Anti-CD19 CAR-T Cells With Inducible Caspase 9 Safety Switch for B-cell Lymphoma
Status:
Recruiting
Trial end date:
2038-10-12
Target enrollment:
Participant gender:
Summary
This research study combines 2 different ways of fighting disease: antibodies and T cells.
Both antibodies and T cells have been used to treat patients with cancers, and both have
shown promise, but neither alone has been sufficient to cure most patients. This study
combines both T cells and antibodies to create a more effective treatment. The treatment
being researched is called autologous T lymphocyte chimeric antigen receptor cells targeted
against the CD19 antigen (ATLCAR.CD19) administration.
Prior studies have shown that a new gene can be put into T cells and will increase their
ability to recognize and kill cancer cells. The new gene that is put in the T cells in this
study makes a piece of an antibody called anti-CD19. This antibody sticks to leukemia cells
because they have a substance on the outside of the cells called CD19. For this study, the
anti-CD19 antibody has been changed so that instead of floating free in the blood part of it
is now joined to the T cells. When an antibody is joined to a T cell in this way it is called
a chimeric receptor. These CD19 chimeric (combination) receptor-activated T cells seem to
kill some of the tumor, but they do not last very long in the body and so their chances of
fighting the cancer are unknown.
Preliminary results have shown that subjects receiving this treatment have experienced
unwanted side effects including cytokine release syndrome and neurotoxocity. In this study,
to help reduce cytokine release syndrome and/or neurotoxicity symptoms, the ATLCAR.CD19 cells
have a safety switch that, when active, can cause the cells to become dormant. These modified
ATLCAR.CD19 cells with the safety switch are referred to as iC9-CAR19 cells. If the subject
experiences moderate to severe cytokine release syndrome and or neurotoxicity as a result of
being given iC9-CAR19 cells, the subject can be given a dose of a second study drug, AP1903,
if standard interventions fail to alleviate the symptoms of cytokine release syndrome and/or
neurotoxicity. AP1903 activates the iC9-CAR19 safety switch, reducing the number of the
iC9-CAR19 cells in the blood. The ultimate goal is to determine what dose of AP1903 can be
given that reduces the severity of the cytokine release syndrome and/or neurotoxicity, but
still allows the remaining iC9-CAR19 cells to effectively fight the lymphoma.
The primary purpose of this study is to determine whether receiving iC9-CAR19 cells is safe
and tolerable in patients with relapsed/refractory B-cell lymphoma.
Phase:
Phase 1
Details
Lead Sponsor:
UNC Lineberger Comprehensive Cancer Center
Collaborators:
Bellicum Pharmaceuticals The V Foundation V Foundation