Hepatocellular Carcinoma Clinical Trial
Official title:
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
Verified date | May 2020 |
Source | Baylor College of Medicine |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | January 2038 |
Est. primary completion date | February 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Year and older |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Baylor College of Medicine | The Methodist Hospital System |
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Dose Limiting Toxicity (DLT) Rate | DLT rate will be calculated as the number of patients experiencing a DLT divided by the total number of patients receiving treatment. The NCI Common Toxicity Criteria V5.X will be used in grading toxicity with the exception of CRS and neurological toxicities that are related to T-cell infusions. CRS and neurological toxicities will be graded according to Appendix VI in the protocol. |
Start of lymphodepleting chemotherapy to 4 weeks post T cell infusion | |
Secondary | Response Rate according | Response rate will be estimated as the percent of patients whose best response is either complete remission or partial remission using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee and by the Immune-related Response Criteria. | 8 weeks post T-cell infusion |
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