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)
|ClinicalTrials.gov Identifier: NCT04093648|
Recruitment Status : Withdrawn (The key elements of this study were incorporated into another study.)
First Posted : September 18, 2019
Last Update Posted : May 20, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma Hepatoblastoma||Genetic: TEGAR T cells Drug: Cytoxan Drug: Fludarabine||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||January 2020|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||January 2038|
Experimental: TEGAR T cells + Fludarabine and Cytoxan
GPC3-CAR (TEGAR T cells) along with lymphodepleting chemotherapy (Cytoxan and Fludarabine) will be administered to patients with hepatocellular carcinoma.
Genetic: TEGAR T cells
Five 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: 1x10^7/m2 DL2: 3x10^7/m2 DL3: 1x10^8/m2 DL4: 3x10^8/m2 DL5: 1x10^9/m2 If DLTs are observed on DL1, patients will be enrolled on DL0 at 3x10^6/m2 dose.
The first patient on each dose level has to be 28 days post-CAR T cell infusion before the second patient can be enrolled. The doses are calculated according to the actual number of GPC3-CAR transduced T cells.
Other Name: GPC3-CAR T cells
Cyclophosphamide will be given at a dose of 500 mg/m2/day for 3 days given intravenously
Other Name: Cyclophosphamide
Fludarabine will be given at a dose of 30 mg/m2/day for 3 days given intravenously
- Dose Limiting Toxicity (DLT) Rate [ Time Frame: Start of lymphodepleting chemotherapy to 4 weeks post T cell infusion ]
- 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.
- Response Rate according [ Time Frame: 8 weeks post T-cell infusion ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04093648
|Principal Investigator:||Andras Heczey, MD||Baylor College of Medicine|