Ignite Creation Date:
2024-05-06 @ 9:08 AM
Last Modification Date:
2024-10-26 @ 12:10 PM
Study NCT ID:
NCT02905188
Status:
COMPLETED
Last Update Posted:
2023-02-06
First Post:
2016-09-14
Brief Title:
Glypican 3-specific Chimeric Antigen Receptor Expressing T Cells for Hepatocellular Carcinoma GLYCAR
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Glypican 3-specific Chimeric Antigen Receptor Expressing T Cells as Immunotherapy for Patients With Hepatocellular Carcinoma
Status:
COMPLETED
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GLYCAR
Brief 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
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
Detailed Description:
A maximum of 30 subjects will participate in the treatment part of this study
Up to 180ml of blood is collected from patients to grow the T cells The T cells are grown and a retrovirus a special virus that can carry the GPC3 CAR gene into the T cells is used to genetically engineer them After the CAR gene is put into the T cells the investigators make sure that they are able to kill hepatocellular carcinoma cells in the laboratory
LYMPHODEPLETION CHEMOTHERAPY
Several studies suggest that the infused T cells need room to be able to proliferate and accomplish their functions and that this may not happen if there are too many other T cells in circulation Because of that participants will receive treatment with cyclophosphamide Cytoxan and fludarabine for 3 days before receiving the T-cell infusion These drugs will decrease the numbers of the participants own T cells before the investigators infuse the GLYCAR T CELLS
WHAT THE INFUSION WILL BE LIKE
After making these cells they will be frozen If the patient agrees to participate in this study at the time the patient is scheduled to be treated the cells will then be thawed and injected into the patient over 5 to 10 minutes The participant will receive the GLYCAR T CELLS 48-72 hours after completing the chemotherapy The participant may be pretreated with Tylenol acetaminophen and Benadryl diphenhydramine Tylenol and Benadryl are given to prevent a possible allergic reaction to the T cell administration
This is a dose escalation study which means that the investigators do not know the highest dose of GLYCAR T cells that is safe To find out the investigators will give the cells to at least 3 participants at one dose level If that is safe they will raise the dose given to the next group of participants The dose each patient gets will depend on how many participants get the agent before that patient and how they react The investigator will tell each patient this information This will help the patient think about possible harms and benefits Since the treatment is experimental what is likely to happen at any dose is not known
All of the Treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital
Medical tests before treatment
Physical exam and History
Blood tests to measure blood cells kidney and liver function and blood clotting INR
If the patient is infected with the hepatitis B virus HBV we will do a test to measure the levels of the virus
Pregnancy test if the patient is a female who can get pregnant
Measurements of the patients tumor by scans within 4 weeks before chemotherapy and the tumor marker alfa-fetoprotein AFP if the patients tumor produces this protein
Tumor biopsy
Medical tests during and after treatment
Physical exams and History
Blood tests to measure blood cells kidney and liver function and blood clotting INR
If the patient is infected with the hepatitis B virus HBV we will do a test to measure the levels of the virus
Measurements of the tumor maker alfa-fetoprotein AFP if the patients tumor produces this protein
Measurements of the patients tumor by scans 8 weeks after the infusion - 1 week
Tumor biopsy optional
FOLLOW-UP STUDIES
The investigators will follow the participant during and after the injections To learn more about the way the T cells are working in the participants body up to 60 mL 12 teaspoons of blood will be taken from the participant before the chemotherapy before the T-cell infusion 3 to 4 hours after the infusion 3 to 4 days after the infusion this time point is optional at 1 week 2 weeks 4 weeks 6 weeks and 8 weeks after the injection every 3 months for 1 year every 6 months for 4 years and then every year for the next 10 years Total time participation for this study will be 15 years
During the time points listed above if the T cells are found in the participants blood at a certain amount an extra 5mL of blood may need to be collected for additional testing
The investigators will use this blood to look for the frequency and activity of the cells that they have given that is to learn more about the way the T cells are working and how long they last in the body They will also use this blood to see if there are any long-term side effects of putting the new gene chimeric antigen receptor CAR into the cells In addition to the blood draws because the participants have received cells that have had a new gene put in them they will need to have long term follow up for 15 years so the investigators can see if there are any long term side effects of the gene transfer
Once a year participants will be asked to have their blood drawn and answer questions about their general health and medical condition The investigators may ask participants to report any recent hospitalizations new medications or the development of conditions or illness that were not present when they enrolled in the study and may request that physical exams andor laboratory tests be performed if necessary
Prior to procurement we confirmed GPC3-expression in your tumor by obtaining part of a biopsy sample that was done for clinical purposes We will obtain an additional tumor biopsy at 2 weeks after treatment for research purposes These samples will be used to look for GPC3-CAR T cells in the tumor and to learn more about the effects of the treatment on your disease
In the event that a tumor biopsy is performed for clinical reasons the investigators will request permission to obtain excess sample to learn more about the effects of the treatment on the participants disease In the event of death the investigators will request permission to perform an autopsy to learn more about the effects of the treatment on the participants disease and if there were any side effects from the cells with the new gene
