Brain Tumor-Specific Immune Cells (IL13Ralpha2-CAR T Cells) for the Treatment of Leptomeningeal Glioblastoma, Ependymoma, or Medulloblastoma

NCT04661384 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 19497NCI-2020-06010P30CA033572
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial investigates the side effects of brain tumor-specific immune cells (IL13Ralpha2-CAR T cells) in treating patients with leptomeningeal disease from glioblastoma, ependymoma, or medulloblastoma. Immune cells are part of the immune system and help the body fight infections and other diseases. Immune cells can be engineered to destroy brain tumor cells in the laboratory. IL13Ralpha2-CAR T cells is brain tumor specific and can enter and express its genes in immune cells. Giving IL13Ralpha2-CAR T cells may better recognize and destroy brain tumor cells in patients with leptomeningeal disease from glioblastoma, ependymoma or medulloblastoma.

Conditions

Ependymoma; Glioblastoma; Medulloblastoma; Recurrent Metastatic Malignant Neoplasm in the Leptomeninges

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Will be assessed using the NCI's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 15 years

• Overall survival

  The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.

  At 3 months

Secondary Outcomes (11)

• CAR T cell detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)

  Up to 4 cycles (4 weeks)

• Endogenous T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)

  Up to 4 cycles (4 weeks)

• Cell phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)

  Up to 4 cycles (4 weeks)

• Cytokine levels in PB, TCF and CSF

  Up to 4 cycles (4 weeks)

• Disease response

  Up to 15 years

Study Arms (1)

Treatment (IL13Ralpha2-CAR T cells)

EXPERIMENTAL

Patients receive IL13Ralpha2-CAR T cells ICV over 5 minutes on day 1. Treatment repeats every 7 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Biological: IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes

Interventions

IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes BIOLOGICAL

Given ICV

Also known as: Autologous IL13(EQ)BBzeta/CD19t+ TCM-enriched T Cells

Treatment (IL13Ralpha2-CAR T cells)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Ependymoma; Glioblastoma; Medulloblastoma; Meningeal Carcinomatosis

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Neuroectodermal Tumors, Primitive; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Study Officials

• Lisa A Feldman

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: December 10, 2020
• Study Start: March 5, 2021
• Primary Completion (Estimated): January 12, 2027
• Study Completion (Estimated): January 12, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)