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

NCT04377932 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: H-47757 AGAR
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

15.GPC3-CAR T cells; GPC3; Glypican

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose Limiting Toxicity

  A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3-CAR T cells. Specifically those which are Grade 5; non-hematologic Grade 3-4 not returning to Grade 2 within 72 hours; Grade 2-4 allergic reaction; grade 4 hematologic toxicity that persists for 28 days or greater; all grade 4 CRS and neurologic toxicities and grade 3 CRS and neurologic toxicities that fail to return to Grade 1 within 7 days.

  4 weeks

Secondary Outcomes (2)

• Response Rate

  4 weeks

• Maximum Tolerated Dose (MTD) of Autologous Glypican-3 Specific Chimeric Antigen Expressing T Cells Co-expressing IL-15 Administered to Patients With GPC3-positive Solid Tumors.

  28 days

Study Arms (1)

AGAR T cells

EXPERIMENTAL

GPC3-CAR and the IL15 (AGAR T cells) will be administered to patients with GPC3-positive solid tumors.

Genetic: AGAR T cells

Interventions

AGAR T cells GENETIC

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.

Also known as: GPC3-CAR T cells

AGAR T cells

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of GPC3-positive\* solid tumors (as determined by immunohistochemistry with an extent score of \>=Grade 2 \[\>25% positive tumor cells\] and an intensity score of \>= 2 \[scale 0-4\]).
• Age ≥ 1 year and ≤ 21 years
• Life expectancy of ≥ 16 weeks
• Lansky or Karnofsky score ≥60%
• Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only
• Child-Pugh-Turcotte score \<7 (for patients with hepatocellular carcinoma only)
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

You may not qualify if:

• History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
• History of organ transplantation
• Known HIV positivity
• Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
• Actively progressing CNS metastases
• Treatment Eligibility
• Age ≥ 1 year and ≤ 21 years
• Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
• Lansky or Karnofsky score ≥ 60%
• Child-Pugh-Turcotte score \< 7 (for patients with hepatocellular carcinoma only)
• Adequate organ function:
• Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
• serum AST\< 5 times ULN
• total bilirubin \< 3 times ULN for age
• INR ≤1.7 (for patients with hepatocellular carcinoma only)

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Liver Neoplasms; Rhabdomyosarcoma; Rhabdoid Tumor; Liposarcoma; Wilms Tumor; Endodermal Sinus Tumor

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Complex and Mixed; Neoplasms, Adipose Tissue; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mesonephroma; Neoplasms, Germ Cell and Embryonal

Results Point of Contact

• Title: David Steffin, MD
• Organization: Baylor College of Medicine

dhsteffi@texaschildrens.org

(832) 824-4745

Study Officials

• David Steffin, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 7, 2020
• Study Start: August 8, 2021
• Primary Completion: August 17, 2024
• Study Completion (Estimated): August 26, 2040
• Last Updated: January 21, 2026
• Results First Posted: January 21, 2026

Record last verified: 2026-01

Locations

US (1)