EBV CAR-T Cells for Nasopharyngeal Carcinoma

Early Phase 1

Recruiting

• Conditions: Nasopharyngeal Carcinoma
• Interventions: Biological: CAR-T Cell Injection; Drug: Fludarabine; Drug: cyclophosphamide

• Registration Number: NCT05654077
• Lead Sponsor: The Affiliated Hospital of Xuzhou Medical University

Brief Summary

The aim of this study is to investigate the safety and preliminary efficacy of EBV CAR-T cells in the treatment of relapsed/refractory NPC

Detailed Description

The investigators designed a single-arm, open-label, "3+3" dose-escalation exploratory study. According to the subject and dose escalation test, the maximum dose or the best effective dose was determined to verify the safe and effective number of cells per body weight. A "3+3" dose escalation design was used to set three dose groups of gradually increasing CAR-T cells for therapeutic evaluation. The dose groups were 3.0×10\^6cells/kg, 9.0×10\^6cells/kg and 1.5×10\^7cells/kg, respectively. Cell reinfusion will take place on day 0 (d0) and each subject will be observed for at least 4 weeks after receiving cell reinfusion (DLT observation period).

Study Timeline

• Study Start: 2022-01-18
• Status Verified: 2022-12
• Study First Submitted: 2022-12-07
• Study First Submitted QC: 2022-12-07
• Last Update Submitted: 2022-12-15
• Study First Posted: 2022-12-16
• Last Update Posted: 2022-12-19
• Primary Completion: 2022-12-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• 1)Voluntarily sign written informed consent;
• 2)Age ≥18, ≤75 years old, male and female;
• 3 )Estimated survival ≥ 3 months;
• 4. ECOG physical fitness score was 0-2;
• 5. EBV positive nasopharyngeal carcinoma was diagnosed;
• 6. Positive target detection;
• 7. At least one measurable lesion according to RECIST V1.1 solid tumor evaluation criteria;
• 8. Patients with recurrent/metastatic nasopharyngeal carcinoma who had previously failed second-line or higher systemic therapy;
• 9. Monopheresis or venous blood collection venous access can be established, and there are no other contraindications for blood cell separation;
• 10. Full organ and bone marrow function,
• 11. Toxicity and side effects left by previous anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, etc.) ≤ grade 1 (CTCAE 5.0);
• 12. Fertile subjects (male or female) must use effective medical contraception during the study period and for 6 months after the end of administration. In female subjects of reproductive age, a negative pregnancy test should be performed within 72 h prior to the first dose.

Exclusion Criteria

• 1. There are active CNS metastases (except those stabilized by treatment);
• 2)HIV positive, HBsAg positive, HBV DNA copy number positive (quantitative test ≥1000cps/ mL), HCV antibody positive and HCV RNA positive;
• 3. Those with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation;
• 4. subjects with severe autoimmune diseases and long-term use of immunosuppressants;
• 5. Within 14 days prior to enrollment, there were active or uncontrollable infections requiring systemic treatment;
• 6. Any unstable systemic disease
• 7. Complicated with lung, brain, kidney and other important organ dysfunction;
• 8. Subjects have undergone major surgery or trauma in the 4 weeks prior to receiving cell therapy, or are expected to undergo major surgery during the study period;
• 9. Subjects received their last radiotherapy or anti-tumor therapy (chemotherapy, targeted therapy, or immunotherapy) within 4 weeks prior to receiving cell therapy;
• 10. The subject currently has or has had other malignancies that cannot be cured within 3 years, except cervical carcinoma in situ or basal cell carcinoma of the skin, and other malignancies with disease-free survival of more than 5 years;
• 11. T cells modified with chimeric antigen receptor (CAR T, TCR-T) within six months;
• 12. Combined graft versus host disease (GVHD);
• 13. Subjects who were receiving systemic steroids prior to screening and determined by the investigator to require long-term systemic steroid use during treatment (other than inhalation or topical use); And subjects who were treated with systemic steroids (except for inhalation or topical use) within 72 h prior to cell infusion;
• 14. A history of severe allergies or allergies;
• 15. Subjects requiring anticoagulant therapy;
• 16. Women who are pregnant or breast-feeding, or have a pregnancy plan within six months (for both men and women);
• 17. Researchers believe that there are other reasons not to include patients in the treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T Cell Injection	CAR-T Cell Injection	A total of 24 patients with recurrent or refractory NPC received a single intravenous infusion of CAR-T cells at doses of 3.0 × 10\^6cells/kg, 9.0 × 10\^6cells/kg, and 1.5 × 10\^7cells/kg, respectively, and were enrolled according to the conventional "3+3" dose escalation.
CAR-T Cell Injection	cyclophosphamide	A total of 24 patients with recurrent or refractory NPC received a single intravenous infusion of CAR-T cells at doses of 3.0 × 10\^6cells/kg, 9.0 × 10\^6cells/kg, and 1.5 × 10\^7cells/kg, respectively, and were enrolled according to the conventional "3+3" dose escalation.
CAR-T Cell Injection	Fludarabine	A total of 24 patients with recurrent or refractory NPC received a single intravenous infusion of CAR-T cells at doses of 3.0 × 10\^6cells/kg, 9.0 × 10\^6cells/kg, and 1.5 × 10\^7cells/kg, respectively, and were enrolled according to the conventional "3+3" dose escalation.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity（DLT）	From day 0 to day 28	Adverse events related to cell therapy were observed on 28 days after CAR-T cell injection , as specified in the protocol

Secondary Outcome Measures

Name	Time	Method
Tmax	12 months	Number of days of peak CAR-T cell expansion after administration
AUC(Day 0 to Day 28)	From day 0 to day 28	The area under the curve of CAR-T cells from day 0 to day 28 after administration was plotted by the visit time of CAR-T cells in peripheral blood
ORR	12 months	Proportion of patients who achieved pre-defined tumor volume change and maintained the minimum time limit.Imaging examination was performed after administration, and RECIST1.1 evaluation criteria was used for evaluation
Cmax	12 months	The amplification of CAR-T cells in peripheral blood peaked after administration
PFS	12 months	The time from the onset of leukocyte apheresis to the appearance of tumor progression or death
OS OS	12 months	The time between leukocyte apheresis and death from any cause

Trial Locations

Locations (1)

The Affiliated Hospital of Xuzhou Medical University; 🇨🇳 Xuzhou, Jiangsu, China