C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)

Summary

In this study, there are two treatment groups called Cohort 1 and Cohort 2. Cohort 1 is for patients with diffuse midline glioma, diffuse intrinsic pontine glioma, medulloblastoma, or another rare high-grade glioma that expresses GD2. Cohort 2 is for patients with a type of cancer called progressive diffuse intrinsic pontine glioma that expresses GD2.

Because there is no standard treatment at this time, patients are asked to volunteer in a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that help the body fight infection.

This research study combines two different ways of fighting cancer: antibodies and T cells. Both antibodies and T cells have been used to treat cancer patients. They have shown promise but have not been strong enough to cure most patients.

Researchers have found from previous research that they can put a new antibody gene into T cells that will make them recognize cancer cells and kill them. GD2 is a protein found on several different cancers. Researchers testing brain cancer cells found that many of these cancers also have GD2 on their surface.

In a study for neuroblastoma in children, a gene called a chimeric antigen receptor (CAR) was made from an antibody that recognizes GD2. This gene was put into the patients own T cells and given back to 11 patients. The cells did grow for a while but started to disappear from the blood after 2 weeks. The researchers think that if T cells are able to last longer they may have a better chance of killing tumor cells.

In this study, a new gene will be added to the GD2 T cells that can potentially cause the cells to live longer. T cells need substances called cytokines to survive. The gene C7R has been added that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time.

In other studies using T cells researchers found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and it will allow the T cells to expand and stay longer in the body and potentially kill cancer cells more effectively.

After treating 11 patients, the largest safe dose of GD2-CAR T cells given in the vein (IV) was determined. We are now combining an IV infusion with an infusion directly into the brain through the Ommaya reservoir or programmable VP shunt. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way.

Patients will now be assigned to Cohort 1 and 2 based on their tumor type.

The GD2.C7R T cells are an investigational product not approved by the FDA.

The purpose of this study is to combine infusions into the vein in the first treatment cycle with infusions directly into the cerebrospinal fluid (CSF) in the brain (intracerebroventricularly) through the ommaya reservoir or programmable VP shunt for infusions cycles 2-24. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way, and additionally to evaluate how long they can be detected in the blood and CSF and what affect they have on brain cancer.

Conditions

• Diffuse Intrinsic Pontine Glioma
• High Grade Glioma
• Embryonal Tumor
• Ependymal Tumor

Interventions

GENETIC

C7R-GD2.CART cells (IV and ICV infusion)

Dose levels administered are by IV infusion followed by ICV infusion. Cycle 1: 20 million cells/m2 delivered IV with lymphodepletion. Cycle 2 (and subsequent cycles): Dose level 1: 5 million cells ICV with lymphodepletion. Dose level 2: 10 million cells ICV with lymphodepletion. Dose level 3: 15 million cells ICV with lymphodepletion

GENETIC

C7R-GD2.CART cells (IV and ICV infusion)

Dose levels administered are by IV infusion followed by ICV infusion. Cycle 1: 20 million cells/m2 delivered IV with lymphodepletion. Cycle 2 (and subsequent cycles): Dose level 1: 5 million cells ICV with lymphodepletion. Dose level 2: 10 million cells ICV with lymphodepletion. Dose level 3: 15 million cells ICV with lymphodepletion

Sponsors & Collaborators

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• The Faris Foundation

  collaborator UNKNOWN

• ChadTough Defeat DIPG Foundation

  collaborator UNKNOWN

• Violet Foundation for Pediatric Brain Cancer

  collaborator UNKNOWN

• DIPG DMG Research Funding Alliance

  collaborator UNKNOWN

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Jasia Mahdi, MD · Baylor College of Medicine

• Bilal Omer, MD · Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Months

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-02-03

Primary Completion

2027-02-28

Completion

2041-02-28

FDA Drug

Yes

Countries

• United States

Study Locations