Ignite Creation Date:
2024-05-05 @ 5:00 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00368082
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-11-29
First Post:
2006-08-22
Brief Title:
AutologousAllogeneic TGFbeta-resistant LMP-specific CTL Lymphoma TGF-beta
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Administration of TGF-b Resistant LMP-Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
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:
TGF-beta
Brief Summary:
Patients have a type of lymph gland cancer called HD NHL or lymphoepithelioma these 3 diseases will be referred to as Lymphoma The lymphoma has come back or has not gone away after treatment This is a research study using special immune system cells called TGFb-resistant LMP-specific cytotoxic T lymphocytes DNR-CTL a new experimental therapy
Some patients with Lymphoma show signs of infection with the Epstein Barr virus EBV before or at the time of their Lymphoma diagnosis EBV is found in the cancer cells of up to 12 the patients with Lymphoma suggesting it may play a role in causing Lymphoma The cancer cells infected by EBV are able to hide from the bodys immune system and escape being killed by releasing a substance called Transforming Growth Factor-beta TGFb The investigators want to see if special white blood cells called T cells that have been given a gene that they hope will let them survive against TGFb and that have been trained to kill EBV infected cells can also survive in the blood and kill the tumor
Investigators have used this sort of therapy with specially trained T cells to treat a different type of cancer that occurs after bone marrow and solid organ transplant called post transplant lymphoma In this type of cancer they were able to successfully prevent and treat post transplant lymphoma However when they used a similar approach in HD some patients had a partial response to this therapy but no patients had a complete response In a follow-up study they tried to find out if they could improve this treatment by growing T cells that recognize 2 of the proteins expressed on Lymphoma cells called LMP-1 and LMP2a These special T cells were called LMP-specific cytotoxic T-lymphocytes CTLs Although some patients had tumor responses CTL therapy alone did not cure those who had a lot of disease Investigators think that a reason for this is that the tumor cells are releasing TGFb For this reason they want to find out if they can make the CTL resistant to TGFb by putting in a new gene called TGFb resistance gene Investigators hope that this will improve this treatment for relapsed lymphoma These TGFb-resistant LMP-specific CTLs are an investigational product not approved by FDA
The purpose of this study is to find the largest safe dose of TGFb resistant LMP-specific CTLs to learn what the side effects are and to see whether this therapy might help patients with Lymphoma
Some patients with Lymphoma show signs of infection with the Epstein Barr virus EBV before or at the time of their Lymphoma diagnosis EBV is found in the cancer cells of up to 12 the patients with Lymphoma suggesting it may play a role in causing Lymphoma The cancer cells infected by EBV are able to hide from the bodys immune system and escape being killed by releasing a substance called Transforming Growth Factor-beta TGFb The investigators want to see if special white blood cells called T cells that have been given a gene that they hope will let them survive against TGFb and that have been trained to kill EBV infected cells can also survive in the blood and kill the tumor
Investigators have used this sort of therapy with specially trained T cells to treat a different type of cancer that occurs after bone marrow and solid organ transplant called post transplant lymphoma In this type of cancer they were able to successfully prevent and treat post transplant lymphoma However when they used a similar approach in HD some patients had a partial response to this therapy but no patients had a complete response In a follow-up study they tried to find out if they could improve this treatment by growing T cells that recognize 2 of the proteins expressed on Lymphoma cells called LMP-1 and LMP2a These special T cells were called LMP-specific cytotoxic T-lymphocytes CTLs Although some patients had tumor responses CTL therapy alone did not cure those who had a lot of disease Investigators think that a reason for this is that the tumor cells are releasing TGFb For this reason they want to find out if they can make the CTL resistant to TGFb by putting in a new gene called TGFb resistance gene Investigators hope that this will improve this treatment for relapsed lymphoma These TGFb-resistant LMP-specific CTLs are an investigational product not approved by FDA
The purpose of this study is to find the largest safe dose of TGFb resistant LMP-specific CTLs to learn what the side effects are and to see whether this therapy might help patients with Lymphoma
Detailed Description:
