Phase II Combination Immunotherapy After ASCT for Advanced Myeloma to Study MAGE-A3 Immunizations With Hiltonol® (Poly-ICLC) Plus Transfer of Vaccine-Primed Autologous T Cells Followed by Lenalidomide Maintenance
Autologous stem cell transplant (ASCT) can lead to a complete or partial disappearance of
the myeloma in about 2 out of 3 patients. However, an ASCT only sometimes leads to a cure of
the myeloma. In about half the patients the myeloma comes back after about 1-2 years. In
about 90% of patients it comes back by about 10 years after transplant.
One possible way to improve upon the results of ASCT for myeloma is to help the body's
defense or immune system recover faster after transplant. Another way is to teach the body's
immune system to fight against the myeloma cells.
In two earlier research studies which included more than 100 patients, certain types of
immune cells called "T cells" or "T lymphocytes" were taken out of a patient's body using a
procedure called "apheresis". These cells were then grown up in the lab. After the
transplant, these T cells were put back into the patients. The replaced T cells helped the
patients'immune systems to recover faster after the transplant. In addition, when the T
cells were given back to patients they also received a vaccination. The vaccination or
injection was for a certain type of pneumonia germ called "pneumococcus". We found that most
patients built up protection against this pneumonia-causing germ. In another study, we used
a possible myeloma cancer vaccine. However, we found that less than half the patients
responded to this vaccine.
In this new study, we want to test a different type of myeloma cancer vaccine. This
different cancer vaccine is based on a protein called MAGE-A3. The MAGE-A3 protein is found
in about 50% of cases of myeloma. This vaccine consists of small pieces of protein (called
"peptides") which come from the MAGE-A3 protein. In order to help the immune system respond
better we will add two new steps. First we will add an immune system stimulant called
"Hiltonol®" to each vaccination. Hiltonol® is a chemical substance that turns on several
parts of the immune system. It may make the immune system better able to respond to the
vaccine. It has been tested in several hundred patients and has been used with about a dozen
different types of cancer and germ vaccines. Second, starting about 100 days after the
transplant procedure, patients will get a medicine called Lenalidomide. Lenalidomide is
already approved by the Food and Drug Administration (FDA) for treatment of myeloma. In this
study, we want to know whether Lenalidomide could help to improve the body's ability to
respond to the vaccinations and help to treat the myeloma itself.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
T-Cell responses against the MAGE-3 vaccine
T-cell responses against the MAGE-A3 vaccine as measured by proliferation & intracellular cytokine assays, at D100 post-transplant is the primary immunological endpoint.
At day 100 post transplant
Aaron Rapoport, M.D.
University of Maryland Greenebaum Cancer Center
United States: Food and Drug Administration
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|