LMP2a-Specific Cytotoxic T-Lymphocytes Following CD45 Antibody for Lymphoma (ACDAL)
|First Received Date ICMJE||May 3, 2004|
|Last Updated Date||April 13, 2012|
|Start Date ICMJE||October 2003|
|Primary Completion Date||June 2011 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00082225 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||LMP2a-Specific Cytotoxic T-Lymphocytes Following CD45 Antibody for Lymphoma|
|Official Title ICMJE||Administration of LMP2a-Specific Cytotoxic T-Lymphocytes Following CD45 Antibody to Patients With Relapsed EBV-Positive Hodgkin's or Non-Hodgkin's Lymphoma|
Patients have a type of cancer called Hodgkin's lymphoma or non-Hodgkin's lymphoma, which has come back or not gone away or is at high risk for coming back after treatment, including the best treatment we know for this disease. We are asking the patient to volunteer to be in a research study using a new experimental therapy consisting of special immune system cells called LMP2 specific cytotoxic T lymphocytes in combination with a special protein called a monoclonal antibody.
Some patients with Hodgkin or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis of the lymphoma. EBV is found in the cancer cells of up to half the patients with lymphoma, suggesting that it may play a role in causing lymphoma. The cancer 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 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 that occurs after bone marrow and solid organ transplant 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 laboratory that recognized all 9 proteins and were able to prevent and treat post transplant lymphoma. However in Hodgkin disease and non-Hodgkin Lymphoma the tumor cells only express 2 EBV proteins. In a previous study we made T cells that recognized all 9 proteins and gave them to patients with Hodgkin disease. Some patients had a partial response to this therapy but no patients had a complete response. We think one reason may be that many of the T cells reacted with proteins that were not on the tumor cells. We are now trying to find out if we can improve this treatment by growing T cells that only recognize one of the proteins expressed on Lymphoma cells called LMP-2. These special T cells are called LMP-2 specific cytotoxic T-lymphocytes (CTLs).
In this study we also are trying to see if we can improve these results by treating patients first with a special protein called an antibody and then giving the EBV specific T cells. The reason for doing this is that EBV specific T cells have worked very well in bone marrow transplant patients to prevent and treat EBV cancers. These patients have very few of their own immune cells when we give them the trained T cells and therefore there is a lot of space for the trained cells to grow. We hope that we can improve the effect of the trained T cells in Hodgkin disease and non-Hodgkin Lymphoma patients by first temporarily removing your own T cells before giving the trained cells.
We first tested a biopsy of the tumor that has already been done to see if the tumor cells are EBV positive. We then got permission to take up to 60ml (12 teaspoonfuls) of blood from the patient or their donor on one or two occasions. We used this blood to grow T cells in the laboratory. We first grew a special type of cell called dendritic cells stimulate the T cells and we put a specially produced human virus (adenovirus) that carries the LMP-2a gene into the dendritic cells. These dendritic cells were then treated with radiation so they could not grow. They were then used to stimulate T cells. This stimulation trained the T cells to kill cells with LMP-2a on their surface. We then grew these LMP-2a specific CTLs by more stimulation with EBV infected cells (which we made from the patients blood or their donor's blood by infecting them with EBV in the laboratory). We also put the adenovirus that carries the LMP2 gene into these EBV infected cells so that we increase the amount of LMP2 that these cells have. Again, these EBV infected cells were treated with radiation so they could not grow. Once we made sufficient numbers of T cells we tested them to make sure they kill cells with LMP2a on their surface. These cells are now ready to give to the patient if they agree to being on this study.
We also took up to 500 ml (2 1/2 cups) of extra blood from the patient or their donor, which we froze. In case the patients own cells do not recover as we expect after the antibody and cell infusions, we can thaw these cells and give them back to the patient.
If the patient agrees to this treatment they will get treated with the CD45 antibodies for 4 days in a row and then 2-3 days later get a dose of LMP2 specific CTLs. If they are a female of child-bearing potential, we will give the patient a pregnancy test at least one week prior to the infusion. If they are pregnant, the patient will not be able to participate in the study. The study doctor will be notified.
The CD45 antibodies will be given to the patient through a vein for 6-8 hours and we will monitor the patient for at least 6 hours after the infusion. After the infusion we will check the levels of CD45 in the blood at 24 hours (optional) and/or at 48-72 hours after the last infusion to check the level is low enough to give the patient the CTLs.
The CTLs will be thawed and injected through a central line, if the patient has one, or through a vein in their arm over 10 minutes, after pretreatment with Tylenol and Benadryl. Because the cells are frozen in a preservative called DMSO which is breathed out through the lungs they will have a funny taste in their mouth for a few minutes after getting the cells in addition the DMSO may make the patients breath smell like garlic. We will then monitor them in clinic for 4 hours after the injection.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or the Methodist Hospital. We will follow the patient in the clinic after the CTL injection. If there is a reduction in the size of the lymphoma on CT or MRI scans as assessed by a radiologist, they can receive up to six additional doses of the T cells if they wish.
To learn more about the way the T cells are working and how long they last in the body, an extra 10-60 mls (2-12 teaspoonfuls) of blood will be taken on the days of the CD 45 antibody infusions, before and at the end of the CTL injection, as well as 3-4 days (taking blood on this day is optional) 1, 2, 4, 6 and 8 weeks after the CTL injections and then at 3,6,9 and 12 months. We will use this blood to look at the immune response in the blood to the patients cancer. In addition to the blood draws, because the patient has received cells that have been stimulated with cells that have a new gene the patient will need to be followed yearly for the next ten years so we can see if there are any long term side effects of the gene transfer. In the event of death, we will request permission to perform an autopsy to learn more about the effects of the treatment on the disease.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Study Arm (s)||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Estimated Completion Date||April 2012|
|Primary Completion Date||June 2011 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Note: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator's discretion after approval by the CCGT Protocol Review Committee and the FDA reviewer.
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00082225|
|Other Study ID Numbers ICMJE||14424-ACDAL, ACDAL|
|Has Data Monitoring Committee||Yes|
|Responsible Party||catherine bollard, Baylor College of Medicine|
|Study Sponsor ICMJE||Baylor College of Medicine|
|Information Provided By||Baylor College of Medicine|
|Verification Date||April 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP