Ignite Creation Date:
2024-05-06 @ 9:15 AM
Last Modification Date:
2024-10-26 @ 12:11 PM
Study NCT ID:
NCT02932956
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-21
First Post:
2016-10-12
Brief Title:
Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Patients With Pediatric Solid Tumors GAP
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells as Immunotherapy for Patients With Pediatric Solid Tumors
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GAP
Brief Summary:
This study enrolls patients who have GPC3-positive solid tumors currently Patients may be considered if the cancer has come back has not gone away after standard treatment or the patient cannot receive standard treatment This research study uses special immune system cells called GAP 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 proteoglycan found on solid tumors including pediatric liver cancers GPC3-CAR This study will test T cells genetically engineered with a GPC3-CAR GAP T cells in patients with GPC3-positive solid tumors currently only enrolling liver tumors
The GAP 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 GAP 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 GAP T cells will help people with GPC3-positive solid tumors This study enrolls patients who have GPC3-positive solid tumors currently only enrolling liver tumors
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 proteoglycan found on solid tumors including pediatric liver cancers GPC3-CAR This study will test T cells genetically engineered with a GPC3-CAR GAP T cells in patients with GPC3-positive solid tumors currently only enrolling liver tumors
The GAP 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 GAP 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 GAP T cells will help people with GPC3-positive solid tumors This study enrolls patients who have GPC3-positive solid tumors currently only enrolling liver tumors
Detailed Description:
Approximately 18-30 subjects will participate in the treatment part of this study
Maximum of 180 mL of blood not exceeding 3mlkgday is collected from patients to grow the T cells and a retrovirus a special virus that can insert the GPC3 CAR gene into the T cells is used to genetically engineer them After the CAR gene was put into the T cells the investigators make sure that they are able to kill GPC3 positive solid tumor 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 GAP 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 be thawed and injected into the patient over 5 to 10 minutes The participant will receive the GAP T CELLS 48 to 72 hours after completing the chemotherapy
This is a dose escalation study which means that the investigators do not know the highest dose of GAP 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 the investigators will raise the dose given to the next group of participants The dose each patient gets depends 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 participant 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 Texas Childrens Hospital
Medical tests before treatment
Physical exam and History
Blood tests to measure blood cells kidney and liver function
Pregnancy test if the participant is a female who can get pregnant
If the participant is infected with the hepatitis B virus HBV the investigators will do a test to measure the levels of the virus
Measurements of the participants tumor by scans and the tumor marker alfa-fetoprotein AFP if the participants tumor produces this protein
Medical tests during and after treatment
Physical exams and History
Blood tests to measure blood cells kidney and liver function
If the participant is infected with the hepatitis B virus HBV the investigators will repeat the test and monitor the levels of the virus
Measurements of the participants tumor by scans 4-6 weeks after the infusion and AFP if applicable at 1 2 and 4 weeks after the infusion
Tumor biopsy between 2-4 weeks after the infusion and as clinically indicated thereafter For additional clinically indicated tumor biopsies investigators will ask for a portion of the sample for research
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 upto 12 teaspoons no more than 3mlkgday of blood will be taken from the participant before the chemotherapy before the T-cell infusion 1 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 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 participation time 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 5 mL 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 the investigators have given that is to learn more about the way the T cells are working and how long they last in the body The investigators 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 the participants 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 the participants will be asked to have their blood drawn and answer questions about their general health and medical condition The investigators may ask the participants to report any recent hospitalizations new medications or the development of conditions or illness that were not present when the participants enrolled in the study and may request that physical exams andor laboratory tests be performed if necessary
When 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
In addition the investigators would like to ask for participant permission to use tumor biopsy for research purposes only Associated risk with the biopsy will be discussed with each participant in detail in a procedure specific consent form The investigators will test the sample to see if the GAP T cells can be found in the tumor and what effect they had on the tumor cells
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
Maximum of 180 mL of blood not exceeding 3mlkgday is collected from patients to grow the T cells and a retrovirus a special virus that can insert the GPC3 CAR gene into the T cells is used to genetically engineer them After the CAR gene was put into the T cells the investigators make sure that they are able to kill GPC3 positive solid tumor 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 GAP 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 be thawed and injected into the patient over 5 to 10 minutes The participant will receive the GAP T CELLS 48 to 72 hours after completing the chemotherapy
This is a dose escalation study which means that the investigators do not know the highest dose of GAP 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 the investigators will raise the dose given to the next group of participants The dose each patient gets depends 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 participant 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 Texas Childrens Hospital
Medical tests before treatment
Physical exam and History
Blood tests to measure blood cells kidney and liver function
Pregnancy test if the participant is a female who can get pregnant
If the participant is infected with the hepatitis B virus HBV the investigators will do a test to measure the levels of the virus
Measurements of the participants tumor by scans and the tumor marker alfa-fetoprotein AFP if the participants tumor produces this protein
Medical tests during and after treatment
Physical exams and History
Blood tests to measure blood cells kidney and liver function
If the participant is infected with the hepatitis B virus HBV the investigators will repeat the test and monitor the levels of the virus
Measurements of the participants tumor by scans 4-6 weeks after the infusion and AFP if applicable at 1 2 and 4 weeks after the infusion
Tumor biopsy between 2-4 weeks after the infusion and as clinically indicated thereafter For additional clinically indicated tumor biopsies investigators will ask for a portion of the sample for research
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 upto 12 teaspoons no more than 3mlkgday of blood will be taken from the participant before the chemotherapy before the T-cell infusion 1 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 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 participation time 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 5 mL 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 the investigators have given that is to learn more about the way the T cells are working and how long they last in the body The investigators 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 the participants 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 the participants will be asked to have their blood drawn and answer questions about their general health and medical condition The investigators may ask the participants to report any recent hospitalizations new medications or the development of conditions or illness that were not present when the participants enrolled in the study and may request that physical exams andor laboratory tests be performed if necessary
When 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
In addition the investigators would like to ask for participant permission to use tumor biopsy for research purposes only Associated risk with the biopsy will be discussed with each participant in detail in a procedure specific consent form The investigators will test the sample to see if the GAP T cells can be found in the tumor and what effect they had on the tumor cells
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
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?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| GAP | OTHER | Baylor | None |