A Study to Evaluate the Safety, Tolerance and Initial Efficacy of EGFRvIII CAR-T on Glioblastoma

NCT05802693 | Unknown Early Phase 1

• 1 other identifier: A03728
• Study Type: interventional
• Target: 22
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-center, open, dose-increasing study. For subjects with recurrent glioblastomaIt ,is estimated that about 22 subjects will be enrolled, The main purpose was to evaluate the safety and tolerance of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment of patients with recurrent glioblastoma.The secondary purpose is to preliminarily evaluate the anti-tumor activity of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment of patients with recurrent glioblastoma, and preliminarily evaluate the relationship between the clinical efficacy, safety and pharmacokinetics of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) preparation, as well as their correlation with tumor markers or other potential biomarkers. This clinical study is an open clinical study, including dose increasing stage and expansion stage. The main objective of the study was to observe the efficacy and safety of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) in the treatment of Glioblastoma (GBM) by local administration (Omaya capsule administration). The study will be divided into the following stages: screening stage, baseline stage, treatment stage, short-term follow-up and long-term follow-up stage.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Will assess dose limiting toxicity and all toxicities. Toxicity is the primary endpoint and will be assessed using the National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 . Rates and associated 95% Clopper and Pearson binomial confidence limits (95% confidence interval \[CI\]) will be estimated for participants' experiencing dose limiting toxicity (DLT). All toxicities and side effects will be summarized in tables by dose, time period, organ, and severity.

  Up to 15 years

• Dose-limiting toxicity (DLT)

  A toxicity that causes side effects that are serious enough to prevent an increase in dose or level of that treatment.

  Up to 28 days

Secondary Outcomes (11)

• T cell levels

  Up to 15 years

• Cytokine levels in PB

  Up to 15 years

• Disease response

  Up to 15 years

• Time to progression

  Up to 15 years

• Complete response (CR)

  Up to 15 years

Study Arms (1)

The dose increase phase of this study adopts a 3+3 half-step design

EXPERIMENTAL

The main research objective of active comparator is to observe the efficacy and safety of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) injected by local administration (Omaya capsule administration) in the treatment of Glioblastoma(GBM). Initial dose 22 × 10\^6 cells will adopt accelerated titration (ATD); 60 × 10\^6 cells，160 × 10\^6 cells and 220 × 10\^6 cells will use the BOIN method to increase the dose. The planned dose increase scheme is divided into accelerated titration stage (ATD) and BOIN stage

Drug: Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injection

Interventions

Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injection DRUG

Infusion of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) with Omaya capsule

Also known as: DCTY0801 Autologous T lymphocyte injection

The dose increase phase of this study adopts a 3+3 half-step design

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≤ age ≤ 70 years old, gender unlimited;
• Patients with recurrent glioblastoma confirmed by histology or cytology after surgery and treated with STUPP regimen (TMZ concurrent radiochemotherapy and adjuvant chemotherapy regimen);
• According to the response assessment in neuro-oncology(RANO) standard, tumor lesions with evaluable or measurable (measurable enhancement lesions are defined as enhancement lesions with clear boundary on CT or MRI, which can be developed on ≥ 2 axial films with a thickness of 5 mm, and the length and diameter of each other are more than 10 mm. If the scanning layer thickness is large, the minimum measurable lesion should be more than 2 times the layer thickness);
• Clinical pathology (immunohistochemical staining) confirmed the positive expression of EGFRvIII in the tumor;
• Sufficient peripheral blood can be obtained through vein, and there is no other contraindication for lymphocyte collection; The peripheral blood cells can be collected according to the requirements of cell preparation;
• KPS score ≥ 70 points;
• Estimated survival time ≥ 3 months;
• Subjects must give informed consent to the test before the test, and the written informed consent form shall be signed voluntarily by themselves (or their legal representatives).-

You may not qualify if:

• Those who have received radiotherapy after recurrence;
• They received immunosuppressive or glucocorticoid treatment within 2 weeks before enrollment;
• Those who receive live vaccine within 4 weeks before enrollment and/or plan to participate in the trial;
• He received other chemical drugs except lymphocyte clearance within 2 weeks before enrollment;
• Not recovered from the adverse events caused by previous anti-tumor treatment before enrollment (according to NCI-CTCAE v5.0, recovered to ≤ 1 level), excluding hair loss and sequelae;
• Previously received targeted drug therapy, cell therapy, gene therapy or other immunotherapy;
• Have received organ transplantation in the past;
• Those who are unable to perform brain MRI examination;
• Any of the following exceptions occurred in the laboratory inspection:
• Blood routine test: absolute neutrophil count (ANC) \< 1.5 × 10 ⁹/L, or platelet (PLT) \< 80 × 10 ⁹/L, or hemoglobin (HGB) \< 100 g/L;
• Coagulation function: prothrombin time (PT), or activated partial thromboplastin time (APTT), or INR \> 1.5 × ULN；
• Liver function: total bilirubin (TBIL)\>2 × ULN (upper limit of normal value), or alanine transferase (ALT), aspartate transferase (AST) \> 3 × ULN；
• Renal function: serum creatinine (Cr) ≥ 1.5 × ULN, or glomerular filtration rate (GFR) \< 60ml/min · 1.73m2;
• Subjects with active hepatitis B after treatment (HBsAg positive and HBV-DNA more than 1000 copies/ml (200 IU/ml) or higher than the lower detection limit, whichever is higher) are required to receive anti hepatitis B virus treatment during the study treatment; Active hepatitis C subjects (HCV antibody positive and HCV-RNA level higher than the lower limit of detection), human immunodeficiency virus or acquired immunodeficiency syndrome (HIV) related diseases. Note: Hepatocellular carcinoma(HCC) subjects with Hepatitis B virus(HBV) may be included in the study only after the researchers determine that their hepatitis is in a clinical stable state; No HCC subjects undergoing treatment are allowed to be enrolled with HCV;
• Cardiac ultrasound: left ventricular ejection fraction Left ventricular ejection fraction(LVEF)\<50%;

Sponsors & Collaborators

• Beijing Tsinghua Chang Gung Hospital: lead
• Beijing DCTY Biotech Co.,Ltd.: collaborator

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Yang Xuejun

CONTACT

13011329950; yxja03728@btch.edu.cn

Zuo Ran

CONTACT

15110273315; zr@taiyuanshengwu.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: April 6, 2023
• Study Start: November 15, 2023
• Primary Completion: November 14, 2025
• Study Completion: November 14, 2025
• Last Updated: August 25, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share