Using engineered immune cells to treat brain tumors in the leptomeninges

A Phase 1 Study to Evaluate IL13Rα2-Targeted Chimeric Antigen Receptor (CAR) T Cells for Adult Patients With Leptomeningeal Glioblastoma, Ependymoma or Medulloblastoma

This study is testing if specially designed immune cells can safely target and kill brain tumor cells in patients with leptomeningeal disease caused by certain types of brain cancer.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: City of Hope Medical Center (other)
• Drugs / interventions: tocilizumab, CAR T, chemotherapy, radiation
• Locations: 1 site (Duarte, California)
• Trial ID: NCT04661384 on ClinicalTrials.gov

What this trial studies

This phase I trial evaluates the safety and feasibility of IL13Ralpha2-CAR T cells, which are engineered immune cells designed to target and destroy brain tumor cells, in patients with leptomeningeal disease from glioblastoma, ependymoma, or medulloblastoma. Participants will receive these CAR T cells through intracerebroventricular delivery as an adjuvant therapy. The study aims to assess the activity of these cells based on survival rates and to analyze their persistence and effects on tumor response. Secondary objectives include monitoring cytokine levels and evaluating disease progression over a three-month period.

Who should consider this trial

Good fit: Ideal candidates include individuals with confirmed leptomeningeal metastases from glioblastoma, ependymoma, or medulloblastoma who meet specific health criteria.

Not a fit: Patients without IL13Ralpha2+ tumor expression or those with a Karnofsky performance status below 60 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel and effective option for patients with difficult-to-treat brain tumors in the leptomeninges.

How similar studies have performed: While CAR T cell therapy has shown promise in other cancers, this specific application for leptomeningeal brain tumors is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Participant has verified leptomeningeal metastases
* Participant must have a Karnofsky performance status (KPS) \>= 60
* Participant must have a life expectancy of \>= 8 weeks
* If participant has a ventriculoperitoneal shunt, the valve must be programmable, and must be able to tolerate their shunts being turned off for 48 hours
* The effects of IL13Ralpha2-CAR T cells on a developing fetus are unknown. For this reason, women of child-bearing potential must have negative serum pregnancy test and agree to use a reliable form of birth control prior to study entry and for at least two months following study treatment. Male research participants must agree to use a reliable form of birth control and not donate sperm during the study and for at least two months following study treatment
* Participant has a histologically confirmed IL13Ralpha2+ tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \>= 50)
* Participant must have the ability to understand and the willingness to sign a written informed consent
* No known contraindications to leukapheresis, steroids, or tocilizumab

Exclusion Criteria:

* Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
* Research participant requires dialysis
* Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
* Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase 1 study. A legal guardian may substitute for the research participant
* Participant is unwilling to stop treatment with chemotherapy or endocrine therapy and/or radiation one week prior and during the first 4 cycles of the IL13Ralpha2-CAR T cell study
* Shunted participants either have a non-programmable shunt valve, or cannot tolerate their shunts being turned off for 48 hours
* Participant has a coagulopathy or bleeding disorder or cannot safely discontinue anticoagulation prior to placement of a Rickham reservoir
* Participant has a chronic or active viral infection of the central nervous system (CNS)
* Participant has any uncontrolled illness, including ongoing or active infection; participant has known active hepatitis B or C infection; participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
* Participant is human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of signing the main informed consent
* Participant has an autoimmune disease
* Participant has another active malignancy
* Participant is unable to undergo a brain magnetic resonance imaging (MRI)
* Participant is pregnant or breast feeding. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IL13Ralpha2-CAR T cells, breastfeeding should be discontinued if the mother wants to participate in this study
* 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)

Where this trial is running

Duarte, California

• City of Hope Medical Center — Duarte, California, United States (RECRUITING)

Study contacts

• Principal investigator: Lisa A Feldman — City of Hope Medical Center

Conditions: Ependymoma, Glioblastoma, Medulloblastoma, Recurrent Metastatic Malignant Neoplasm in the Leptomeninges