Investigators will test a biopsy of the tumor to see if the tumor cells are EBV positive and to see if the subject is eligible for this study Then they will take some blood from the donor which is used to grow T cells First they will grow a special type of cell called dendritic cells or monocytes which stimulates the T cells and add a specially produced human adenovirus that carries the LMP1 and LMP-2a genes into the dendritic cellsor monocytes Addition of a gene to the cells is known as gene transfer These dendritic cells or monocytes are then used to stimulate T cells The stimulation trains the T cells to kill cells with LMP on their surface Investigators will then make more LMP-specific CTLs by stimulating them with EBV infected cells which we will make from the subjects blood or the donors blood by infecting them with EBV in the laboratory They also will put the adenovirus that carries the LMP1 and LMP2 genes into these EBV infected cells so that they increase the amount of LMP1 and LMP2 which these cells have
These EBV infected cells are treated with radiation so they cannot grow Once sufficient numbers of T cells are made investigators test them to see if they kill cells with LMP on their surface To make sure that these cells wont attack the subjects tissues they test the cells against the skin cells or against T cells that they grow in the laboratory
To make these CTL resistant to the effects of the TGFb released by the tumor we put in a new gene called a mutant TGFb receptor Investigators used a mouse retrovirus that had been changed to stop it from causing infection to add the mutant TGFb receptor to the cells
WHAT THE INFUSION WILL BE LIKE
After the cells are made they will be frozen If the subject agrees to participate in this study at the time they are scheduled to be treated the cells will then be thawed and injected into the subject over 10 minutes
Initially two doses of T cells will be given two weeks apart If after the second infusion there is a reduction in the size of the subjects lymphoma or no increase on CT or MRI scans as assessed by a radiologist the subject can receive up to six additional doses if it would be to their benefit if they would like to receive more doses and if there is enough product remaining to give them additional doses
This is a dose escalation study as investigators dont know what the highest dose of T cells with the new gene is safe To find out they will give the cells to 2 participants at one dose level If that is safe they will raise the dose given to the next group of participants The dose the subject will get will depend on how many participants get the agent before and how they react The investigator will tell the subject this information
All of the Treatments will be given by the Center for Cell and Gene Therapy at Texas Childrens Hospital or Houston Methodist Hospital
FOLLOW-UP STUDIES We will follow the subject after the injections Total time participation for this study will be 15 years
These EBV infected cells are treated with radiation so they cannot grow Once sufficient numbers of T cells are made investigators test them to see if they kill cells with LMP on their surface To make sure that these cells wont attack the subjects tissues they test the cells against the skin cells or against T cells that they grow in the laboratory
To make these CTL resistant to the effects of the TGFb released by the tumor we put in a new gene called a mutant TGFb receptor Investigators used a mouse retrovirus that had been changed to stop it from causing infection to add the mutant TGFb receptor to the cells
WHAT THE INFUSION WILL BE LIKE
After the cells are made they will be frozen If the subject agrees to participate in this study at the time they are scheduled to be treated the cells will then be thawed and injected into the subject over 10 minutes
Initially two doses of T cells will be given two weeks apart If after the second infusion there is a reduction in the size of the subjects lymphoma or no increase on CT or MRI scans as assessed by a radiologist the subject can receive up to six additional doses if it would be to their benefit if they would like to receive more doses and if there is enough product remaining to give them additional doses
This is a dose escalation study as investigators dont know what the highest dose of T cells with the new gene is safe To find out they will give the cells to 2 participants at one dose level If that is safe they will raise the dose given to the next group of participants The dose the subject will get will depend on how many participants get the agent before and how they react The investigator will tell the subject this information
All of the Treatments will be given by the Center for Cell and Gene Therapy at Texas Childrens Hospital or Houston Methodist Hospital
FOLLOW-UP STUDIES We will follow the subject after the injections Total time participation for this study will be 15 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| TGF-beta | OTHER | Baylor College of Medicine | None |