Glypican 3-specific Chimeric Antigen Receptor Expressing T Cells for Hepatocellular Carcinoma (GLYCAR) (GLYCAR)
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|ClinicalTrials.gov Identifier: NCT02905188|
Recruitment Status : Not yet recruiting
First Posted : September 19, 2016
Last Update Posted : June 8, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma||Genetic: GLYCAR T cells Drug: Cytoxan Drug: Fludarabine||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Glypican 3-specific Chimeric Antigen Receptor Expressing T Cells as Immunotherapy for Patients With Hepatocellular Carcinoma|
|Estimated Study Start Date :||March 2019|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||October 2036|
Experimental: GLYCAR T cells + Fludarabine and Cytoxan
GPC3-CAR (GLYCAR T cells) along with lymphodepleting chemotherapy (Cytoxan and Fludarabine) will be administered to patients with hepatocellular carcinoma.
Genetic: GLYCAR 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:
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 14 days post 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
- Number of Patients with Dose Limiting Toxicity [ Time Frame: 6 weeks ]
DLT will be defined as any of the following that may, after consultation with the FDA, be considered possibly, probably, or definitely related to the study cellular products.
- Any Grade 5 event
- Non-hematologic dose-limiting toxicity is any Grade 3 or Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours
- Grade 2 to 4 allergic reaction to CAR T cell infusion.
- Hematologic dose limiting toxicity is defined as any Grade 4 hematologic toxicity that fails to return to Grade 2 or baseline (whichever is more severe) within 14 days.
- Grade 3 and 4 expected reactions due to CRS and neurotoxicity are seen with the use of CAR-based immunotherapy. Grade 3 cytokine release syndrome (CRS) infusion reactions and neurologic toxicity will only be reported to the FDA if they fail to return to Grade 1 within 7 days. Grade 4 CRS and neurologic toxicities will be reported to the FDA in an expedited fashion.
- Percent of Patients with best response as either complete remission or partial remission [ Time Frame: 6 weeks ]Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the two patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.
- Median T cell persistence [ Time Frame: 15 years ]as measured by PCR
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02905188
|Contact: Andras A Heczey, M.D.||firstname.lastname@example.org|
|United States, Texas|
|Houston Methodist Hospital||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Contact: Andras Heczey, MD email@example.com|
|Principal Investigator:||Andras A Heczey, M.D.||Baylor College of Medicine|