Ignite Creation Date:
2024-05-06 @ 8:07 PM
Last Modification Date:
2024-10-26 @ 3:20 PM
Study NCT ID:
NCT06251544
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-16
First Post:
2024-02-01
Brief Title:
TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor CAR T Cells for the Treatment of Metastatic Breast Cancer
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
TRAILBLASER TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor T Cells for the Treatment of Metastatic Breast Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
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:
None
Brief Summary:
The purpose of this study is to find the biggest dose of HTR2 T cells that is safe to see how long these cells last in the body to learn the side effects and to see if these cells are able to fight and kill HER2 expressing breast cancer
Patients eligible for this study have metastatic breast cancer that has HER2 expression and has progressed on at least one line of therapy This is a gene transfer research study using special immune cells called T cells T cells are a type of white blood cell that helps the body recognize and fight cancer cells
The body has different ways of fighting diseases and no single way seems perfect for fighting cancer This research combines two different ways of fighting cancer antibodies and T cells Antibodies are proteins that protect the body from infectious disease and possibly cancer T cells or T lymphocytes are special blood cells that can kill other cells including tumor cells Both antibodies and T cells have shown promise treating cancer but have not been strong enough to cure most patients
Previous research has found that investigators can put genes into T cells that helps them recognize cancer cells and kill them Investigators now want to see if by putting a new gene in those T cells to help recognize breast cancer cells expressing HER2 can kill the cancer cells In clinical trials for various cancer types that express HER2 our center engineered a CAR that recognizes HER2 and put this CAR into patients own T cells and gave them back Investigators saw that the cells did grow and patients did tolerate and respond to the treatment
Investigators will add a gene to the HER2 recognizing CAR T cells that will improve the T cells function Investigators know that some immune cells in the body can lower T cells ability to kill cancer cells Investigators have identified an antibody that will inactivate those immune suppressive cells thereby allowing T cells to survive better to recognize and kill cancer cells This antibody targets the Trail-R2 receptor and is referred to as TR2
Also investigators know that T cells need the support of cytokines to perform their immune functions There is evidence showing that the addition of interleukin 15 IL15 enhances CAR T cells ability to kill cancer cells As a result investigators also added IL15 to the HER2 and TR2 targeting CAR T cells HTR2 T cells
The HTR2 T cells are an investigational product not approved by the Food and Drug Administration
Patients eligible for this study have metastatic breast cancer that has HER2 expression and has progressed on at least one line of therapy This is a gene transfer research study using special immune cells called T cells T cells are a type of white blood cell that helps the body recognize and fight cancer cells
The body has different ways of fighting diseases and no single way seems perfect for fighting cancer This research combines two different ways of fighting cancer antibodies and T cells Antibodies are proteins that protect the body from infectious disease and possibly cancer T cells or T lymphocytes are special blood cells that can kill other cells including tumor cells Both antibodies and T cells have shown promise treating cancer but have not been strong enough to cure most patients
Previous research has found that investigators can put genes into T cells that helps them recognize cancer cells and kill them Investigators now want to see if by putting a new gene in those T cells to help recognize breast cancer cells expressing HER2 can kill the cancer cells In clinical trials for various cancer types that express HER2 our center engineered a CAR that recognizes HER2 and put this CAR into patients own T cells and gave them back Investigators saw that the cells did grow and patients did tolerate and respond to the treatment
Investigators will add a gene to the HER2 recognizing CAR T cells that will improve the T cells function Investigators know that some immune cells in the body can lower T cells ability to kill cancer cells Investigators have identified an antibody that will inactivate those immune suppressive cells thereby allowing T cells to survive better to recognize and kill cancer cells This antibody targets the Trail-R2 receptor and is referred to as TR2
Also investigators know that T cells need the support of cytokines to perform their immune functions There is evidence showing that the addition of interleukin 15 IL15 enhances CAR T cells ability to kill cancer cells As a result investigators also added IL15 to the HER2 and TR2 targeting CAR T cells HTR2 T cells
The HTR2 T cells are an investigational product not approved by the Food and Drug Administration
Detailed Description:
To make the T cells the investigators will take the patients blood and stimulate it with growth factors to make T cells grow Investigators use a retrovirus to insert HER CAR TR2 antibody and IL 15 genes into the T cells
HTR2 cells are generated from the patients T cells and are frozen 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 Patients will only get one dose of HTR2 T cells during the infusion If the patient has a good response and tolerance we may be able to repeat infusion in the future The patent may be pretreated with Tylenol and Benadryl to prevent possible allergic reaction to the T cell administration
