Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors

Summary

Patients may be considered if the cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study uses special immune system cells called AGAR T cells, a new experimental treatment.

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients.

Investigators have found from previous research that they can put a new gene (a tiny part of what makes-up DNA and carries your traits) into T cells that will make them recognize cancer cells and kill them. In the lab, investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GPC3. The antibody GPC3 recognizes a protein found solid tumors including pediatric liver cancers. This CAR is called GPC3-CAR. To make this CAR more effective, investigators also added a gene that includes IL15. IL15 is a protein that helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15 .This study will test T cells that investigators made (called genetic engineering) with GPC3-CAR and the IL15 (AGAR T cells) in patients with GPC3-positive solid tumors such as yours.

T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called Rimiducid. The investigators will insert the iCasp9 and IL15 together into the T cells using a virus that has been made for this study. The drug (Rimiducid) is an experimental drug that has been tested in humans with no bad side-effects. The investigators will use this drug to kill the T cells if necessary due to side effects.

This study will test T cells genetically engineered with a GPC3-CAR and IL15 (AGAR T cells) in patients with GPC3-positive solid tumors.

The AGAR T cells are an investigational product not approved by the Food and Drug Administration.

The purpose of this study is to find the biggest dose of AGAR T cells that is safe, to see how long they last in the body, to learn what the side effects are and to see if the AGAR T cells will help people with GPC3-positive solid tumors.

Conditions

• Liver Cancer
• Rhabdomyosarcoma
• Malignant Rhabdoid Tumor
• Liposarcoma
• Wilms Tumor
• Yolk Sac Tumor

Interventions

GENETIC

AGAR T cells

Four different dosing schedules will be evaluated. Three to six patients will be evaluated on each dosing schedule. The following dose levels will be evaluated: DL1: 3x10\^7/m2 DL2: 1x10\^8/m2 DL3: 3x10\^8/m2 DL4: 1x10\^9/m2 The doses are calculated according to the actual number of GPC3-CAR transduced T cells.

Sponsors & Collaborators

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

  collaborator OTHER

• National Institutes of Health (NIH)

  collaborator NIH

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• David Steffin, MD · Baylor College of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

1 Year

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-08-08

Primary Completion

2024-08-17

Completion

2040-08-26

FDA Drug

Yes

Countries

• United States

Study Locations