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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]

Phase 2
18 Years
Open (Enrolling)

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Trial Information

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
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.

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

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. ECOG performance status
10. Adequate organ function defined as: bilirubin <2x upper limit of normal (ULN),
creatinine <1.5x ULN, and sGPT <2.5x 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

6. Patients who are pregnant or breast-feeding

7. Patients with clinically significant heart disease (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 CML

12. Known allergy to Montanide ISA-51 VG adjuvant

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Time Frame:

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.

Safety Issue:


Principal Investigator

Jorge E. Cortes, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2006

Completion Date:

December 2014

Related Keywords:

  • Leukemia
  • Chronic Myelogenous Leukemia
  • Leukemia
  • Peptide Vaccine
  • PR1 Peptide
  • Imatinib
  • Gleevec
  • GM-CSF
  • Sargramostim
  • Leukine
  • Peginterferon alfa-2b
  • Peg-Intron
  • LeukineTM
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive



UT MD . Anderson Cancer Center Houston, Texas  77030