Proteinase 3 PR1 Peptide Mixed With Montanide ISA-51 VG Adjuvant and Administered With GM-CSF and PEG-INTRON(R)

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 killed.

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withdrawn through a large needle.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 present.

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 interferon.

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. Anderson.

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 after treatment.

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. Anderson.

Inclusion Criteria:

1. Patients >/= 18 years with Philadelphia chromosome (Ph)- or BCR/ABLpositive CML (as
determined by cytogenetics, FISH, or PCR).

2. Patients must have received imatinib therapy for at least 18 months and not have
increased their dose of imatinib in the last 6 months.

3. Patients must be in complete cytogenetic remission.

4. Patients must have detectable BCR-ABL transcript levels meeting at least one of the
following criteria: 1) Patient has never achieved a major molecular response (i.e.,
never reached levels <0.05%), and transcript levels have shown in at least two
consecutive measures separated by at least 1 month to have increased by any value, or

5. continued from above: 2) Achieved a major molecular response that has been lost with
an increase in transcript levels by at least 1-log over two consecutive analyses
separated by at least 1 month, or 3) BCR-ABL transcript levels have reached a plateau
defined as a ratio that is not more than 0.25-log (one fourth of a log) lower than the
lowest value obtained in the last at least 6 months, with at least 2 values obtained
during this period.

6. Patients must not have had a continuous interruption of imatinib therapy of greater
than 14 days or any interruptions totaling 6 weeks within the 6 months prior to
enrollment.

7. Patients must be HLA-A2 positive at one allele

8. Patients must give informed consent and sign an informed consent indicating that they
are aware of the investigational nature of this study in keeping with the policies of
the hospital.

9. Eastern Cooperative Oncology Group (ECOG) performance status
10. Adequate organ function defined as: bilirubin <2 times upper limit of normal (ULN),
creatinine <1.5 times ULN, and serum glutamate pyruvate transaminase (sGPT) <2.5 times
ULN.

11. Women of childbearing potential should practice effective methods of contraception.

Exclusion Criteria:

1. Patients with a history or clinical evidence of autoimmune disorders

2. Patients receiving immunosuppressive therapy including cyclosporine, or FK506 within 3
months of study entry

3. Chronic use (> 2 weeks) of greater than physiologic doses of corticosteroid agent
(dose equivalent to > 10 mg/day of prednisone) within 28 days of the first day of
study drug treatment (topical and inhaled corticosteroids are permitted)

4. GM-CSF or interferon administration within 1 month of first PR1 injection

5. Patients receiving any other investigational agents currently or within the past 4
weeks. Patients must have recovered from any adverse effects of investigational
therapy.

6. Patients who are pregnant or breast-feeding

7. Patients with clinically significant heart disease (New York Heart Association (NYHA)
Class III or IV)

8. Patients with positive cANCA

9. History of HIV positivity or AIDS

10. Chloroma at time of study screening

11. Prior vaccine therapy for Chronic myelogenous leukemia (CML)

12. Known allergy to Montanide ISA-51 VG adjuvant