Potential of Immunotherapy to Convert a Complete Cytogenetic Remission in Chronic Myelogenous Leukemia to a Molecular Complete Remission: Randomized Phase II Study of Proteinase 3 PR1 Peptide Mixed With Montanide ISA-51 VG Adjuvant and Administered With GM-CSF and Peginterferon Alfa-2b [PEG-INTRON(R), Schering Corporation]
Your disease responded well to treatment with imatinib mesylate. It is in complete
cytogenetic remission. This means that the Philadelphia chromosome (Ph), a change in
genetic material that is believed to lead to leukemia, is no longer detectable (by the
standard chromosome analysis) in your bone marrow and blood cells. A molecular remission,
which is what researchers want you to achieve, means a greater reduction or a complete
elimination of the Ph.
The small amounts of disease can be detected using a technique called polymerase chain
reaction (PCR). This is a very powerful test that can detect very small amounts of disease
that can still be present in the bone marrow and/or blood cells.
PR1 is an experimental vaccine made from a protein that is found in large amounts in
leukemia cells in CML.
Imatinib mesylate (which you are already receiving as standard therapy) is designed to bind
to certain proteins on the tumor cells, which may prevent the cells from growing.
Interferon is a drug that was used as standard therapy for patients with CML before imatinib
mesylate was available. It can help the immune system to function more effectively (causing
leukemia cells to show more PR1), which may make leukemia cells a better target to be
Before you can start treatment on this study, you will have "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, including measurement of your vital signs (blood pressure, heart
rate, temperature, and breathing rate). You will have your complete medical history
recorded. You will have blood drawn (about 2 tablespoons) for routine tests. Women who
are able to have children must have a negative blood (about 1 teaspoon) or urine pregnancy
test. You will also have blood drawn (about 1 tablespoon) to see if you have the necessary
protein (called HLA-A2) needed for the vaccine to recognize your cells. You will also have
additional blood drawn (about 1 tablespoon) to test (using the PCR test) the levels of
leukemia in your blood. You will have a bone marrow aspiration. 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. You will have a chromosome
test done on the number of chromosomes in your bone marrow (collected from your bone marrow
aspiration). You will not have an additional procedure performed on you for this test. For
this test, all of your chromosomes in 20 cells in your bone marrow will be counted to see if
there may be any unhealthy changes (such as the Ph) present as well as how many may be
If you are found to be eligible to take part in this study, you will receive PR1 through a
small needle just under your skin (subcutaneous injection). Imatinib mesylate will continue
to be given to you by mouth at the dose that you are taking now as part of your standard
therapy. PR1 will be mixed with a substance called Montanide ISA 51 VG, which is a regular
procedure that will help your immune system respond to PR1.
You will be randomly assigned (as in the toss of a coin) to one of 2 treatment groups.
Participants in one group will receive a subcutaneous injection of interferon with each PR1
vaccination. Participants in the other group will receive PR1 vaccination without
Regardless of what group you are assigned to, you will also receive, with each PR1
vaccination, a growth hormone called GM-CSF. The purpose of GM-CSF is to boost your immune
system (in response to the PR1 vaccine) to help kill your leukemia. It is given as a
subcutaneous injection in your arms or your thighs.
All participants will receive a total of 4 doses of the PR1 vaccine. The first 3
vaccinations are given every 3 weeks, and the last vaccination is given 18 weeks after the
start of therapy in this study. You will receive all of these vaccinations at M. D.
Every time you come in for an injection of PR1, you will have a physical exam, including
measurement of your vital signs. You will have blood drawn (about 2 tablespoons) for
routine tests, and you will have blood drawn (about 1 tablespoon) for the PCR test. After
you receive the last vaccination, you will continue having the PCR test every 3 months to
test the level of leukemia in your blood and to see if your disease is responding to the
vaccine. You will have a bone marrow aspiration at 1 month and 6 months after the last
vaccination. To measure the response of your immune system to PR1, blood will be drawn
(about 2 tablespoons each) before the first vaccination, at Weeks 6, 18, 22 and 6 months
You will be taken off this study if intolerable side effects occur or your disease
progresses (comes out of remission).
This is an investigational study. PR1 mixed with Montanide ISA-51 VG is authorized by the
FDA for use in research only. Interferon and GM-CSF are FDA-approved and commercially
available. Up to 40 patients will take part in this study. All will be enrolled at M. D.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Blood draws to test polymerase chain reaction (PCR) every 3 months to test the level of leukemia in the blood and to see if disease is responding to the vaccine.
Jorge E. Cortes, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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