Dual-Target GD2/B7-H3 CAR-NK Cells for Pediatric Relapsed or Refractory Neuroblastoma

Korábbi kezelés

• Active grade >= 2 graft-versus-host disease, or systemic immunosuppression for treatment/prevention of graft-versushost disease within the protocol-defined washout period after prior allogeneic transplant.
• Prior genetically modified cellular therapy within the protocol-defined washout window, or unresolved clinically significant toxicity from prior cell therapy.

Más betegség

• Active uncontrolled infection, including bacteremia, uncontrolled viral infection, or invasive fungal disease.
• Symptomatic or unstable central nervous system disease requiring urgent medical intervention.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Clinically significant uncontrolled cardiovascular, pulmonary, hepatic, renal, or neurologic disorder that would increase study risk.
• Known hypersensitivity to fludarabine, cyclophosphamide, study-product components, or supportive-care medications required by the protocol.
• Known uncontrolled HIV infection or uncontrolled hepatitis B or C.
• Any medical, psychosocial, or logistical condition that, in the investigator's judgment, would make study participation unsafe or would impair protocol adherence.

Egyéb

• Pregnancy or breastfeeding.

• Age 12 months to 21 years at consent/assent.
• Histologically confirmed neuroblastoma or ganglioneuroblastoma with relapsed, refractory, progressive, or persistent high-risk disease for which no curative standard option is available.
• Measurable or evaluable disease according to revised International Neuroblastoma Response Criteria (rINRC), including MIBG-avid disease, CT/MRI-evaluable soft-tissue disease, and/or bone marrow disease.
• Tumor material available for central assessment of GD2 and B7-H3 expression; at least one target must be positive.
  • GD2 is treated as the core target and B7-H3 as the complementary target for correlative target-prioritization analyses.
• Prior exposure to standard neuroblastoma therapy, including anti-GD2-based therapy, unless contraindicated, unavailable, or declined for a documented medical reason.
• Lansky or Karnofsky performance score >= 50.
• Life expectancy >= 8 weeks.
• Recovery from clinically significant acute toxicities of prior therapy and protocol-defined washout from chemotherapy, biologics, radiation, and prior cell therapy.
• Adequate organ function: hematologic, renal, hepatic, cardiac, and pulmonary function considered sufficient by protocoldefined laboratory and clinical thresholds.
• Negative pregnancy test for patients of childbearing potential and agreement to use effective contraception during the protocol-defined period.
• Written informed consent from parent/legal guardian and assent from the participant when appropriate.