Administration of Autologous CAR-T CD19 Antigen With Inducible Safety Switch in Patients With Relapsed/Refractory ALL
Status:
Recruiting
Trial end date:
2036-10-01
Target enrollment:
Participant gender:
Summary
The body has different ways of fighting infection and disease. No single way is effective at
fighting cancer. This research study combines two different ways of fighting disease:
antibodies and T cells. Antibodies are proteins that protect the body from disease caused by
bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which
stops them from growing and causing bad effects. T cells, also called T lymphocytes, are
special infection-fighting blood cells that can kill other cells, including tumor cells or
cells that are infected. Both antibodies and T cells have been used to treat patients with
cancers. They both have shown promise, but neither alone has been sufficient to cure most
patients. This study combines both T cells and antibodies to try to create a more effective
treatment. This investigational treatment is called autologous T lymphocyte chimeric antigen
receptor cells targeted against the CD19 antigen (ATLCAR.CD19) administration.
In previous studies, it has been shown that a new gene can be put into T cells that will
increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes
make up the chemical structure carrying your genetic information that may determine human
characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells
makes a piece of an antibody called anti-CD19. This antibody can flow through the blood and
can find and stick to leukemia cells because these leukemia cells have a substance on their
surface called CD19. Anti-CD19 antibodies have been used to treat people with leukemia but
have not been strong enough to cure most patients. For this study, the anti-CD19 antibody has
been changed so that instead of floating free in the blood a piece of it is now joined to the
surface of the T cells. Only the part of the antibody that sticks to the leukemia cells is
attached to the T cells instead of the entire antibody. 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 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 of giving ATLCAR.CD19 cells to leukemia patients have been encouraging;
however, many subjects receiving this treatment have experienced unwanted side effects
including neurotoxicity and/or cytokine release syndrome (also referred to as cytokine storm
or an infusion reaction). Cytokines are small proteins that aract as e signals to other cells
and are the way cells talk to one another. During cytokine release syndromesyndrome, too many
cytokines are released and too many cells in your body react to their release. Symptoms
resulting from cytokine release syndrome vary from flu-like symptoms to more severe side
effects such as cardiac arrest, multi-system organ failure or death. We predict that about
50% of patients on this study will experience mild to severe cytokine release syndrome.
To help reduce cytokine release syndrome symptoms in future patients, a safety switch has
been added to the ATLCAR.CD19 cells that can cause the cells to become dormant or "go to
sleep". The safety switch is called inducible caspase 9 or iC9. The modified ATLCAR.CD19
cells with the safety switch are referred to as iC9-CAR19 cells.
The purpose of this study is to determine whether receiving the iC9-CAR19 cells is safe and
tolerable (there are not too many unwanted effects). If you experience severe cytokine
release syndrome or moderate to severe cytokine release syndrome that does not get better
once you are given standard treatments, you may be given a second study drug called
rimiducid. Similar studies showed that rimiducid can to turn on the safety switch, iC9 in
other therapies. Using rimiducid to activate the safety switch may be done in addition to
treating you according to hospital guidelines and making all efforts to immediately attend to
your cytokine release syndrome symptoms