RECRUITING

Safety and Efficacy Study of TX103 CAR-T Cell Therapy for Recurrent or Progressive Grade 4 Glioma.

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase I, open-Label, single/multiple dose, dose-escalation study to evaluate the safety, tolerability and antitumor activity of anti-B7-H3 CAR-T cell injection (TX103) in subjects with recurrent or progressive Grade 4 Glioma.The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.

Official Title

A Phase I, Open-Label, Single/Multiple Dose, Dose-escalation Study to Evaluate the Safety, Tolerability and Antitumor Activity of TX103 CAR-T Cell Injection (TX103) in Subjects With Recurrent or Progressive Grade 4 Glioma.

Quick Facts

Study Start:2024-09-04

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06482905

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.

Ages Eligible for Study:18 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subjects must voluntarily participate in the study and sign a written informed consent document; subjects should be willing and able to follow and complete study procedures. 2. Male or female subjects aged 18 to 75 years (both inclusive). 3. Subject must have histologically diagnosed grade 4 glioma, such as glioblastoma, grade 4 astrocytoma, diffuse hemispheric glioma, according to 2021 WHO Classification of Tumors of the CNS. Subjects must have had experienced disease recurrence or progression\* after surgery combined with Stupp regimen (concurrent radiotherapy and temozolomide (TMZ) followed by adjuvant TMZ) and are not candidate for re-resection. For subjects harboring specific gene mutations, such as NTRK gene fusion or BRAF V600E mutation, they must have also progressed on corresponding mutation-directed therapies before enrollment. 4. Subjects with confirmed B7-H3 positive\* (≥30%) tumor expression by immunohistochemistry (IHC) in either primary or recurrent tumor tissue. 5. Subjects with KPS score of ≥60. 6. Subjects should have adequate venous access for collection of peripheral blood mononuclear cells (PBMCs). 7. Subjects with left ventricular ejection fraction (LVEF) ≥ 40% within one month prior to the first dose. 8. Subjects with oxygen saturation ≥95% under the resting state. 9. Subjects with adequate organ function, as indicated by laboratory test results that meet the following criteria: * Hematological function: Absolute neutrophil count (ANC) ≥1.5×109/L, hemoglobin (Hb) ≥90g/L, platelet count (PLT) ≥100×109/L, absolute lymphocytes count (ALC) ≥0.15×109/L. Blood transfusion, granulocyte (macrophage) colony stimulating factor, recombinant human erythropoietin, recombinant human thrombopoietin, platelet receptor agonist, recombinant human interleukin-11, and other supportive treatments are prohibited within 14 days before the test. * Liver function: Total bilirubin (TBIL) ≤ 1.5 × ULN, patients with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia, presenting as unconjugated bilirubin in the absence of evidence of hemolysis or liver pathology) Except for elevated erythrocytes; alanine aminotransferases (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. * Renal function: serum creatinine (Scr) ≤1.5×ULN. * Coagulation function (in the absence of anticoagulant therapy): prothrombin time (PT) or activated partial thromboplastin time (APTT) or international normalized ratio (INR) ≤ 1.5×ULN. * Female subjects of childbearing potential must have a negative serum pregnancy test at screening and if a positive urine test or a negative result cannot be confirmed by urine test. 10. Women of childbearing potential (which refer to women who have not been surgically sterilized and pre-menopausal women) should use highly effective and reliable method of contraception (refer to Section 5.3 for contraception method) from the start of the study until 6 months after the last dose of the study drug; sexually active male subjects, if no vas deferens for ligation, consent must be given to the use of highly effective and reliable method of contraception from the start of the study until 6 months after the last dose of the study drug.	1. Pregnant or breastfeeding female subjects. 2. Subjects with viral infection during the screening period: * Serum HIV antibody positive, treponema pallidum serology positive; OR * Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV DNA test value exceeds the normal range; OR * Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive. 3. Medical history and concomitant diseases: * Subjects who have received carmustine extended-release implantation surgery within 6 months; * Subjects with known or suspected active autoimmune diseases, including but not limited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.; * Subjects who are receiving systemic immunosuppressive agents or subjects who need to use immunosuppressive agents for a long-time during treatment, except for intermittent topical, inhaled, or intranasal glucocorticoid therapy; * Subjects with uncontrolled mental disorders, or who, in the Investigator's opinion, have a medical history or a history of mental states that may increase the risks associated with study participation or study drug administration, or that may interfere with the results; * The toxicity and side effects caused by previous treatment have not recovered to ≤ grade 1 (per CTCAE 5.0); except for alopecia and other tolerable events judged by the Investigator; * Subjects who have participated in other interventional clinical studies within the past 1 month; * Subjects who have previously received CAR-T cell therapy or other gene therapy\; Subjects with any serious or poorly controlled disease that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or affect the subject's ability to receive study drug, including but not limited to cardiovascular and cerebrovascular diseases, renal insufficiency, pulmonary embolism, coagulopathy or requiring long-term anticoagulant therapy, active infection or uncontrollable infection requiring long-term systemic treatment; * Subjects with other malignant tumors in the past 3 years or at present, except for non-melanoma skin cancer, carcinoma in situ (such as cervix, bladder and breast cancer).

