T Cells co- Expressing a Second Generation Glypican 3-specific Chimeric Antigen Receptor With Cytokines Interleukin-21 and 15 as Immunotherapy for Patients With Liver Cancer (TEGAR)

• Status: Withdrawn
• Trial end date: 2038-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is for patients that have a type of cancer that arises from the liver, either called hepatocellular carcinoma or hepatoblastoma. The cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study will use special immune system cells called TEGAR 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. The investigator found from preclinical research that they can put a new gene into T cells that will help them recognize cancer cells and kill them. In our preclinical studies, several genes were made called a chimeric antigen receptor (CAR), from an antibody called GC33 that recognizes glypican-3, a protein found on almost all hepatocellular carcinoma cells and hepatoblastoma cells (GPC3-CAR). In the laboratory the investigators have been doing research into GPC3-CAR cells. They have selected the GPC3-CAR with the strongest ability to recognize hepatocellular carcinoma or hepatoblastoma cells for this study. This is a safety study where the investigator will be testing the ability of GPC3-CAR cells to identify and kill tumor cells in patients. The investigators also tested the effects of adding the molecule interleukin-15 (IL-15) alone or with another molecule called interleukin-21. The investigators found that IL-15 alone or together with IL-21 can help GPC3-CAR T cells last longer which helps them to kill more tumor cells. In this study the investigator will be testing the ability of GPC3-CAR cells to identify and kill tumor cells in patients. This is a study looking at safety and the investigators will therefore be starting with GPC3-CAR T cells alone in a set of patients. The first set of patients will receive GPC3-CAR T cells that also express IL-15. In the second group, the investigators will evaluate GPC3-CAR T cells that express both IL-15 and IL-21. If the investigators are able to safely give GPC3- CAR T cells, they will increase the dose of the combination cells in other patients. The product or dose level of cells that the participant will receive is based on when they are enrolled on the study.

The GPC3-CAR 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 GPC3-CAR 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 GPC3-CAR T cells will help people with GPC3-positive hepatocellular carcinoma or hepatoblastoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Texas Children's Hospital; The Methodist Hospital Research Institute; The Methodist Hospital System
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine

Criteria

Procurement Eligibility

Inclusion Criteria:

• Histology-proven hepatocellular carcinoma (HCC) which is unresectable, recurrent and/or metastatic OR recurrent or resistant hepatoblastoma (HB)

• Barcelona Clinic Liver Cancer Stage A, B or C

• GPC3-positive HCC or HB

• Age ≥ 1 years

• Karnofsky score >60% (See appendix I)

• Life expectancy >12 weeks

• Child-Pugh-Turcotte score <7 (for patients with cirrhosis only)

• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria:

• Heart failure of Class II-IV and / or B-D per NYHA Criteria

• 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 liver transplantation

• Known HIV positivity

• Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)

• Severe previous toxicity from cyclophosphamide or fludarabine

Treatment Eligibility

Inclusion Criteria:

• Histology-proven HCC which is unresectable, recurrent and/or metastatic or relapsed / refractory HB

• Barcelona Clinic Liver Cancer Stage A, B or C

• GPC3-positive HCC or HB

• Age ≥ 1 years

• Life expectancy of ≥ 12 weeks

• Karnofsky score ≥ 60%

• Child-Pugh-Turcotte score < 8

• Adequate organ function:

• clearance (as estimated by Cockcroft Gault) ≥ 60 ml/min

• serum AST< 5 times ULN

• total bilirubin < 3 times ULN for age

• INR ≤1.7

• absolute neutrophil count > 500/microliter

• platelet count > 20,000/microliter (can be transfused)

• Hgb ≥9.0 g/dl (can be transfused)

• Pulse oximetry >90% on room air

• Recovered from acute toxic effects of all prior chemotherapy before entering this study

• Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.

• Available autologous transduced CAR T cells

• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria:

• Pregnancy or lactation (for women at child-bearing age, birth control is required)

• Receiving investigational drugs within 2 weeks prior to treatment

• Hepatic encephalopathy

• Uncontrolled infection

• Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)

• Known HIV positivity

• Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)

• History of liver transplantation

• Heart failure of Class II-IV and / or B-D per NYHA Criteria

• 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)

• Severe previous toxicity from cyclophosphamide or fludarabine