RECRUITING

Intracranial Genetically Modified Immune Cells (TGFβR2KO/IL13Rα2 CAR T-Cells) for the Treatment of Recurrent or Progressive Glioblastoma or Grade 3 or 4 IDH-Mutant Astrocytoma

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Conditions

Recurrent Astrocytoma, IDH-Mutant, Grade 3Recurrent Astrocytoma, IDH-Mutant, Grade 4Recurrent Glioblastoma

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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 phase I trial tests the safety, side effects and best dose of TGFβR2KO/IL13Rα2 chimeric antigen receptor (CAR) T-cells given within the skull (intracranial) in treating patients with glioblastoma or IDH-mutant grade 3 or 4 astrocytoma that has come back after a period of improvement (recurrent) or that is growing, spreading, or getting worse (progressive). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. When the cells are taken from the patient's own blood, it is known as autologous. Then the gene for special receptors that bind to a certain proteins on the patient's tumor cells are added to the T cells in the laboratory. The special receptors are called CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain tumors. Giving TGFβR2KO/IL13Rα2 CAR T cells may be safe, tolerable, and/or effective in treating patients with recurrent or progressive glioblastoma or grade 3 or 4 IDH-mutant astrocytoma.

Official Title

A Phase 1 Trial to Evaluate the Safety of IL13Rα2-Targeting Chimeric Antigen Receptor (CAR) T Cells With CRISPR Knockout of TGFβR2 in Patients With Recurrent or Progressive High-Grade Glioma (HGG)

Quick Facts

Study Start:2026-01-02
Study Completion:2030-02-05
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06815029

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
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Documented informed consent of the participant and/or legally authorized representative
  2. * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with surgery/Rickham placement and CAR T cell infusion only after the translated main consent form is signed
  3. * Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval
  4. * Age: ≥ 18 years
  5. * Karnofsky performance status (KPS) ≥ 70%, Eastern Cooperative Oncology Group (ECOG) ≤ 2
  6. * Life expectancy ≥ 4 weeks
  7. * If the participant has a shunt, they must be informed of the following:
  8. * If the shunt is not programmable, the participant must be willing to have a programmable shunt placed prior to CAR T cell infusion, and
  9. * If the shunt is programmable, in order to proceed to the treatment portion of the study, the participant must be able to tolerate their shunt being functionally closed for at least 2 hours
  10. * Participant has a prior histologically-confirmed diagnosis of a grade 3 or 4 IDH-mutant astrocytoma or glioblastoma, or has a prior histologically-confirmed diagnosis of a grade 2 or 3 astrocytoma and now has radiographic progression consistent with grade 3 or 4 IDH-mutant astrocytoma
  11. * Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy, and ≥ 12 weeks after completion of front-line radiation therapy
  12. * COH clinical pathology confirms IL13Rα2+ tumor expression by immunohistochemistry (H-score ≥ 80)
  13. * No known contraindications to leukapheresis, steroids, or tocilizumab
  14. * White blood cell (WBC) \> 2000 /dl (or absolute neutrophil count \[ANC\] ≥ 1,000/mm\^3) (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  15. * Platelets ≥ 75,000/mm\^3 (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  16. * Hemoglobin ≥ 8g/dl (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  17. * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  18. * Aspartate aminotransferase (AST) ≤ 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  19. * Alanine aminotransferase (ALT) ≤ 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  20. * Serum creatinine ≤ 1.6 mg/dL (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  21. * Oxygen (O2) saturation ≥ 95% on room air (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  22. * Seronegative for HIV antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  23. * Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (to be performed within 14 days prior to leukapheresis unless otherwise stated)
  24. * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  25. * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
  26. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  1. * Owing to higher frequency of wound-related complications, participants who require active bevacizumab therapy at the time of enrollment are excluded
  2. * Participant has not yet recovered from toxicities of prior therapy
  3. * Uncontrolled seizure activity and/or clinically evident progressive encephalopathy
  4. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  5. * Clinically significant uncontrolled illness
  6. * Active autoimmune disease requiring systemic immunosuppressive therapy
  7. * Active infection requiring intravenous (IV) antibiotics (e.g., minor scalp infection is not an exclusion)
  8. * Known history of human immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  9. * Other active malignancy. Note: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  10. * Females only: Pregnant or breastfeeding
  11. * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  12. * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Principal Investigator

Behnam Badie
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Behnam Badie, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

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 Date2026-01-02
Study Completion Date2030-02-05

Study Record Updates

Study Start Date2026-01-02
Study Completion Date2030-02-05

Terms related to this study

Additional Relevant MeSH Terms

  • Recurrent Astrocytoma, IDH-Mutant, Grade 3
  • Recurrent Astrocytoma, IDH-Mutant, Grade 4
  • Recurrent Glioblastoma