If investigators need to stop the HTR2 T cells due to bad side effects investigators have inserted a gene called iCasp9 into the T cells This allows investigators to eliminate the HTR2 T cells in the blood when the gene comes into contact with a medication called Rimiducid The drug Rimiducid is not yet FDA approved and is an experimental drug but it has been tested in humans without bad side-effects Investigators will only use this drug to kill the T cells if necessary due to side effects Since investigators do not know exactly what dose will effectively stop HTR2 T cells in individual patients investigators will start at a low dose with the ability to increase the dose two more times based on how patients are doing Blood work will be done to ensure that the HTR2 T cells have been successfully eliminated
The treatment will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital
MEDICAL TESTS BEFORE TREATMENT
Before being treated patients will receive a series of standard medical tests
Physical exam and history
Blood tests to measure blood cells and organ function
Measurements of the tumor by scans at baseline prior to treatment
Ultrasound of the heart to make sure the patient has good baseline cardiac function
Additionally patients will need a biopsy of their tumor tissue to both confirm HER2 expression and to be used for research purposes
MEDICAL TESTS DURING AND AFTER TREATMENT
Within four weeks after infusion patients will be monitored on a weekly basis for dose limiting side effects of the HTR2 T cells
Physical exam and history
Blood tests to measure blood cells and organ function
After the initial six weeks patients will be monitored at a minimum every 3 months for the 1st year and every 6 months between 1 to year 5 or as frequently as deemed necessary
Physical exam and history
Blood tests to measure blood cells and organ function
Measurements of patients tumor by scans to assess treatment response
To learn more about the way T cells work in the patients body investigators will obtain up to 50 ml of blood from patient before chemotherapy before the T-cell infusion 1 to 4 hours 1 2 3 4 weeks and 8 weeks after infusion every 3 months for a year followed by every 6 months for 4 years and then every year for the the next 10 years Total participation on this study will be 15 years During the time points listed above if the T cells are found in the blood at a certain amount an extra half a tablespoon of blood may be needed for additional testing
Investigators will obtain one tissue biopsy within 4 weeks after infusion and as clinically indicated thereafter If additional clinically indicated tumor biopsies are obtained investigators will ask for a portion of the sample for research
HTR2 cells are generated from the patients T cells and are frozen 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 Patients will only get one dose of HTR2 T cells during the infusion If the patient has a good response and tolerance we may be able to repeat infusion in the future The patent may be pretreated with Tylenol and Benadryl to prevent possible allergic reaction to the T cell administration
If investigators need to stop the HTR2 T cells due to bad side effects investigators have inserted a gene called iCasp9 into the T cells This allows investigators to eliminate the HTR2 T cells in the blood when the gene comes into contact with a medication called Rimiducid The drug Rimiducid is not yet FDA approved and is an experimental drug but it has been tested in humans without bad side-effects Investigators will only use this drug to kill the T cells if necessary due to side effects Since investigators do not know exactly what dose will effectively stop HTR2 T cells in individual patients investigators will start at a low dose with the ability to increase the dose two more times based on how patients are doing Blood work will be done to ensure that the HTR2 T cells have been successfully eliminated
The treatment will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital
MEDICAL TESTS BEFORE TREATMENT
Before being treated patients will receive a series of standard medical tests
Physical exam and history
Blood tests to measure blood cells and organ function
Measurements of the tumor by scans at baseline prior to treatment
Ultrasound of the heart to make sure the patient has good baseline cardiac function
Additionally patients will need a biopsy of their tumor tissue to both confirm HER2 expression and to be used for research purposes
MEDICAL TESTS DURING AND AFTER TREATMENT
Within four weeks after infusion patients will be monitored on a weekly basis for dose limiting side effects of the HTR2 T cells
Physical exam and history
Blood tests to measure blood cells and organ function
After the initial six weeks patients will be monitored at a minimum every 3 months for the 1st year and every 6 months between 1 to year 5 or as frequently as deemed necessary
Physical exam and history
Blood tests to measure blood cells and organ function
Measurements of patients tumor by scans to assess treatment response
To learn more about the way T cells work in the patients body investigators will obtain up to 50 ml of blood from patient before chemotherapy before the T-cell infusion 1 to 4 hours 1 2 3 4 weeks and 8 weeks after infusion every 3 months for a year followed by every 6 months for 4 years and then every year for the the next 10 years Total participation on this study will be 15 years During the time points listed above if the T cells are found in the blood at a certain amount an extra half a tablespoon of blood may be needed for additional testing
Investigators will obtain one tissue biopsy within 4 weeks after infusion and as clinically indicated thereafter If additional clinically indicated tumor biopsies are obtained investigators will ask for a portion of the sample for research
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