Absolute lymphocyte count (ALC) ≥ 400/mm3
• Age 18-70
• Women of child-bearing potential (defined as all women physiologically capa-ble of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for one year following CD19.CAR T cell therapy
• Ability to understand the nature of the trial and the trial related procedures
• Written informed consent must be obtained prior to any screening procedures