CAR T Cell Therapy for Pediatric Brain Cancer

Palo Alto (17 mi)

Age: < 65

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Seattle Children's Hospital

No Placebo Group

Trial Summary

What is the purpose of this trial?This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4 and CD8 T cells lentivirally transduced to express a HER2-specific chimeric antigen receptor (CAR) and EGFRt, delivered by an indwelling catheter in the tumor resection cavity or ventricular system in children and young adults with recurrent or refractory HER2-positive CNS tumors. A child or young adult with a refractory or recurrent CNS tumor will have their tumor tested for HER2 expression by immunohistochemistry (IHC) at their home institution or at Seattle Children's Hospital. If the tumor is HER2 positive and the patient meets all other eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meets none of the exclusion criteria, then they can be apheresed, meaning T cells will be collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets HER2-expressing tumor cells. The patient's newly engineered T cells will then be administered via the indwelling CNS catheter for two courses. In the first course they will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Following the two courses, patient's will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving additional courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available. The hypothesis is that an adequate amount of HER2-specific CAR T cells can be manufactured to complete two courses of treatment with three doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that HER-specific CAR T cells safely can be administered through an indwelling CNS catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study safely can be delivered directly into the brain via indwelling catheter. Secondary aims of the study will include to evaluate CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple time points are available, also evaluate the degree of HER2 expression at diagnosis versus at recurrence.

Eligibility Criteria

This trial is for children and young adults aged 1 to 26 with recurrent or refractory HER2-positive CNS tumors who have no standard therapy options left. They must have a CNS catheter in place, a life expectancy of at least 8 weeks, recovered from previous treatments, stable or decreasing steroid use, good organ function and lab values, not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

My brain tumor is HER2 positive.

I can undergo apheresis or already have an apheresis product ready for use.

It has been over a week since my last chemotherapy or biologic treatment.

It's been over 30 days or 3 half-lives since my last antibody therapy.

It has been over 30 days since my last cell infusion.

I can care for myself but may need occasional help.

My brain or spinal cord cancer has come back or isn't responding to treatment, and there's no standard treatment left.

I am between 1 and 26 years old.

Exclusion Criteria

I have been diagnosed with a specific brain tumor known as DIPG.

I have severe heart issues or irregular heartbeats needing treatment.

I am showing signs of a possible herniation.

I have cancer in parts of my body other than my brain.

I am currently fighting a severe infection.

I have a condition that affects my immune system or bone marrow.

Treatment Details

The study tests HER2-specific CAR T cell therapy delivered through an indwelling CNS catheter over two courses. Each course involves weekly doses for three weeks followed by one week off. The treatment aims to allow engineered T cells to directly interact with tumor cells in the brain.

2Treatment groups

Experimental Treatment

Group I: ARM B (Ventricular System Infusion)Experimental Treatment1 Intervention

patients with either infratentorial tumors or leptomeningeal tumors for which the CAR T cells will be delivered into the fourth ventricle or lateral ventricle, respectively Intervention: HER2-specific chimeric antigen receptor (CAR) T cell

Group II: ARM A (Tumor Cavity Infusion)Experimental Treatment1 Intervention

patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity Intervention: HER2-specific chimeric antigen receptor (CAR) T cell