Clinical Study on the EBV CAR-T /TCR-T Cells in the Treatment of Nasopharyngeal Carcinoma

August 10, 2023 updated by: Ji Dongmei, Fudan University

Clinical Study on the Safety and Efficacy of EBV CAR-T /TCR-T Cells in the Treatment of Recurrent / Refractory EBV Positive Nasopharyngeal Carcinoma

This study was a single-arm, open-label, "3 + 3" dose-escalation Exploratory research. The patients were divided into two groups: EBV TCR-T-cell Group and EBV CAR-T-cell group. The EBV CAR-T-treated group received three progressively increasing dose levels (3.0 × 106 cells/kg, 9.0 × 106 cells/kg, 1.5 × 107 cells/kg) of EBV CAR-T-cell therapy; The EBV TCR-T-cell group received three progressively increasing doses (5.0 × 106 cells/kg, 1.5 × 107 cells/kg, 3.0 × 107 cells/kg) of EBV TCR-T-cell therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Each subject was observed for at least 4 weeks after cell reinfusion (DLT observation period) . A minimum of three participants should be included in each dose group, and two or more participants should not be included in each dose group at the same time, each subject should not be enrolled until the first 1 subject did not experience a grade 3 or higher adverse event (CTCAE5.0) related to the study drug during the DLT observation period. Three or six subjects were enrolled in each dose group, depending on the occurrence of DLT. If three subjects in one dose group did not experience DLT, three subjects were enrolled in the next higher dose group; if one of three subjects experienced DLT, three more subjects were enrolled in the dose group; Expanded to 6 subjects; if only 1 of the 6 subjects after amplification produced a DLT, then 3 subjects were enrolled into the next higher dose; If a DLT occurred in ≥2 of the 6 subjects after amplification, then the dose was specified to be higher than the MTD (MTD defined as the highest dose at which a DLT occurred in ≤1/6 subjects) , new subjects were included in the previous lower dose (tolerated dose) group until the lower dose group reached 6 subjects. If DLT occurred in ≤1/6 of the subjects, the lower dose group was defined as MTD or the best effective dose. A total of six subjects received the maximum tolerated dose. In the course of the study, the researcher can combine the safety and preliminary efficacy data of the enrolled subjects, and take the safety of the subjects and the maximum benefit of the disease as the premise, study treatment was performed at the maximum tolerated dose or other doses determined by the investigator.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Fudan University
        • Principal Investigator:
          • Dongmei Ji, Doctor
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Voluntary written informed consent;
  • Age ≥18 years old, ≤75 years old, male and female;
  • Expected survival ≥3 months;
  • The Eastern Cooperative Oncology Group (ECOG) physical fitness score was 0-2;
  • Ebv-positive nasopharyngeal carcinoma was diagnosed by in situ hybridization with Ebers (Eber-fish) .
  • Pathological Paraffin section testing (within 5 years before signing the informed consent form) ;
  • At least one measurable lesion according to RECIST v1.1 criteria for solid tumors;
  • Recurrent/metastatic nasopharyngeal carcinoma patients who had previously failed second-line or more systemic therapy;
  • An apheresis or venous access can be established and there are no other contraindications to blood cell isolation；
  • CTCAE 5.0 was lower than grade 1 in the side effects of previous anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, etc.)
  • During the study period and up to 6 months after the end of the administration, fertile subjects -LRB-both male and female) were required to use effective medical contraception. For women of reproductive age, a pregnancy test should be performed within 72 hours before the first dose, and the results were negative.

Exclusion Criteria:

  • Active central nervous system metastases (except those that are stable after treatment)；
  • HIV positive, HBsAg positive and HBV DNA copy number positive (quantitative detection ≥1000 CPS/ml) , HCV antibody positive and HCV RNA positive;
  • Patients with mental or psychological disorders who can not cooperate with the treatment and evaluation of the curative effect;
  • Subjects with severe autoimmune disease and long-term use of immunosuppressants;
  • Active or uncontrolled infection requiring systemic therapy was present within 14 days prior to enrollment；
  • Any unstable systemic disease;
  • Complicated with dysfunction of important organs such as lung, brain and kidney.
  • Subjects had undergone major surgery or severe trauma within 4 weeks before receiving cell therapy, or were expected to undergo major surgery during the study period.
  • Participants received their last dose of radiation or anti-tumor therapy within 4 weeks of receiving the cell therapy.
  • Participants had or had had other cancers that were incurable for up to 3 years, except for cervical cancer in situ or skin basal-cell carcinoma, and other cancers that had disease-free survival of more than 5 years.
  • Treated with Chimeric antigen receptor t-cell therapy within six months.
  • Graft-versus-host disease (GVHD)；
  • Subjects who were receiving systemic steroid therapy before screening and who required long-term systemic steroid therapy during treatment as determined by the investigator (with the exception of inhaled or topical use) ; And subjects treated with systemic steroids within 72 hours before cell reinfusion (except for inhalation or topical use) .
  • Severe allergies or a history of allergies;
  • Subjects requiring anticoagulant therapy;
  • Pregnant or lactating women, or a six-month pregnancy plan (for both men and women)；
  • Researchers believe there are other reasons not to include people in treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CAR-T
Target A positivity was assigned to CAR-T cell therapy.
Behavioral: PK Blood Collection
All subjects were subjected to PK blood sampling as prescribed by the protocol.
Drug: CAR
Target A positive subjects will receive CAR-T cell therapy.
Other Names:
  • CAR-T cell therapy
Experimental: TCR-T
Target A negative, Target B positive and Target C positive were assigned to TCR-T cell treatment group.
Behavioral: PK Blood Collection
All subjects were subjected to PK blood sampling as prescribed by the protocol.
Drug: TCR
Target A negative, Target B positive and Target C positive subjects will receive TCR-T cell therapy.
Other Names:
  • TCR -T cell therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicities
Time Frame: one year
Analysis based on clinical trial data of subjects
one year
MTD or the best effective dose
Time Frame: one year
Analysis based on clinical trial data of subjects
one year
Incidence of AE、SAE、AESI
Time Frame: one year
Analysis based on clinical trial data of subjects
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PK parameter：Cmax
Time Frame: one year
Analysis based on clinical trial data of subjects
one year
PK parameter：Tmax
Time Frame: one year
Analysis based on clinical trial data of subjects
one year
ORR
Time Frame: one year
Analysis based on clinical trial data of subjects
one year
DCR
Time Frame: one year
Analysis based on clinical trial data of subjects
one year
DOR
Time Frame: one year
Analysis based on clinical trial data of subjects
one year
PFS
Time Frame: one year
Analysis based on clinical trial data of subjects
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Collaborators

Guangzhou Bioresette Biomedical Technology Co., Ltd.
Chaosu Hu，Principal Investigator，Fudan University

Investigators

  • Principal Investigator: Dongmei Ji, Doctorate, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 28, 2022

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

October 1, 2030

Study Registration Dates

First Submitted

September 27, 2022

First Submitted That Met QC Criteria

October 19, 2022

First Posted (Actual)

October 20, 2022

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 10, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2207257-17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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