Ignite Creation Date:
2025-12-24 @ 3:31 PM
Ignite Modification Date:
2025-12-26 @ 10:18 PM
Study NCT ID:
NCT01555892
Status:
RECRUITING
Last Update Posted:
2025-12-10
First Post:
2012-03-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cytotoxic T-Lymphocytes for EBV-positive Lymphoma, GRALE
Sponsor:
Baylor College of Medicine
Organization:
Study Overview
Official Title:
Administration of Rapidly Generated EBV-Specific Cytotoxic T-Lymphocytes To Patients With EBV-Positive Lymphoma
Status:
RECRUITING
Status Verified Date:
2025-12
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:
GRALE
Brief Summary:
Subjects have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease or severe chronic active Epstein Barr Virus (CAEBV) which has come back, is at risk of coming back, or has not gone away after treatment, including the best treatment we know for these diseases.
Some of these patients show signs of virus that is called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono" or the "kissing disease") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. The cancer cells and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells, called GRALE T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor.
We have used this sort of therapy to treat a different type of cancer called post transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. We grew T cells in the lab that recognized all 9 proteins and were able to successfully prevent and treat post transplant lymphoma. However, in HD and NHL, T/NK-lymphoproliferative disease, and CAEBV, the tumor cells and B cells only express 4 EBV proteins. In a previous study, we made T cells that recognized all 9 proteins and gave them to patients with HD. Some patients had a partial response to this therapy but no patients had a complete response. We then did follow up studies where we made T cells that recognized the 2 EBV proteins seen in patients with lymphoma, T/NK-lymphoproliferative disease and CAEBV. We have treated over 50 people on those studies. About 60% of those patients who had disease at the time they got the cells had responses including some patients with complete responses. This study will expand on those results and we will try and make the T cells in the lab in a simpler faster way. These cells are called GRALE T cells. These GRALE T cells are an investigational product not approved by the FDA.
The purpose of this study is to find the largest safe dose of LMP-specific cytotoxic GRALE T cells created using this new manufacturing technique. We will learn what the side effects are and to see whether this therapy might help patients with HD or NHL or EBV associated T/NK-lymphoproliferative disease or CAEBV.
Some of these patients show signs of virus that is called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono" or the "kissing disease") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. The cancer cells and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells, called GRALE T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor.
We have used this sort of therapy to treat a different type of cancer called post transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. We grew T cells in the lab that recognized all 9 proteins and were able to successfully prevent and treat post transplant lymphoma. However, in HD and NHL, T/NK-lymphoproliferative disease, and CAEBV, the tumor cells and B cells only express 4 EBV proteins. In a previous study, we made T cells that recognized all 9 proteins and gave them to patients with HD. Some patients had a partial response to this therapy but no patients had a complete response. We then did follow up studies where we made T cells that recognized the 2 EBV proteins seen in patients with lymphoma, T/NK-lymphoproliferative disease and CAEBV. We have treated over 50 people on those studies. About 60% of those patients who had disease at the time they got the cells had responses including some patients with complete responses. This study will expand on those results and we will try and make the T cells in the lab in a simpler faster way. These cells are called GRALE T cells. These GRALE T cells are an investigational product not approved by the FDA.
The purpose of this study is to find the largest safe dose of LMP-specific cytotoxic GRALE T cells created using this new manufacturing technique. We will learn what the side effects are and to see whether this therapy might help patients with HD or NHL or EBV associated T/NK-lymphoproliferative disease or CAEBV.
Detailed Description:
Subjects (or their syngeneic donor) will give blood for investigators to make EBV-specific (GRALE) T cells in the lab. These cells will be grown and frozen for the subject.
In this study, patients may also receive cyclophosphamide and fludarabine. These two drugs are standard chemotherapy medicines and may be given before the T cells to make space in the blood for the T cells to grow after receiving them. These drugs will be given intravenously daily over three days.
The GRALE T cells will then be thawed and injected into the subject over 1-10 minutes. Initially, two doses of GRALE T cells will be given 2 weeks apart.
If after the 2nd infusion there is a demonstrated partial response or stable disease in the size of the lymphoma on CT or MRI scan as assessed by a radiologist, the subject can receive additional doses of the GRALE T cells if they wish (up to 6 times). Follow up testing will be collected just like after the 1st infusion.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
We will follow the subjects after the injections. They will either be seen in the clinic or the subject will be contacted by a research nurse yearly for 5 years.
If they receive additional doses of the GRALE T cells as described above, they will be followed until 5 years after the last dose of GRALE T-cells.
In this study, patients may also receive cyclophosphamide and fludarabine. These two drugs are standard chemotherapy medicines and may be given before the T cells to make space in the blood for the T cells to grow after receiving them. These drugs will be given intravenously daily over three days.
The GRALE T cells will then be thawed and injected into the subject over 1-10 minutes. Initially, two doses of GRALE T cells will be given 2 weeks apart.
If after the 2nd infusion there is a demonstrated partial response or stable disease in the size of the lymphoma on CT or MRI scan as assessed by a radiologist, the subject can receive additional doses of the GRALE T cells if they wish (up to 6 times). Follow up testing will be collected just like after the 1st infusion.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
We will follow the subjects after the injections. They will either be seen in the clinic or the subject will be contacted by a research nurse yearly for 5 years.
If they receive additional doses of the GRALE T cells as described above, they will be followed until 5 years after the last dose of GRALE T-cells.
Study Oversight
Has Oversight DMC:
True
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| GRALE | OTHER | BCM/CAGT | View | |
| P50CA126752 | NIH | None | https://reporter.nih.gov/quic… | View |