Glypican 3-specific Chimeric Antigen Receptor Expressing T Cells for Hepatocellular Carcinoma (GLYCAR)

• Status: Recruiting
• Trial end date: 2036-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This study enrolls patients who have a type of cancer that arises from the liver called hepatocellular carcinoma. The cancer has come back, has not gone away after standard treatment, has spread outside of the liver or the patient cannot receive standard treatment. This research study uses special immune system cells called GLYCAR 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 into T cells that will make them recognize cancer cells and kill them. In preclinical studies, the investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33 that recognizes glypican-3, a protein found on almost all hepatocellular carcinoma cells (GPC3-CAR). This study will test T cells genetically engineered with a GPC3-CAR (GLYCAR T cells) in patients with hepatocellular carcinoma.

The GLYCAR 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 GLYCAR 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 GLYCAR T cells will help people with GPC3-positive hepatocellular carcinoma.

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

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Cancer Prevention Research Institute of Texas; Center for Cell and Gene Therapy, Baylor College of Medicine; 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

• Barcelona Clinic Liver Cancer Stage A, B or C

• GPC3-positive HCC

• Age >18 years

• Karnofsky score >60% (See appendix I)

• Life expectancy >12 weeks

• Child-Pugh-Turcotte score <8

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

Exclusion 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 hepatocellular carcinoma (HCC) which is unresectable, recurrent and/or metastatic

• Barcelona Clinic Liver Cancer Stage A, B or C

• GPC3-positive HCC

• Age ≥ 18 years

• Life expectancy of ≥ 12 weeks

• Karnofsky score ≥ 60%

• Child-Pugh-Turcotte score < 8

• Adequate organ function:

• creatinine 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 ≥7.0 g/dl (can be transfused)

• Pulse oximetry >90% on room air

• Recovered from acute toxic effects of all prior antineoplastic drugs before entering this study (including investigational drugs) based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).

• 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 T cell product

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

Exclusion Criteria:

• Eligible for complete tumor resection or liver transplantation.

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

• 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 III-IV and / or C-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