Modified Immune Cells (GPC3-CAR T cells) for the Treatment of Relapsed or Refractory Pediatric Solid Tumors

Status: Active

Description

This phase I trial studies the side effects and best dose of GPC3-CAR T cells in treating pediatric patients with solid tumors that have come back or do not respond to treatment. This 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. In the laboratory, new genes called chimeric antigen receptors (CARs) are made from an antibody called GC33 that recognizes glypican-3, a protein found on solid tumors (GPC3-CAR). T cells genetically engineered with a GPC3-CAR may recognize cancer cells and kill them.

Eligibility Criteria

Inclusion Criteria

  • PROCUREMENT: Relapsed or refractory GPC3-positive solid tumors. * GPC3 expression will be evaluated by standard immunohistochemistry (IHC). A tumor is considered GPC3 positive, when the staining is grade 2 (> 25% positive tumor cells) or above with an intensity score of 2 or above on a scale of 0 to 4.
  • PROCUREMENT: Age >= 1 year and =< 21 years (NOTE: The first three [3] patients on this study will be between the ages of 15-21 years).
  • PROCUREMENT: Lansky or Karnofsky score >= 60%.
  • PROCUREMENT: Life expectancy >= 16 weeks.
  • PROCUREMENT: Child-Pugh-Turcotte score < 7 (for patients with hepatocellular carcinoma only).
  • PROCUREMENT: Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
  • TREATMENT: Age >= 1 year and =< 21 years (NOTE: The first three [3] patients on this study will be between the ages of 15-21 years).
  • TREATMENT: Barcelona Clinic liver cancer stage A, B or C (for patients with hepatocellular carcinoma only).
  • TREATMENT: Life expectancy of >= 12 weeks.
  • TREATMENT: Lansky or Karnofsky score >= 60%.
  • TREATMENT: Child-Pugh-Turcotte score < 7 (for patients with hepatocellular carcinoma only).
  • TREATMENT: Creatinine clearance as estimated by Cockcroft Gault or Schwartz >= 60 ml/min.
  • TREATMENT: Serum aspartate aminotransferase (AST) < 5 times upper limit of normal (ULN).
  • TREATMENT: Total bilirubin < 3 times ULN for age.
  • TREATMENT: International normalized ratio (INR) =< 1.7 (for patients with hepatocellular carcinoma only).
  • TREATMENT: Absolute neutrophil count > 500/ul.
  • TREATMENT: Platelet count > 25,000/ul (can be transfused).
  • TREATMENT: Hemoglobin (Hgb) >= 7.0 g/dl (can be transfused).
  • TREATMENT: Pulse oximetry > 90% on room air.
  • TREATMENT: Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study.
  • TREATMENT: Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
  • TREATMENT: Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

Exclusion Criteria

  • PROCUREMENT: 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).
  • PROCUREMENT: History of organ transplantation.
  • PROCUREMENT: Known human immunodeficiency virus (HIV) positivity.
  • PROCUREMENT: Active bacterial, fungal or viral infection (except hepatitis B or hepatitis C virus infections).
  • PROCUREMENT: Severe previous toxicity from cyclophosphamide or fludarabine.
  • TREATMENT: Pregnancy or lactation.
  • TREATMENT: Uncontrolled infection.
  • TREATMENT: Systemic steroid treatment (>= 0.5 mg prednisone equivalent/kg/day, dose adjustment or discontinuation of medication must occur at least 24 hours (hrs) prior to CAR T cell infusion).
  • TREATMENT: Known HIV positivity.
  • TREATMENT: Active bacterial, fungal or viral infection (except hepatitis B or hepatitis C virus infections).
  • TREATMENT: History of organ transplantation.
  • TREATMENT: 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).
  • TREATMENT: Severe previous toxicity from cyclophosphamide or fludarabine.

Locations & Contacts

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Andras Attila Heczey
Phone: 832-824-4233
Email: axheczey@txch.org
Texas Children's Hospital
Status: Active
Contact: Andras Attila Heczey
Phone: 832-824-4233
Email: axheczey@txch.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety of intravenous injection of escalating doses of anti-GPC3-CAR autologous T lymphocytes (GPC3-CAR T cells) in children with GPC3-positive solid tumors after lymphodepleting chemotherapy.

SECONDARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of GPC3-CAR T cells in treating patients with GPC3-positive solid tumors after lymphodepleting chemotherapy.

II. To assess the anti-tumor effect of the infused GPC3-specific CAR T cells in children with GPC3-positive solid tumors.

EXPLORATORY OBJECTIVES:

I. To assess the in vivo persistence, phenotype and functional activity of infused GPC3-CAR T cells in children with GPC3-positive solid tumors.

OUTLINE: This is a dose-escalation study of anti-GPC3-CAR autologous T lymphocytes.

Patients receive cyclophosphamide intravenously (IV) over 1 hour and fludarabine IV over 30 minutes on days -4 to -2. Patients then receive anti-GPC3-CAR autologous T lymphocytes IV over 5-10 minutes on day 0 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 2, 4, and 8 weeks, at 3, 6, 9, and 12 months, every 6 months for 4 years, and then annually for a total of 15 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Andras Attila Heczey

Trial IDs

Primary ID GAP H-39410
Secondary IDs NCI-2019-01955
Clinicaltrials.gov ID NCT02932956