An Exploratory Clinical Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Autologous BCMA-targeted CAR-T Cell Injection in Participants With Relapsed/Refractory Light Chain Amyloidosis
Systemic light chain amyloidosis (AL amyloidosis) is the most common type of systemic amyloidosis, with diverse clinical manifestations and difficulties in diagnosis and treatment. AL amyloidosis may involve multiple organs; the kidney and heart are the most commonly involved organs. The treatment goal is to reduce monoclonal immunoglobulin light-chain levels, prevent further amyloid deposition in important organs, and alleviate or reverse organ dysfunction caused by amyloid deposition. The principal approach to achieve this goal is to eliminate the plasma-cell or B-cell clones producing abnormal light chains. For patients with relapsed/refractory AL amyloidosis, the protocol states that there is currently no suitable treatment method and that participation in clinical trials is recommended. This study evaluates targeted BCMA autologous CART cell injection in participants with relapsed/refractory light chain amyloidosis. The main purpose is to evaluate safety, preliminarily verify efficacy, and explore in vivo pharmacokinetics, pharmacodynamics, immunogenicity and related characteristics after infusion.
• 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%.