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

NCT ID: NCT05941156

Last Updated: 2023-07-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-01
• Study Completion Date: 2026-05-31

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR-T Cell Infusion

Pretreatment was initiated at -5 days prior to CAR T cell reinfusion, and CAR T cell therapy was performed 2 days after completion of chemotherapy. All patients were pretreated with FC regimen, fludarabine: 30mg/m2×3 days, cyclophosphamide: 750mg/m2×1 day. Anti CD56-CAR T cells were transfused back 2 days after chemotherapy. The freeze-thawed cell product solution is injected back into the body as soon as the patient can accept it. The patient's vital signs should be closely monitored throughout the infusion, and oxygen saturation should be measured at 15-minute intervals before, at the end of, and after infusion, and continue until the patient is stable. 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.

Group Type: EXPERIMENTAL

Anti-CD56 CAR T

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Hospital of Xuzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Wei Sang, M.D., Ph.D

Role: primary

xyfylbl515@xzhmu.edu.cn

13645207648

Other Identifiers

XYFY2023-KL123-01

Identifier Type: -

Identifier Source: org_study_id