A Randomized Phase I/II Trial Using a GM-CSF-Producing and CD40L-Expressing Bystander Cell Line (GM.CD40L) Vaccine in Combination With CCL21 for Patients With Stage IV Adenocarcinoma of the Lung
The vaccine will be made by mixing two kinds of cells: 1) some lung cancer cells, which have
been grown in the lab, and 2) experimental "bystander (present but not taking part in the
immune response)" cells. All the cells in the vaccine will be treated with high-dose X-rays
to make sure that none of them grow and cause more cancer. The bystander cells are human
cells that have been genetically changed to express GM-CSF and CD40L. These are called
"GM.CD40L". (That is the original cells, called K562, with the genes for human GM-CSF and
CD40L inserted into them). These changes are designed to help boost the participants immune
system to better fight the cancer in their body. GM-CSF is a hormone that is known to
stimulate bone marrow to make more white blood cells.
CCL21 is a chemokine (protein) that helps to recruit T cells (a type of white blood cell
that helps to protect the body from infections) and leads to hyper-responsive T cells. This
leads to heightened immune responses when T cells are exposed to both CCL21 and antigen (a
substance that when introduced into the body lead to production of an antibody)-presenting
cells (A cell that can "present" antigen in a form that T cells can recognize it ). The
induction of a strong cell-mediated immune response is the type of immunity expected to be
most involved in controlling cancer cell growth. A randomized trial of a vaccine consisting
of the GM.CD40L bystander cells and an equivalent number of allogeneic (taken from different
individuals) tumor cells plus or minus CCL21 is proposed.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With Progressive Free Survival (PFS)
Once the maximum tolerated dose (MTD) is established in the phase I, additional patients will be enrolled at this dose level to a total of 64 on a randomized phase II trial (32 per each arm). The primary endpoint for the trial will be 6-month progression free survival (PFS).
Jhanelle Gray, M.D.
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
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