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

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

NCT ID: NCT05941156

Condition: Extranodal NK T Cell Lymphoma
NK-Cell Leukemia

Conditions: Official terms:
Lymphoma
Leukemia
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, Extranodal NK-T-Cell

Conditions: Keywords:
Anti-CD56 CAR-T

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: Anti-CD56 CAR T
Description: 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.
Arm group label: CAR-T Cell Infusion

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Patients or their legal guardians voluntarily participate and sign the informed consent; 2. Male or female patients aged 18-70 years (including 18 and 70 years); 3. The patient was diagnosed as NK/T cell lymphoma /NK cell leukemia by pathology or flow cytometry, and currently has no effective treatment options, such as relapse after chemotherapy or hematopoietic stem cell transplantation; Alternatively, patients voluntarily choose to administer anti-CD56-CAR T cells as salvage therapy. 4. The following two categories are included:(1)NK/T cell lymphoma;(2) NK cell leukemia. 5. Subject: (1)There was no remission or residual lesions after treatment, and HSCT (auto/allo-HSCT) was not suitable; (2)Relapse occurred after CR, and HSCT (auto/allo-HSCT) was not suitable; (3)Patients with high risk factors; (4)Relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy. 6. Measurable or evaluable lesions; 7. The patient's main tissues and organs function well: 1. Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L; 2. Renal function: creatinine < 220 μmol/L; 3. Lung function: indoor oxygen saturation ≥95%; 4. Cardiac function: left ventricular ejection fraction (LVEF) ≥40%. 8. The patients had not received any anti-cancer treatment such as chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) within the first 4 weeks of enrollment, and their previous treatment-related toxic reactions had recovered to ≤ grade 1 at the time of enrollment (except low toxicity such as hair loss); 9. The patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous infusion; 10. Patients with ECOG score ≤2 and expected survival time ≥3 months. Exclusion Criteria: 1. Women who are pregnant (urine/blood pregnancy test positive) or breastfeeding; 2. Men or women who have planned to become pregnant within the last 1 year; 3. The patients were not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment; 4. Patients had uncontrollable infectious diseases within 4 weeks prior to enrollment; 5. Active hepatitis B/C virus; 6. HIV-infected patients; 7. Suffering from a serious autoimmune disease or immunodeficiency disease; 8. The patient is allergic to antibodies, cytokines and other macromolecular biological drugs; 9. The patient had participated in other clinical trials within 6 weeks prior to enrollment; 10. Systemic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones); 11. Suffers from mental illness; 12. The patient has substance abuse/addiction; 13. According to the researchers' judgment, the patient had other conditions that were not suitable for inclusion.

Gender: All

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: The Affiliated Hospital of Xuzhou Medical University

Address:
City: Xuzhou
Zip: 221002
Country: China

Status: Recruiting

Contact:
Last name: Wei Sang, M.D., Ph.D

Phone: 13645207648
Email: xyfylbl515@xzhmu.edu.cn

Start date: May 1, 2023

Completion date: May 2026

Lead sponsor:
Agency: The Affiliated Hospital of Xuzhou Medical University
Agency class: Other

Source: The Affiliated Hospital of Xuzhou Medical University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05941156