Autologous BCMA-targeted CAR-T Cell Injection for Relapsed/Refractory Light Chain Amyloidosis

Inclusion Criteria:

• The participant must personally sign an ethics-committee-approved informed consent form before study start.
• Age ≥18 years.
• Pathologically confirmed light chain amyloidosis.
• Relapsed/refractory light chain amyloidosis previously treated with 2 or more lines of therapy.
• dFLC >50 mg/L.
• Expected survival ≥12 weeks.
• ECOG score ≤2.
• Diagnosis of AL amyloidosis must meet the following conditions: (1) clinical manifestations, physical examination, laboratory or imaging examinations confirm tissue or organ involvement; (2) tissue biopsy pathology confirms amyloid deposition, and the precursor protein of amyloid protein is immunoglobulin light chain or heavy and light chain; and the participant is relapsed/refractory.
• Female participants of childbearing potential should agree to use effective contraception from the date of signing informed consent until 365 days after infusion. Effective contraception is defined as abstinence or contraception using methods specified in the protocol with an annual failure rate <1%.

• Adequate organ function before enrollment, meeting all of the following:

  • Absolute neutrophil count ≥1.0×10^9/L; granulocyte colony-stimulating factor (G-CSF) support is permitted.
  • Platelet count ≥50×10^9/L.
  • Hemoglobin ≥8 g/dL.
  • Bilirubin ≤1.5×upper limit of normal (ULN), except biliary obstruction caused by tumor compression.
  • ALT or AST ≤2.5×ULN; for participants with liver involvement, ≤5×ULN.
  • Mayo 2004 stage I-IIIa.
  • Stable coagulation function: INR ≤1.5 and APTT ≤1.2×ULN, except tumor-related anticoagulant therapy.
  • Baseline oxygen saturation on room air >92%.

Exclusion Criteria:

• Participants who have received the following prior treatments:

  • Prior gene therapy before enrollment.
  • Live vaccine injection within 4 weeks before enrollment.
  • Other interventional clinical study drug treatment within 12 weeks before leukapheresis.
• Central nervous system involvement or complete intestinal obstruction.
• Moderate or higher pleural effusion or ascites that is difficult to control with conventional treatment and requires continuous catheter drainage.
• Active malignancy within the past 5 years, unless it is a curable tumor and has been clearly cured.
• HBsAg positivity with abnormal peripheral blood HBV DNA testing; HCV antibody positivity with peripheral blood HCV RNA positivity; HIV antibody positivity; CMV DNA positivity; or positive syphilis RPR test.
• Uncontrolled active infection, except CTCAE grade <2 urogenital infection and upper respiratory tract infection.
• Severe heart disease, including but not limited to unstable angina, myocardial infarction within 6 months before screening, congestive heart failure (New York Heart Association [NYHA] class ≥III), positive six-minute walk test, interventricular septum and left ventricular posterior wall thickness >1.5 cm, or ventricular arrhythmia and atrioventricular block indicated by ambulatory electrocardiography.
• Hypertension that cannot be controlled by medication.
• Toxicity from prior treatment not recovered to baseline or ≤grade 1 according to NCI CTCAE v5.0, except alopecia and clinically insignificant laboratory abnormalities.
• Major surgery within 2 weeks before enrollment, or planned surgery during the waiting period before infusion or within 12 weeks after study treatment, except planned local anesthesia surgery.
• Solid organ transplantation.
• Pregnant or breastfeeding women.
• History of central nervous system disease, such as cerebral aneurysm, epilepsy, stroke, senile dementia or psychiatric disease, or disturbance of consciousness.
• Other systemic disease judged unstable by the investigator, including but not limited to severe hepatic, renal or metabolic disease requiring medication.
• Known life-threatening allergic reaction, hypersensitivity or intolerance to the CAR-T cell product or its components.
• Bleeding or severe thrombosis as judged by the investigator, hereditary/acquired bleeding or severe thrombosis, including hemophilia, coagulopathy, thrombocytopenia and hypersplenism, or current thrombolytic or anticoagulant therapy.
• Other conditions that the investigator considers unsuitable for enrollment.