EBV-specific CTLs for Neuroblastoma
(NESTLES Trial)

Recruiting in Palo Alto (17 mi)

Overseen byAndras A Heczey, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Baylor College of Medicine

No Placebo Group

Trial Summary

What is the purpose of this trial?

Patients have high-risk neuroblastoma, a form of cancer typically found in children. The patients previously participated in a gene transfer research study using special immune cells. This research study combines two different ways of fighting disease, antibodies and T cells. Antibodies are types of proteins that protect the body from bacterial and other infections. T cells, also called cytotoxic T lymphocytes or CTLs, are special infection-fighting blood cells that can kill some tumor cells. Both antibodies and T cells have been used to treat patients with cancers and while they have shown promise, they have not been strong enough to cure most patients. The antibody used in this study is called 14g2a. This antibody sticks to neuroblastoma cells because of a substance on the outside of these cells called GD2. 14g2a and other antibodies that bind to GD2 have been used to treat people with neuroblastoma. For this study 14g2a has been changed so that instead of floating free in the blood, it is now joined to T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. T lymphocytes or CTLs can kill tumor cells but there normally are not enough of them to kill all tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the patient. Sometimes an antibody or chimeric receptor is attached to these T cells to help them bind to tumor cells. These chimeric receptor-T cells seem to kill some of the tumor, but they don't last very long in the body and so the tumor eventually comes back. We have found that T cells that are also trained to recognize the virus that causes infectious mononucleosis, Epstein Barr Virus (EBV), can stay in the blood stream for many years. By joining the 14g2a antibody to the CTLs that recognize EBV, we believe we will make a cell that can last a long time in the body (because they are EBV-specific) and recognize and kill neuroblastoma cells (because an antibody that can recognize these cells has been placed on their surface). Patients received treatment with the immune cells described above. They may want to receive an additional dose of these cells. This is being offered as an option because their neuroblastoma has returned and they have enough cells remaining to provide the patients with an additional dose. These 14g2a antibody CTLs are an investigational product not approved by the Food and Drug Administration.

Research Team

Andras A Heczey, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for children with high-risk neuroblastoma who have relapsed or persistent disease after initial therapy. They must not require oxygen (>90% on room air), expect to live at least 12 weeks, and recovered from previous chemotherapy effects. No investigational agents or tumor vaccines should have been received in the last 6 weeks. Participants need normal blood counts, liver and kidney function, no severe heart/lung issues, a decent performance score (Karnofsky/Lansky >60%), and specific immune cells from a prior study.

Inclusion Criteria

My neuroblastoma is high risk and has either come back or didn't fully respond to initial treatment.

Patients must have AST less than 5 times the upper limit of normal

Patient may not have an oxygen requirement as defined by pulse oximetry of > 90% on room air

See 16 more

Exclusion Criteria

Patients not meeting eligibility criteria

Treatment Details

Interventions

EBV Specific CTLs (Virus Therapy)
GD-2 Specific Chimeric T Cell Receptors (CAR T-cell Therapy)

Trial OverviewThe trial tests modified immune cells (CTLs) that are trained to fight both neuroblastoma cancer cells and EBV virus by using an antibody called 14g2a attached to them. These 'chimeric receptor-T cells' aim to last longer in the body and effectively target cancer cells. Patients may receive an additional dose of these CTLs if their cancer has returned.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: EBV specific CTLs w/out lymphodepletionExperimental Treatment1 Intervention

Escalating doses of 14g2a.zeta chimeric receptor transduced autologous EBV specific cytotoxic T-lymphocytes (EBV-CTL) and 14g2a.zeta transduced autologous peripheral blood T-cells administered to patients with Neuroblastoma.