Autologous IC-Nine, CD30 CAR, and Constitutive IL7R Expressing EBVST for CD30 Lymphoma (ANCILE-30)

This is a Phase I study to evaluate the safety of autologous Epstein-Barr virus-specific T lymphocytes (EBVSTs) genetically modified to express a constitutively active interleukin-7 receptor (C7R) and a CD30-specific chimeric antigen receptor (CAR) (C7R.CD30-CAR-EBVSTs) in patients with relapsed or refractory CD30-positive lymphomas. The study will also evaluate the antitumor effect of C7R.CD30-CAR-EBVSTs, the expansion and persistence of the infused cells, and the association between immunological parameters, safety, and clinical response. Autologous CD30 CAR T cells have demonstrated clinical activity in patients with relapsed or refractory CD30-positive lymphomas but have shown limited persistence. Epstein-Barr virus-specific T lymphocytes (EBVSTs) have demonstrated long-term persistence following adoptive transfer. In this study, EBVSTs are used as the cellular platform to express both a CD30 CAR and a constitutively active IL7 receptor (C7R). The investigational cell product also provides a mechanism for rapid elimination of transduced cells if clinically indicated. Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of an autologous C7R.CD30-CAR-EBVST product. Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by intravenous infusion of C7R.CD30-CAR-EBVSTs. Participants who meet retreatment criteria, as defined in the protocol, may receive additional treatment cycles. Following treatment, participants will undergo scheduled follow-up evaluations including physical examinations, laboratory testing, and imaging studies to assess safety and disease status. Blood samples are collected at multiple time points after infusion to evaluate persistence of the infused cells. Tumor assessments are performed using imaging and, when clinically indicated, biopsy. Participants are followed longitudinally for up to 15 years after the most recent infusion.