Phase I Clinical Trial of CD19-targeting Chimeric Antigen Receptor T Lymphocyte (MC-1-50) for the Treatment of Refractory Adult Systemic Lupus Erythematosus(SLE)
This is a single-arm, open, dose-increasing and dose-expanding phase I clinical trial to investigate the safety, tolerability and cytodynamic characteristics of MC-1-50 cell preparation, and to preliminatively observe the efficacy of MC-1-50 cell preparation in patients with refractory SLE, and to explore the applicable dose regimen for phase II clinical trials.
• The patient or their guardian agrees to participate in this clinical trial and sign the ICF, indicating their understanding of the purpose and procedures of this clinical trial and willingness to participate in the study;
• Age ≥ 18 years old , gender not limited;
• Patients diagnosed with SLE according to the 2019 EULAR/ACR classification criteria,And by hydroxychloroquine, sufficient glucocorticoid (≥1mg/kg/d prednisone or equivalent amount of other hormones), to less than 2Treatment with immunosuppressants (including cyclophosphamide, motecophanate, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide, etc.), and at least one approved biological agent (including titacept, Beliuzumab, etc.), with a total duration of treatment ≥3 months, still in a disease active state, or unable to tolerate conventional therapy;
• SLEDAI-2K score ≥7 points;
• Autoantibody test results are positive: ANA antibody positive and/or serum anti-DSDNA positive;
• Adequate renal, hepatic, pulmonary and cardiac function defined as:
‣ Cardiac function: Echocardiography indicates left ventricular ejection fraction ≥ 50%;
⁃ Renal function: serum creatinine ≤ 2.0 × ULN, or creatinine clearance rate ≥ 60ml/min (Cockcroft Gault formula);
⁃ Hepatic function: ALT and AST ≤ 3.0 × ULN (may be relaxed to ≤ 3.0 × ULN in cases of combined liver infiltration);
⁃ Total bilirubin ≤ 2.0 × ULN (Gilbert syndrome requires total bilirubin ≤ 3.0 × ULN);
⁃ Pulmonary function: Blood oxygen saturation is ≥ 92% in non oxygen state.
• No serious mental disorders;
• Meet standards for apheresis or venous blood collection, and no other cell collection contraindications;
• Women of childbearing age who have a negative blood pregnancy test and all subjects agree to use reliable and effective contraceptive methods (excluding safe period contraception) for contraception within one year after receiving MC-1-50 cell infusion from the time of signing the informed consent form. Including but not limited to: abstinence, implantable progestogen contraceptives that can inhibit ovulation; Intrauterine device (IUD); Intrauterine hormone release system; Spouse vasectomy; Compound hormone contraceptives that can inhibit ovulation (oral, vaginal, and transdermal); Progesterone contraceptives (oral or injectable) that can inhibit ovulation; When male subjects have sex with fertile women, they must agree to use barrier contraception (such as condom plus spermicidal foam/gel/film/emulsion/suppository). At the same time, participants should commit not to donate eggs (oocytes, oocytes) or sperm for assisted reproduction within one year after cell infusion.