If participants develop a second abnormal cancer growth significant blood or nervous system disorder during the trial a biopsy sample of the tissue will be tested if a sample can be obtained
Up to 180ml of blood is collected from patients to grow the T cells The T cells are grown and a retrovirus a special virus that can carry the GPC3 CAR gene into the T cells is used to genetically engineer them After the CAR gene is put into the T cells the investigators make sure that they are able to kill hepatocellular carcinoma cells in the laboratory
LYMPHODEPLETION CHEMOTHERAPY
Several studies suggest that the infused T cells need room to be able to proliferate and accomplish their functions and that this may not happen if there are too many other T cells in circulation Because of that participants will receive treatment with cyclophosphamide Cytoxan and fludarabine for 3 days before receiving the T-cell infusion These drugs will decrease the numbers of the participants own T cells before the investigators infuse the GLYCAR T CELLS
WHAT THE INFUSION WILL BE LIKE
After making these cells they will be frozen If the patient agrees to participate in this study at the time the patient is scheduled to be treated the cells will then be thawed and injected into the patient over 5 to 10 minutes The participant will receive the GLYCAR T CELLS 48-72 hours after completing the chemotherapy The participant may be pretreated with Tylenol acetaminophen and Benadryl diphenhydramine Tylenol and Benadryl are given to prevent a possible allergic reaction to the T cell administration
This is a dose escalation study which means that the investigators do not know the highest dose of GLYCAR T cells that is safe To find out the investigators will give the cells to at least 3 participants at one dose level If that is safe they will raise the dose given to the next group of participants The dose each patient gets will depend on how many participants get the agent before that patient and how they react The investigator will tell each patient this information This will help the patient think about possible harms and benefits Since the treatment is experimental what is likely to happen at any dose is not known
All of the Treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital
Medical tests before treatment
Physical exam and History
Blood tests to measure blood cells kidney and liver function and blood clotting INR
If the patient is infected with the hepatitis B virus HBV we will do a test to measure the levels of the virus
Pregnancy test if the patient is a female who can get pregnant
Measurements of the patients tumor by scans within 4 weeks before chemotherapy and the tumor marker alfa-fetoprotein AFP if the patients tumor produces this protein
Tumor biopsy
Medical tests during and after treatment
Physical exams and History
Blood tests to measure blood cells kidney and liver function and blood clotting INR
If the patient is infected with the hepatitis B virus HBV we will do a test to measure the levels of the virus
Measurements of the tumor maker alfa-fetoprotein AFP if the patients tumor produces this protein
Measurements of the patients tumor by scans 8 weeks after the infusion - 1 week
Tumor biopsy optional
FOLLOW-UP STUDIES
The investigators will follow the participant during and after the injections To learn more about the way the T cells are working in the participants body up to 60 mL 12 teaspoons of blood will be taken from the participant before the chemotherapy before the T-cell infusion 3 to 4 hours after the infusion 3 to 4 days after the infusion this time point is optional at 1 week 2 weeks 4 weeks 6 weeks and 8 weeks after the injection every 3 months for 1 year every 6 months for 4 years and then every year for the next 10 years Total time participation for this study will be 15 years
During the time points listed above if the T cells are found in the participants blood at a certain amount an extra 5mL of blood may need to be collected for additional testing
The investigators will use this blood to look for the frequency and activity of the cells that they have given that is to learn more about the way the T cells are working and how long they last in the body They will also use this blood to see if there are any long-term side effects of putting the new gene chimeric antigen receptor CAR into the cells In addition to the blood draws because the participants have received cells that have had a new gene put in them they will need to have long term follow up for 15 years so the investigators can see if there are any long term side effects of the gene transfer
Once a year participants will be asked to have their blood drawn and answer questions about their general health and medical condition The investigators may ask participants to report any recent hospitalizations new medications or the development of conditions or illness that were not present when they enrolled in the study and may request that physical exams andor laboratory tests be performed if necessary
Prior to procurement we confirmed GPC3-expression in your tumor by obtaining part of a biopsy sample that was done for clinical purposes We will obtain an additional tumor biopsy at 2 weeks after treatment for research purposes These samples will be used to look for GPC3-CAR T cells in the tumor and to learn more about the effects of the treatment on your disease
In the event that a tumor biopsy is performed for clinical reasons the investigators will request permission to obtain excess sample to learn more about the effects of the treatment on the participants disease In the event of death the investigators will request permission to perform an autopsy to learn more about the effects of the treatment on the participants disease and if there were any side effects from the cells with the new gene
If participants develop a second abnormal cancer growth significant blood or nervous system disorder during the trial a biopsy sample of the tissue will be tested if a sample can be obtained
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None