A Pilot Phase II Trial of a Synthetic Tumor-Specific Breakpoint Peptide Vaccine in Patients With Chronic Myeloid Leukemia (CML) and Minimal Residual Disease
Patients who are eligible to take part in this study have already responded well to
treatment with imatinib mesylate. Your disease is in what is called a complete cytogenetic
remission (i.e., The Philadelphia chromosome is no longer detectable.). However, there is
still a small amount of disease that can be detected using the most sensitive techniques
available. CML-VAX B2 and CML-VAX B3 are experimental vaccines made from the proteins that
cause leukemia cells in CML to behave abnormally. Imatinib mesylate is the standard therapy
for CML and blocks the function of this protein.
Before you can start treatment on this study, you will have what are called "screening
tests." These tests will help the doctor decide if you are eligible to take part in this
study. You will have a complete physical exam and medical history. Blood (about 2
tablespoons) will be collected for routine tests. You will also have a bone marrow
aspiration and a chromosome analysis of the number of chromosomes in the bone marrow. To
collect a bone marrow aspiration, an area of the hip or chest bone is numbed with
anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
Women who are able to have children must have a negative blood or urine pregnancy test.
You will also have some additional blood work (about 1 tablespoon) to test the levels of
leukemia in your blood. If you agree to participate in this study, this test will be
repeated 2 more times, about 2 weeks apart, before you can start vaccination. This is done
to get a good measure of the amount of disease you may have.
There are 2 different vaccines that can be used in this study, CML-VAX B2 and CML-VAX B3.
If you are found to be eligible to take part in this study, you will only receive one of
them. Which one you receive depends on the type of protein your leukemia makes, as these
vaccines are specific to each of the 2 most common proteins that may be produced by CML
All participants in this study will receive 1 of the 2 vaccines as well as imatinib
mesylate. Imatinib mesylate will continue to be given to you at the dose that you are
taking now. The vaccines will be mixed with a substance called montanide. This is a
standard procedure with vaccines and is done to try to make it more likely that you will
have a good immune response to the vaccines in general.
When the appropriate vaccine is selected for your use, you will receive an injection of the
vaccine once every 2 weeks for the first 8 weeks, once 3 weeks later, and then once every
month for a total of 15 vaccines in 12 months. You will receive the vaccine at M. D.
Anderson. The vaccine will be injected in the arms or the thighs. Two days before each
vaccination and again the day of each vaccination, you will receive an injection of a growth
hormone called GM-CSF (Leukine). The purpose of this injection is to boost your immune
system, in response to the vaccine, to specifically kill your leukemia. This injection is
given through a small needle and injected under your skin in your arms or your thighs. You
can be taught how to do this for yourself, but you may choose to have it given to you by a
member of the study staff.
Every time that you come in for an injection of the vaccine, you will also have a physical
exam and have routine blood work done (about 2 tablespoons). Every 3 months while receiving
the vaccine you will also have blood drawn (about 1 tablespoon) to test the level of
leukemia and to see if you are responding to the vaccine.
You will be taken off study if intolerable side effects occur or your disease comes out of
remission. About 2 weeks after the last injection of vaccine, you will have blood drawn
(about 1 tablespoon) to test the level of leukemia and to see if you are responding.
This is an investigational study. CML-VAX B2 and CML-VAX B3 are not FDA approved. The
vaccine and montanide will be free. Because you are receiving imatinib mesylate as part of
your standard of care, you and/or your insurance company or third-party payer will be
responsible for the costs of it. If GM-CSF is not covered by your insurance or other
third-party payer, it will be provided free of charge. A maximum of 60 patients will take
part in this study. A maximum of 20 will be enrolled at M. D. Anderson.
Optional Procedures: If you agree, additional blood tests (about 3 tablespoons each) will
be done at about 30 days before the first vaccine, after 6 months and 9 months from the
start of vaccination, and (about 10 tablespoons each) on the day of the first vaccine and
after 3 months and 2 weeks after the last vaccine to measure the response of your immune
system to the vaccine.
If you agree, a skin test will be done where a small amount of the proteins will be injected
under your skin for another measure of response of your immune system. If a small nodule
develops in the area where you receive this injection, it may represent an immune response.
This will be measured by your doctor or your nurse.
You do not have to agree to take part in the optional procedures in order to receive
treatment on this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response: One Log Decrease in BCR-ABL
Molecular response defined as reduction by one log of the circulating peripheral blood for reverse transcription polymerase chain reaction (RT-PCR) transcripts of BCR-ABL (tumor-specific oncogenic fusion protein) after two consecutive measurements. RT-PCR performed at 3 month intervals. Response categorized as either 'No Decrease' or 'Decrease' if one log reduction in BCR-ABL detected.
Jorge E. Cortes, M.D.
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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