Inaticabtagene Autoleucel Injection in the Treatment of Refractory Systemic Lupus Erythematosus-related Immune Thrombocytopenia

Prior treatment

• Major surgery that was assessed as unsuitable by the investigators within 4 weeks before screening.
• Patients vaccinated with a live vaccine within 6 weeks prior to screening.
• Patients with deep vein thrombosis within 6 months prior to screening, or a history of pulmonary embolism.
• Patients participating in any other interventional clinical study or receiving treatment of an active investigational drug within 3 months or 5 half-lives for launched drugs prior to Inaticabtagene Autoleucel Injection infusion.
• Patients previously received CAR-T cell therapy.

Other illness

• Severe active central nervous system (CNS) lupus, including seizures, psychosis, cerebrovascular accidents, or CNS vasculitis requiring therapeutic intervention within 60 days after baseline.
• Merge active infections (such as sepsis, bacteremia, mycosis, uncontrolled lung infections, and active tuberculosis).
• Hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) are positive; Hepatitis B e antibody (HBe Ab) and/or hepatitis B core antibody (HBcAb) are positive, and the number of HBV-DNA copies is greater than the measurable lower limit; Hepatitis C (HCV) antibody positive; positive for human immunodeficiency virus (HIV) antibodies; positive for syphilis antibody (TP Ab);
• Patients with concurrent active malignancy within the past five years, those with a history of malignancy but cuired are eligible.
• Patients with a history of epilepsy, cerebral ischemia/hemorrhage, cerebellar diseases, or other active central nervous system disorders;
• Patients with hypersensitivity reactions to the components of Inaticabtagene Autoleucel Injection.

Lab values

• Dialysis patients or creatinine clearance rate less than 30mL/min.
• The patient's heart meets any of the following conditions:
  • Left ventricular ejection fraction (LVEF) ≤ 45%; New York Heart Association (NYHA) Grade III or IV congestive heart failure or active heart disease; Severe arrhythmias that require treatment (excluding atrial fibrillation and paroxysmal supraventricular tachycardia); QTcB interval ≥ 450ms for males and ≥ 470ms for females (QTcB=QT/RR1/2); Have had myocardial infarction, bypass or stent surgery within the 6 months prior to the study; Other heart diseases that have been determined by researchers to be unsuitable for inclusion;

Other

• Pregnancy or breastfeeding.
• Patients with clinically significant pleural effusion during screening.
• Patients with a life expectancy of less than 6 months.

• Age range: 18-70 years (including 18 and 70 years), regardless of gender.
• Clinically diagnosed with Refractory Systemic Lupus Erythematosus-related Immune Thrombocytopenia according to the revised criteria of ACR in 1997 or EULAR/ACR in 2019. At least two consecutive blood routine tests showing platelet counts \<50×10\^9/L; Peripheral blood smear microscopy showed no significant abnormalities in the morphology of blood cells; The morphological characteristics of bone marrow cells are consistent with immune thrombocytopenia. Treated at least 1 course of MP shock therapy or high-dose steroids, combined with one or more immunosuppressive agents (including biologics) for at least 3 months but not achieving partial remission, or the efficacy cannot be maintained during the steroid reduction process.
• During the study period, the use of corticosteroids at a dose not exceeding 10mg prednisone or its equivalent, all immunosuppressants (excluding hydroxychloroquine) should be discontinued.
• Women of childbearing potential must have a negative blood pregnancy test 7 days prior to trial conditioning therapy; any male and female patients of childbearing potential must agree to use an effective method of contraception throughout the study and for at least 2 year following infusion of CAR-T cells. Childbearing potential is biologically capable of bearing a living baby and sexually active. Female patients who were not of childbearing potential (ie, met at least 1 of the following criteria):
  • Hysterectomy or oophorectomy, or
  • Medically confirmed ovarian failure, or medically confirmed postmenopausal (cessation of menses for at least 12 consecutive months in the absence of pathological or physiological causes).
• Adequate organ function according to the following criteria:
  • Aspartate aminotransferase (AST) ≤ 3 times of upper limit of normal (ULN);
  • Alanine aminotransferase (ALT) ≤ 3 times ULN;
  • Total serum bilirubin ≤ 2 times ULN unless the patient has documented Gilbert's syndrome; patients with Gilbert's syndrome who have bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN may be included;
  • Serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 60 mL/min (Cockcroft and Gault formula), Patients with lupus nephritis may relax the conditions appropriately according to the judgment of the investigator;
  • Must have minimal pulmonary reserve and oxygen saturation \> 91% in a nonoxygenated state;
  • Lymphocyte count \> 0.4 × 109/L.