EBV CAR-T Cells for Nasopharyngeal Carcinoma

Sponsor

The Affiliated Hospital of Xuzhou Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05654077

Collaborator

Guangzhou Bioresette Biomedical Technology Co., Ltd. (Other)

Enrollment

Location

Arm

47.4

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Biological: CAR-T Cell Injection Drug: Fludarabine Drug: cyclophosphamide	Early Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

To Investigate the Safety and Preliminary Efficacy of EBV CAR-T Cells in the Treatment of Relapsed/Refractory EBV-positive Nasopharyngeal Carcinoma

Actual Study Start Date :

Jan 18, 2022

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: CAR-T Cell Injection intravenously once, and the dose group was 3.0 × 10^6cells/kg、9.0 × 10^6cells/kg、1.5 × 10^7cells/kg。 Drug: Fludarabine Fludarabine 25~30mg/m2/d was infused intravenously for 3 consecutive days. (- 5 days to - 3 days) Other Names: FLUDARA Drug: cyclophosphamide 250~350mg/m2/d cyclophosphamide was infused intravenously for 3 consecutive days. (- 5 days to - 3 days) Other Names: Cytoxan

Arm

Intervention/Treatment

Experimental: 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.

Biological: CAR-T Cell Injection

intravenously once, and the dose group was 3.0 × 10^6cells/kg、9.0 × 10^6cells/kg、1.5 × 10^7cells/kg。

Drug: Fludarabine

Fludarabine 25~30mg/m2/d was infused intravenously for 3 consecutive days. (- 5 days to - 3 days)

Other Names:

FLUDARA

Drug: cyclophosphamide

250~350mg/m2/d cyclophosphamide was infused intravenously for 3 consecutive days. (- 5 days to - 3 days)

Other Names:

Cytoxan

Outcome Measures

Primary Outcome Measures

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

Cmax [12 months]
The amplification of CAR-T cells in peripheral blood peaked after administration
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1)Voluntarily sign written informed consent;
2)Age ≥18, ≤75 years old, male and female;
3 )Estimated survival ≥ 3 months;
1. ECOG physical fitness score was 0-2;
1. EBV positive nasopharyngeal carcinoma was diagnosed;
1. Positive target detection;
1. At least one measurable lesion according to RECIST V1.1 solid tumor evaluation criteria;
1. Patients with recurrent/metastatic nasopharyngeal carcinoma who had previously failed second-line or higher systemic therapy;
1. Monopheresis or venous blood collection venous access can be established, and there are no other contraindications for blood cell separation;
1. Full organ and bone marrow function,
1. Toxicity and side effects left by previous anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, etc.) ≤ grade 1 (CTCAE 5.0);
1. 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;
1. Those with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation;
1. subjects with severe autoimmune diseases and long-term use of immunosuppressants;
1. Within 14 days prior to enrollment, there were active or uncontrollable infections requiring systemic treatment;
1. Any unstable systemic disease
1. Complicated with lung, brain, kidney and other important organ dysfunction;
1. 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;
1. Subjects received their last radiotherapy or anti-tumor therapy (chemotherapy, targeted therapy, or immunotherapy) within 4 weeks prior to receiving cell therapy;
1. 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;
1. T cells modified with chimeric antigen receptor (CAR T, TCR-T) within six months;
1. Combined graft versus host disease (GVHD);
1. 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;
1. A history of severe allergies or allergies;
1. Subjects requiring anticoagulant therapy;
1. Women who are pregnant or breast-feeding, or have a pregnancy plan within six months (for both men and women);
1. Researchers believe that there are other reasons not to include patients in the treatment.