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EBV CAR-T Cells for Nasopharyngeal Carcinoma

Primary Purpose

Nasopharyngeal Carcinoma

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
CAR-T Cell Injection
Fludarabine
cyclophosphamide
Sponsored by
The Affiliated Hospital of Xuzhou Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring CAR-T, nasopharyngeal carcinoma, Recurrent/refractory nasopharyngeal carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Affiliated Hospital of Xuzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T Cell Injection

Arm Description

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.

Outcomes

Primary Outcome Measures

Dose-limiting toxicity(DLT)
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
The amplification of CAR-T cells in peripheral blood peaked after administration
Tmax
Number of days of peak CAR-T cell expansion after administration
AUC(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
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
The time from the onset of leukocyte apheresis to the appearance of tumor progression or death
OS OS
The time between leukocyte apheresis and death from any cause

Full Information

First Posted
December 7, 2022
Last Updated
December 15, 2022
Sponsor
The Affiliated Hospital of Xuzhou Medical University
Collaborators
Guangzhou Bioresette Biomedical Technology Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05654077
Brief Title
EBV CAR-T Cells for Nasopharyngeal Carcinoma
Official Title
To Investigate the Safety and Preliminary Efficacy of EBV CAR-T Cells in the Treatment of Relapsed/Refractory EBV-positive Nasopharyngeal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 18, 2022 (Actual)
Primary Completion Date
December 30, 2022 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Affiliated Hospital of Xuzhou Medical University
Collaborators
Guangzhou Bioresette Biomedical Technology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Carcinoma
Keywords
CAR-T, nasopharyngeal carcinoma, Recurrent/refractory nasopharyngeal carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAR-T Cell Injection
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CAR-T Cell Injection
Intervention Description
intravenously once, and the dose group was 3.0 × 10^6cells/kg、9.0 × 10^6cells/kg、1.5 × 10^7cells/kg。
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
FLUDARA
Intervention Description
Fludarabine 25~30mg/m2/d was infused intravenously for 3 consecutive days. (- 5 days to - 3 days)
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
250~350mg/m2/d cyclophosphamide was infused intravenously for 3 consecutive days. (- 5 days to - 3 days)
Primary Outcome Measure Information:
Title
Dose-limiting toxicity(DLT)
Description
Adverse events related to cell therapy were observed on 28 days after CAR-T cell injection , as specified in the protocol
Time Frame
From day 0 to day 28
Secondary Outcome Measure Information:
Title
Cmax
Description
The amplification of CAR-T cells in peripheral blood peaked after administration
Time Frame
12 months
Title
Tmax
Description
Number of days of peak CAR-T cell expansion after administration
Time Frame
12 months
Title
AUC(Day 0 to Day 28)
Description
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
Time Frame
From day 0 to day 28
Title
ORR
Description
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
Time Frame
12 months
Title
PFS
Description
The time from the onset of leukocyte apheresis to the appearance of tumor progression or death
Time Frame
12 months
Title
OS OS
Description
The time between leukocyte apheresis and death from any cause
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
The Affiliated Hospital of Xuzhou Medical University
City
Xuzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Wu
Phone
+86-516-83355832
Email
claude134134@126.com
First Name & Middle Initial & Last Name & Degree
Liantao Li
Phone
+86-516-83355832
Email
liliantao@xzhmu.edu.cn

12. IPD Sharing Statement

Learn more about this trial

EBV CAR-T Cells for Nasopharyngeal Carcinoma

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