Adaptive Dual-Target CAR-T Cells for Relapsed or Refractory Hematologic Malignancies

Korábbi kezelés

• Active symptomatic CNS involvement requiring escalating therapy; previously treated/stable CNS disease may be allowed if defined prospectively in the final protocol.
• Prior gene-modified cellular therapy within 12 weeks before leukapheresis, or unresolved >= Grade 3 toxicity from prior anticancer therapy
• Prior solid organ transplant.

Más betegség

• - Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection, or clinical sepsis.
• Active autoimmune disease requiring systemic immunosuppression, except limited replacement-dose steroids or protocol-permitted topical/inhaled therapy.
• Clinically significant cardiovascular disease, uncontrolled arrhythmia, decompensated heart failure, myocardial infarction within 6 months, or recent stroke within 6 months.
• Uncontrolled HIV, HBV, or HCV viremia.
• Another active malignancy requiring systemic therapy, unless low-risk and definitively treated per protocol-defined exceptions.
• Known hypersensitivity to fludarabine, cyclophosphamide, or critical product excipients.
• Inability to manufacture a releaseable CAR-T product or failure to meet module-specific product-release criteria.
• Any medical, psychiatric, or social condition that, in the investigator's judgment, would increase risk, impair compliance, or confound interpretation of study results.

Egyéb

• Need for urgent cytoreduction such that manufacturing delay would create unacceptable clinical risk.
• Pregnancy or breastfeeding.

• Age 18 to 75 years at the time of consent.
• Pathologically or cytologically confirmed eligible disease: B-ALL; B-cell NHL/CLL/SLL; multiple myeloma/plasma cell leukemia; AML/high-risk MDS/BPDCN; or T-ALL/T-LBL/peripheral T-cell lymphoma.
• Relapsed or refractory disease after at least 2 prior lines of therapy, or no curative/approved standard option judged appropriate by the investigator.
• Central laboratory confirmation that at least one active dual-target module is suitable based on malignant-cell antigen co-expression and safety review.
• Measurable or otherwise evaluable disease by disease-specific response criteria.
• ECOG performance status 0 to 2.
• Adequate organ function: LVEF >= 45%; creatinine clearance >= 40 mL/min; AST/ALT <= 3 x ULN; total bilirubin <= 1.5 x ULN unless due to Gilbert syndrome; oxygen saturation >= 92% on room air.
• Adequate hematologic reserve unless cytopenia is clearly disease-related.
• Ability to undergo leukapheresis and willingness to comply with study procedures and follow-up.
• If prior allogeneic HSCT: at least 100 days from transplant, no uncontrolled GVHD, and no systemic immunosuppression above physiologic steroid replacement.
• Negative pregnancy test for participants of childbearing potential and agreement to use effective contraception during protocol-defined risk periods.
• Written informed consent obtained before any study-specific procedure.