UARK 2003-26, A Pilot Study of MAGE-A3 and NY-ESO-1 Immunotherapy in Combination With DTPACE Chemotherapy and Autologous Transplantation in Multiple Myeloma
This is an experimental treatment that will consist of receiving peptide vaccinations as a
shot just under the skin (subcutaneous). We have chosen to vaccinate with peptides derived
from cancer proteins found in myeloma and other cancers. The purpose is to generate
anti-myeloma T-cells which will kill myeloma cells and nothing else.
The peptides are fragments from two tumor proteins called MAGE-A3 and NY-ESO-1. In order to
be eligible for the study your myeloma cells must express either MAGE-A3 or NY-ESO-1, and
your myeloma must be severe enough to require chemotherapy and stem cell transplantation.
You must also have the appropriate HLA tissue type.
Patients who have MAGE-A3 positive myeloma and are HLA-A*0101 or -B*35 positive will receive
the MAGE-A3 peptide vaccine.
Patients who have NY-ESO-1 positive myeloma and are HLA-A*0201 will receive the NY-ESO-1
Three injections with 300µg per injection (in 1.5mls) of peptide will be given
subcutaneously together with the adjuvant GM-CSF at 500µg (same site in 0.5 mls) at two-week
Your myeloma cells, obtained from a routine bone marrow aspirate, will be tested in the
laboratory for the presence of MAGE-A3 and/or NY-ESO-1 proteins. HLA tissue type will be
determined by standard methods in our Clinical Laboratory. This allows allocation of the
correct vaccine to each individual patient.
Prior to starting a 6-day course of chemotherapy called DTPACE, white blood cells will be
collected by a procedure called leukapheresis (leukapheresis no.1). Your white blood cells
will be frozen for the duration of the chemotherapy in order to protect these white blood
cells from the harmful effects of chemotherapy. After the chemotherapy is given, stem cells
will be collected by leukapheresis (PBSC collection) and stored until the time of
transplantation. After a short period of rest, the white blood cells from leukapheresis
no.1 will be thawed and re-infused. This will ensure that you will have white blood cells
that are in the best possible condition to respond to the peptide vaccines. A set of three
vaccinations with the peptides at two-week intervals will follow. The hope is that the
vaccinations will have generated precious anti-myeloma white blood cells.
You will again undergo leukapheresis (leukapheresis no.2) to collect the anti-myeloma white
blood cells, which will be frozen in order to protect these precious cells from the
chemotherapy drugs that will be infused just before the single or double auto-transplant.
A single dose of Melphalan will precede each transplant. The stem cells that were collected
after DTPACE will be given for the transplants. For those receiving two transplants, a
regimen of thalidomide with dexamethasone will be given for approximately 10 weeks between
the two transplants. You will stop your thalidomide 28 days before the second transplant.
After completion of the transplants, the anti-myeloma white blood cells collected with
leukapheresis no. 2 will be thawed and re-infused. These anti-myeloma cells will be boosted
by three further peptide vaccinations at two-week intervals.
Finally, after you have completed these three vaccinations you will undergo another
leukapheresis (no. 3). The anti-myeloma white blood cells collected with leukapheresis no. 3
will be frozen and stored for possible future use.
Six final vaccines will be given at monthly intervals to further amplify the anti-myeloma
white blood cells.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The Number of Participants Experiencing a Response to the Peptide Vaccines.
The peptides are fragments from two proteins MAGE-A3 and NY-ESO-1. There will be a series of 12 peptide vaccinations given as a subcutaneous (beneath the skin) injection (vaccines) at 2 week intervals resulting in an immune response to myeloma. The tumor peptides used in the vaccines are unique to myeloma, and it is not expected that there will be an immune response to normal organs. Myeloma cells must express MAGE-A3 or NY-ESO-1, be severe enough to require chemotherapy and stem cell transplantation and have appropriate HLA tissue type.
2 week intervals
Frits van Rhee, M.D., Ph.D.
Myeloma Institute for Research & Therapy
United States: Food and Drug Administration
|University of Arkansas for Medical Sciences/MIRT||Little Rock, Arkansas 72205|