Infusion of Genetically Modified T Cells: A Pilot Study of Tracking and Toxicity
This is a phase I study of to determine the safety of the administration of lymphocytes,
collected from the bone marrow donor. Donor lymphocytes are often administered in the case
of a relapsed cancer after allogeneic bone marrow transplantation, in the hope to reduce the
amount or size of the relapsed cancer. In this study, we will look for a decrease of the
size of the relapsed cancer.
By inserting genetic material (DNA) into the cells (lymphocytes) collected from the donor,
these cells will be genetically modified and made very sensitive to the killing effects of a
drug called ganciclovir, routinely used in the clinic after bone marrow transplantation to
treat virus infections in transplant patients.
This research study is to determine, if administration of the drug ganciclovir to the
recipient, after intravenous infusion of the genetically modified cells (lymphocytes) into
the recipient, will reduce or even eliminate a life threatening complication of allogeneic
transplantation, called graft versus host disease (GvHD). The drug ganciclovir will kill the
infused genetically modified donor cells (lymphocytes) so they cannot cause GvHD.
In summary, the overall purpose of this research study is to determine, if administration of
a seven day course of the drug ganciclovir to the donor lymphocyte recipient will either
decrease the severity of GvHD, or will decrease the number of cases with life-threatening
GvHD after donor lymphocyte infusions.
This study will also determine if insertion of a small piece of DNA (a small piece of
genetic material), makes these donor lymphocytes opened up and sensitive to the killing
effects of the drug ganciclovir, but at the same time does not harm the lymphocytes' ability
to reduce the amount or size of the cancer in the recipient. The DNA to be inserted into the
donor lymphocytes is transported into these cells by a type of virus called "retrovirus
vector". This retrovirus vector is made so the virus cannot divide (cannot make more of
itself), and cannot make cells or the recipient sick. Retroviruses do, however, allow for
the gene (DNA) they are carrying, to be permanently inserted into the genetic material of
the donor lymphocytes. Therefore, this inserted DNA will persist in the donor lymphocytes
for the life of the lymphocytes.
Finally, this study will also determine if the administration of genetically manipulated
donor lymphocytes is well tolerated.
The goal of this subproject is to see if an imaging procedure called 18FHBG-PET/CT can help
us see if the lymphocytes you received have gone to the sites in the body where the
anti-cancer effects are taking place.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies
John F. DiPersio, M.D., Ph.D.
Washington University School of Medicine
United States: Food and Drug Administration
09-0744 / 201103095
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