Most Closely HLA-Matched Allogeneic LMP1/2-Specific Cytotoxic T Lymphocytes for Treatment of Patients With Relapsed EBV-Associated Diseases
First, we will search our cell bank to see if there is a CTL line that is a match with the
subject and his/her donor. This matching is done using HLA type, which measures 6 proteins
on the cell surface. If HLA type has not been previously checked, we will do a blood draw
(half to one tablespoon) so that this can be done.
These CTL lines have been made at Baylor College of Medicine from donors for other
transplant patients or other normal donors from the National Marrow Donor Program. All
donors have been screened in the same way that we screen blood donors. When the CTL lines
were made, blood was taken from the donors and used to grow T cells. To do this, we first
grew a special type of cells called dendritic cells or monocytes and we put a specially
produced human virus (adenovirus) that carries the LMP genes into the dendritic cells or
monocytes. They were then used to stimulate T cells. This stimulation trained the T cells to
kill cells with LMP on their surface.
We then grew these LMP specific CTLs by more stimulation with EBV infected cells (made from
the same blood). We also put the adenovirus that carries the LMP genes into these EBV
infected cells so that we increased the amount of LMP that these cells had. 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 LMP on their surface
and froze them.
To make sure that these cells won't attack the subject's tissues, we will also test the
cells against his/her own cells, which we will grow in the laboratory.
If the level of circulating T-cells in the patient is relatively high, s/he will receive
one treatment of cyclophosphamide. This drug will decrease the numbers of the patient's own
T-cells before the investigators infuse the LMP-specific cytotoxic T-lymphocytes. If the
patient is already receiving chemotherapy, this may not be needed.
The LMP specific CTLs will be thawed and injected IV over 1-5 minutes. Initially, one dose
of T-cells will be given. If after the first dose, there is a reduction in the size of the
patient's disease, they can receive up to five additional doses of the T-cells if they wish.
This is a dose escalation study, which means that the doses of cells will be increased as
more patients are treated, as long as the lower doses are determined to be safe.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Patients with dose limiting toxicities after T-cell infusions
To determine the safety of intravenous injections of third-party, partially HLA- matched, allogeneic Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in patients with severe chronic active EBV (SCAEBV) infection or EBV-associated Hodgkin or non-Hodgkin lymphomas (HL/NHL), other lymphoproliferative disorders (LPD) or other malignancies (leiomyosarcoma and nasopharyngeal carcinoma)
Carlos A Ramos, MD
Baylor College of Medicine
United States: Food and Drug Administration
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