Inclusion Criteria

Exclusion Criteria

1. Subjects must voluntarily participate in the study and sign a written informed consent document; subjects should be willing and able to follow and complete study procedures.
2. Male or female subjects aged 18 to 75 years (both inclusive).
3. Subject must have histologically diagnosed grade 4 glioma, such as glioblastoma, grade 4 astrocytoma, diffuse hemispheric glioma, according to 2021 WHO Classification of Tumors of the CNS. Subjects must have had experienced disease recurrence or progression\* after surgery combined with Stupp regimen (concurrent radiotherapy and temozolomide (TMZ) followed by adjuvant TMZ) and are not candidate for re-resection. For subjects harboring specific gene mutations, such as NTRK gene fusion or BRAF V600E mutation, they must have also progressed on corresponding mutation-directed therapies before enrollment.
4. Subjects with confirmed B7-H3 positive\* (≥30%) tumor expression by immunohistochemistry (IHC) in either primary or recurrent tumor tissue.
5. Subjects with KPS score of ≥60.
6. Subjects should have adequate venous access for collection of peripheral blood mononuclear cells (PBMCs).
7. Subjects with left ventricular ejection fraction (LVEF) ≥ 40% within one month prior to the first dose.
8. Subjects with oxygen saturation ≥95% under the resting state.
9. Subjects with adequate organ function, as indicated by laboratory test results that meet the following criteria:
* Hematological function: Absolute neutrophil count (ANC) ≥1.5×109/L, hemoglobin (Hb) ≥90g/L, platelet count (PLT) ≥100×109/L, absolute lymphocytes count (ALC) ≥0.15×109/L. Blood transfusion, granulocyte (macrophage) colony stimulating factor, recombinant human erythropoietin, recombinant human thrombopoietin, platelet receptor agonist, recombinant human interleukin-11, and other supportive treatments are prohibited within 14 days before the test.
* Liver function: Total bilirubin (TBIL) ≤ 1.5 × ULN, patients with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia, presenting as unconjugated bilirubin in the absence of evidence of hemolysis or liver pathology) Except for elevated erythrocytes; alanine aminotransferases (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN.
* Renal function: serum creatinine (Scr) ≤1.5×ULN.
* Coagulation function (in the absence of anticoagulant therapy): prothrombin time (PT) or activated partial thromboplastin time (APTT) or international normalized ratio (INR) ≤ 1.5×ULN.
* Female subjects of childbearing potential must have a negative serum pregnancy test at screening and if a positive urine test or a negative result cannot be confirmed by urine test.
10. Women of childbearing potential (which refer to women who have not been surgically sterilized and pre-menopausal women) should use highly effective and reliable method of contraception (refer to Section 5.3 for contraception method) from the start of the study until 6 months after the last dose of the study drug; sexually active male subjects, if no vas deferens for ligation, consent must be given to the use of highly effective and reliable method of contraception from the start of the study until 6 months after the last dose of the study drug.

1. Pregnant or breastfeeding female subjects.
2. Subjects with viral infection during the screening period:
* Serum HIV antibody positive, treponema pallidum serology positive; OR
* Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV DNA test value exceeds the normal range; OR
* Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive.
3. Medical history and concomitant diseases:
* Subjects who have received carmustine extended-release implantation surgery within 6 months;
* Subjects with known or suspected active autoimmune diseases, including but not limited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.;
* Subjects who are receiving systemic immunosuppressive agents or subjects who need to use immunosuppressive agents for a long-time during treatment, except for intermittent topical, inhaled, or intranasal glucocorticoid therapy;
* Subjects with uncontrolled mental disorders, or who, in the Investigator's opinion, have a medical history or a history of mental states that may increase the risks associated with study participation or study drug administration, or that may interfere with the results;
* The toxicity and side effects caused by previous treatment have not recovered to ≤ grade 1 (per CTCAE 5.0); except for alopecia and other tolerable events judged by the Investigator;
* Subjects who have participated in other interventional clinical studies within the past 1 month;
* Subjects who have previously received CAR-T cell therapy or other gene therapy\*;
* Subjects with any serious or poorly controlled disease that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or affect the subject's ability to receive study drug, including but not limited to cardiovascular and cerebrovascular diseases, renal insufficiency, pulmonary embolism, coagulopathy or requiring long-term anticoagulant therapy, active infection or uncontrollable infection requiring long-term systemic treatment;
* Subjects with other malignant tumors in the past 3 years or at present, except for non-melanoma skin cancer, carcinoma in situ (such as cervix, bladder and breast cancer).

Contacts and Locations

Study Contact

Rui Feng, MD

CONTACT

+(86)13509312934

fengrui@tcelltech.com

Xianzhen Chen, MM

CONTACT

+(86)18649725652

chenxianzhen@tcelltech.com

Principal Investigator

Gangxiong Huang, MD

STUDY_DIRECTOR

Tcelltech Inc.

Study Locations (Sites)

Mayo Clinic in Arizona

Phoenix, Arizona, 85054

United States

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

United States

Collaborators and Investigators

Sponsor: Tcelltech Inc.

Gangxiong Huang, MD, STUDY_DIRECTOR, Tcelltech Inc.

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 Registration Dates

Study Start Date2024-09-04

Study Completion Date2027-06

Study Record Updates

Study Start Date2024-09-04

Study Completion Date2027-06

Terms related to this study

Additional Relevant MeSH Terms

High-grade Glioma
WHO Grade Ⅳ Glioma