EBV CAR-T Cells for Nasopharyngeal Carcinoma

NCT ID: NCT05654077

Last Updated: 2022-12-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-18
• Study Completion Date: 2025-12-30

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).

Conditions

Nasopharyngeal Carcinoma

Keywords

CAR-T; nasopharyngeal carcinoma; Recurrent/refractory nasopharyngeal carcinoma

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

CAR-T Cell Injection

Intervention Type: BIOLOGICAL

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

Fludarabine

Intervention Type: DRUG

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

cyclophosphamide

Intervention Type: DRUG

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

Interventions

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。

Intervention Type: BIOLOGICAL

Fludarabine

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

Intervention Type: DRUG

cyclophosphamide

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

Intervention Type: DRUG

Other Intervention Names

FLUDARA; Cytoxan

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangzhou Bioresette Biomedical Technology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

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

Yang Wu

Role: primary

Liantao Li

Role: backup

Other Identifiers

BR-EB-10

Identifier Type: -

Identifier Source: org_study_id