NCT05941156

Clinical Study of Anti-CD56-CAR-T in the Treatment of Relapsed/Refractory NK/T Cell Lymphoma /NK Cell Leukemia

Single-center, Open, One-arm Clinical Study of the Safety and Efficacy of Anti-CD56-CAR T Therapy in Relapsed Refractory NK/T Cell Lymphoma /NK Cell Leukemia

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: The Affiliated Hospital of Xuzhou Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

To evaluate the safety and efficacy of anti-CD56-CAR T in the treatment of relapsed refractory NK/T cell lymphoma /NK cell leukemia

Detailed description

Extranodal NK/TCL is an aggressive disease with a poor prognosis and a 5-year survival rate of less than 50%. In the absence of effective treatment, median survival for advanced disease is only 6-12 months. A retrospective review of the International Peripheral T-Cell Lymphoma Project recently reported that the median overall survival of NK/TCL was 7.8 months, corresponding to the worst survival of all T-cell lymphoma entities. Therefore, despite good results in the combination of chemoracal-chemotherapy strategies, autologous bone marrow transplantation, and L-asparagase in the treatment of recurrent cases, NK/TCL remains difficult to cure, and the need for alternative therapeutic strategies has prompted researchers to explore new molecular targets. Nerve cell adhesion molecule 1 (NCAM-1) -CD56 is a member of the immunoglobulin superfamily and is a biomarker of nerve cell adhesion molecule and NK cell. CD56 is highly expressed in NK/T cell lymphomas, skeletal muscle tumors, and malignancies with neurological or neuroendocrine differentiation. CD56-CAR T cells can kill CD56+ neuroblastoma, glioma, and SCLC tumor cells in vitro coculture, and CD56R-CAR+T cells can inhibit tumor growth in vivo when tested against CD56+ human neuroblastoma xenogeneic and SCLC models. CD56-CAR T cells have also been reported as a safe and effective treatment for refractory/relapsing rhabdomyosarcoma. This indicates that CD56 CAR has a wide clinical application prospect and strong potential therapeutic value as a new CAR T target. CD56 CAR T cells constructed by our laboratory can produce more precise killing effect on tumor cells by converting the immune checkpoint PD-1 signal. The results showed that CD56 CAR T cells could be prepared effectively and kill NK/ T-cell lymphoma cell line SNK-6 in vitro. Compared with traditional second-generation CAR T cells, CD56-CAR T cells prepared in our laboratory showed better killing effect on SNK-6 cells in vitro. At present, no clinical studies on CD56 CAR T therapy for NK/T cell lymphoma have been reported. Therefore, in this study, CD56 CAR T was used to treat relapsed and refractory NK/T cell lymphoma /NK cell leukemia to observe its safety and efficacy.

Conditions

• Extranodal NK T Cell Lymphoma
• NK-Cell Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Anti-CD56 CAR T	CAR T cells were pretreated at -5 days before retransfusion (FC regimen: fludarabine: 30mg/m2×3 days, cyclophosphamide: 750mg/m2×1 day). Anti CD56-CAR T cells were transfused back to the patient 2 days after the end of chemotherapy. 30 to 60 minutes before CAR T cell infusion, patients were given 325 to 650 mg of acetaminophen orally to prevent infusion-related reactions; If fever occurred on the day of CAR T cell infusion, lasted less than 24 hours, and had no other toxicity, it was attributed to the infusion T cell response.

Timeline

• Start date: 2023-05-01
• Primary completion: 2026-05-01
• Completion: 2026-05-01
• First posted: 2023-07-12
• Last updated: 2023-07-12

Locations

1 site across 1 country: China