Study of Eque-cel CAR-T Therapy in Newly Diagnosed Severe AL Amyloidosis

Prior treatment

• Subjects who have received any of the following treatments prior to enrollment:
  • Gene therapy before enrollment;
  • Live vaccine within 4 weeks before enrollment;
  • Other interventional clinical trial drugs within 12 weeks before leukapheresis.
• Use of therapeutic doses of corticosteroids (defined as prednisone or equivalent \>20 mg/day) within 7 days before screening, though physiological replacement, topical, and inhaled steroids are permitted.
• Presence of uncontrolled active infection within 7 days before peripheral blood mononuclear cell (PBMC) collection (excluding genitourinary system infections and upper respiratory tract infections \<CTCAE Grade 2).
• Receipt of any systemic therapy for AL amyloidosis within 14 days before PBMC collection.
• Undergoing major surgery within 14 days before PBMC collection, or planning surgery within 2 weeks after study treatment (subjects planning local anesthesia surgery are eligible to participate).
• Unresolved non-hematologic toxicity from prior therapy to baseline or ≤Grade 1 (per NCI-CTCAE v5.0, excluding alopecia and Grade 2 peripheral neuropathy).
• Subjects with bleeding or severe thrombosis symptoms as judged by the investigator, or with genetic/acquired bleeding and severe thrombosis conditions (including hemophilia, coagulopathy, thrombocytopenia, splenomegaly), or currently receiving thrombolytic or anticoagulant therapy.
• Subjects who have received solid organ transplantation.
• Participation in another interventional clinical trial within 1 month before signing the ICF.

Other illness

• Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA in peripheral blood; positive for hepatitis C virus (HCV) antibody with detectable HCV RNA in peripheral blood; positive for human immunodeficiency virus (HIV) antibody; positive for cytomegalovirus (CMV) DNA; positive for syphilis testing.
• Known life-threatening allergic reaction, hypersensitivity, or intolerance to cellular products or their components.
• Severe active cardiovascular disease with significant clinical symptoms despite treatment, including but not limited to unstable angina, myocardial infarction, and severe arrhythmia (excluding those with implanted implantable cardioverter-defibrillator \[ICD\] or pacemaker).
• Subjects with hypertension that cannot be controlled by medication.
• Subjects with a history of central nervous system disorders (e.g., cerebral aneurysm, epilepsy, stroke, dementia, psychosis) or consciousness impairment.
• Subjects with unstable systemic diseases as judged by the investigator, including but not limited to severe liver, kidney, or metabolic diseases requiring medical treatment.
• Diagnosis of malignancy other than multiple myeloma within 5 years before screening, excluding adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer post-radical surgery, or ductal carcinoma in situ of the breast post-radical surgery.
• Other conditions deemed unsuitable for enrollment by the investigator.

Other

• Subjects with suspected or confirmed symptoms of central nervous system (CNS) involvement by plasma cell tumors.
• Bone marrow plasma cells \>30% with clinical symptoms of multiple myeloma accompanied by osteolytic bone lesions.
• Women who are pregnant, breastfeeding, or planning to become pregnant.
• Subjects who do not agree to or have not completed the signing of the ICF.

• Subjects aged ≥18 years, regardless of gender.
• Performance status: Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
• Clinically diagnosed with newly diagnosed AL (light chain) amyloidosis, classified as Mayo Stage IIIb per the revised 2004 Mayo Clinic staging system at screening, with serum N-terminal pro-brain natriuretic peptide (NT-proBNP) \>8500 ng/L and serum cardiac troponin T (cTnT) \>0.035 μg/L or cardiac troponin I (cTnI) \>0.01 g/L.
• Presence of measurable hematologic disease at screening, defined as at least one of the following:
  • Difference in free light chains (dFLC) \>4 mg/dL, or
  • Involved free light chain (iFLC) \>4 mg/dL with abnormal kappa/lambda (κ/λ) ratio, or
  • Serum protein electrophoresis (SPEP) M protein \>0.5 g/dL.
• Histopathological diagnosis of amyloidosis based on polarized light microscopy of Congo red-stained tissue specimens showing green birefringence, with confirmation of AL-derived amyloid deposits by at least one of the following methods:
  • Immunohistochemistry/immunofluorescence,
  • Mass spectrometry,
  • Electron microscopy for characteristic appearance/immunoelectron microscopy.
• Presence of clonal plasma cells in bone marrow, detectable by light microscopy or flow cytometry.
• Presence of M protein in blood or urine, with exclusion of multiple myeloma, Waldenström macroglobulinemia, or other lymphoplasmacytic proliferative disorders.
• Organ involvement: At least one organ affected (kidney, heart, liver, nervous system, gastrointestinal tract, lung, soft tissue) as per consensus guidelines.
• Expected survival time ≥12 weeks.
• Subjects must have adequate organ function, meeting all of the following laboratory criteria prior to enrollment:
  • Complete blood count: Absolute neutrophil count (ANC) ≥1×10⁹/L; absolute lymphocyte count (ALC) ≥0.3×10⁹/L.
  • Hemoglobin \>60 g/L (no red blood cell \[RBC\] transfusion within 7 days prior to testing; use of recombinant human erythropoietin allowed).
  • Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× upper limit of normal (ULN); total serum bilirubin ≤1.5× ULN.
  • Renal function: Creatinine clearance (CrCl) ≥30 mL/min as calculated by the Cockcroft-Gault formula.
  • Coagulation function: Fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5× ULN; prothrombin time (PT) ≤1.5× ULN.
  • Blood oxygen saturation \>91%.
  • Echocardiogram showing left ventricular ejection fraction (LVEF) ≥40%.
  • Systolic blood pressure (SBP) ≥90 mmHg (oral vasopressor support allowed).
• Subjects and their spouses agree to use effective contraceptive methods (tools or medications) from the time of signing the informed consent form until one year after CAR-T cell infusion.
• Subjects voluntarily sign the informed consent form (ICF).