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Phase 2 Study of Proteinase 3 PR1 Peptide Vaccine in Myelodysplastic Syndrome (MDS)

Phase 2
18 Years
Not Enrolling
Leukemia, Myelodysplastic Syndrome

Thank you

Trial Information

Phase 2 Study of Proteinase 3 PR1 Peptide Vaccine in Myelodysplastic Syndrome (MDS)

MDS cells over-produce proteins found in normal bone marrow cells. These proteins can be
used to stimulate the body's immune system to kill the MDS cells. PR-1 is a peptide derived
from a protein, and PR1 peptide vaccine is given to help immune cells kill MDS cells. The
vaccine is given together with granulocyte macrophage colony stimulating factor (GM-CSF),
which increases production of white blood cells and is intended to increase the number of
immune cells.

Before you can start treatment on the study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in the study. You will have a
bone marrow aspirate (about 1 tablespoon) for routine tests and for special studies. To
collect a bone marrow aspirate, an area of the hip is numbed with anesthetic and a small
amount of bone marrow is withdrawn through a large needle. Blood (about 6 tablespoons) will
be drawn. The blood tests are being done to compare pre-treatment blood counts to
post-treatment counts, and the aspirate is being done to allow comparison of the number of
MDS cells before and after treatment. Both the blood counts and aspirate will show whether
the therapy was successful. Women who are able to have children must have a negative blood
pregnancy test.

If you are found to be eligible to take part in this study, you will receive the PR-1
vaccine as an injection under the skin once every 3 weeks. You will receive a total of 4
vaccinations. Each vaccination requires 4 shots: 2 of PR-1 vaccine and 2 of GM-CSF. GM-CSF
is given to increase the number of immune cells that might respond to the vaccine and
eventually kill MDS cells. PR-1 vaccine is mixed with montanide ISA 51, which is used to
dissolve and stabilize the vaccine.

Blood (about 1 tablespoon) will be drawn for routine tests 1 time every 3 weeks and (about 3
tablespoons) will be drawn each time before you receive the vaccinations and at follow up
visits for the length of the study. You will have a bone marrow aspiration 4 weeks after the
4th and 8th vaccinations (about 1 tablespoon) for routine and for the special tests. These
tests will allow researchers to find out if the number of immune cells has increased,
whether these cells are able to attack the MDS cells, and whether the cells are related to a
change in blood counts. At this time (13 weeks from the first PR-1 vaccine), if your immune
system is reacting to the vaccinations, no further vaccinations will be given. This is to
avoid production of immune cells that might block the effects of the cells already produced
by the first 4 vaccinations. If, at this time (13 weeks from the first PR-1 vaccine), your
immune system is not reacting to the drug, you will be offered an additional 4 vaccinations.
These additional vaccinations will again be given once every 3 weeks. During this time,
blood (about 4 tablespoons) will again be drawn once every 3 weeks for routine and special

You will be taken off study at any time if the disease gets worse or intolerable side
effects occur.

Twenty-nine (29) weeks after beginning the study, blood (about 1 teaspoon) will be drawn to
check for a response to the vaccine. If you have not responded, you will be taken off

If you have responded, you will continue to be followed. Follow-up will involve monthly
routine blood tests (1 tablespoon of blood) for 6 months. These can be done at home with
results sent to M. D. Anderson. Every 3 months, you will return to M. D. Anderson for a
bone marrow aspirate and routine blood tests including the special testing studies.

This is an investigational study. This vaccine is authorized for use in research only and
is not commercially available. About 30 patients will take part in this multicenter study.
About 20 patients will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Must understand and voluntarily sign an informed consent form

2. Age >/= 18 years at the time of signing the informed consent form

3. Must be able to adhere to the study visit schedule and other protocol requirements

4. HLA-A2 positive at one allele

5. Diagnosis of myelodysplastic syndrome (MDS) and must meet all the following criteria

6. French-American-British (FAB) Class Refractory anemia (RA), Refractory Anemia with
Excess Blasts (RAEB), refractory anemia with ringed sideroblasts (RARS)

7. World Health Organization(WHO) Classification refractory anemia (RA), refractory
anemia with ringed sideroblasts(RARS), refractory cytopenia with multilineage
dysplasia (RCMD), refractory cytopenia with ringed sideroblasts (RCMD-RS) ,
refractory anemia with excess blasts type 1 (RAEB-1)

8. Less than 20% blasts on marrow aspirate

9. International Prognostic Scoring System (IPSS) risk groups Intermediate 1 or
transfusion dependent low risk.

10. Both de novo and therapy related MDS are eligible

11. Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1

12. Women of childbearing potential must have a negative serum pregnancy test within 30
days of starting study drug. A woman of child-bearing potential is a sexually mature
woman who has not undergone a hysterectomy or who has not been naturally
postmenopausal for at least 24 consecutive months (i.e., who has had menses at any
time in the preceding 24 consecutive months)

13. Male or female of child-bearing potential must agree to use adequate contraceptive

14. Serum bilirubin < 2 mg/ml

15. Serum creatinine
16. Serum ALT < 2 x upper normal limit

17. anti-neutrophil cytoplasmic antibody (cANCA) negative

18. Not received specific therapy for MDS for 4 weeks. However, supportive therapy is

Exclusion Criteria:

1. Marrow blasts on aspirate >/= 20%

2. Blood blasts > 1%

3. Inaspirable bone marrow

4. Myelosclerosis occupying >30% of marrow space

5. Iron absence on marrow examination or transferrin saturation <20% and serum ferritin

6. B-12 deficiency

7. Folate deficiency

8. History of immune related hematological disorder [i.e.,immune thrombopenia
purpura(ITP),autoimmune hemolytic anemia ( AIHA)]

9. Other causes of cytopenia not related to MDS (i.e., GI blood loss)

10. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form or that will place
the subject at unacceptable risk if he/she were to participate in the study or
confounds the ability to interpret the data

11. Prior allogeneic or syngeneic transplant

12. Prior solid organ transplant

13. Life expectancy severely limited by diseases other than MDS

14. Pregnant or lactating females

15. Prior vaccine therapy for MDS

16. Chronic use (>2 weeks) of greater than physiologic doses of a corticosteroid agent
(dose equivalent to >10 mg/day of prednisone) within 30 days of the first day of
study drug treatment. (Topical and inhaled corticosteroids are permitted)

17. Prior history of malignancy other than MDS (except basal cell or squamous cell
carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been
free of disease for >/= 5 years

18. Known allergy to incomplete Freund's adjuvant

19. Experimental therapy, cyclosporine, antithymocyte globulin, or FK506 within 3 months
of study entry

20. Treatment with androgenic hormones, danazol, colony stimulating factors,
erythropoietin, thalidomide, arsenic trioxide or other agents used to treat MDS
within four weeks of the first day of study treatment

21. refractory anemia with excess blasts in transformation (RAEB-t) (French-American
British (FAB) criteria ) or refractory anemia with excess blasts type2 (RAEB-2)
(World Health Organization (WHO) criteria)

22. Chloroma

23. Hypercalcemia

24. Progressive viral or bacterial infection. Patients are not eligible unless all
infections are resolved and the patient has remained afebrile for seven days without

25. Cardiac disease of symptomatic nature or cardiac ejection fraction < 40%

26. Symptomatic pulmonary disease or FEV1, FVC and Carbon Monoxide Diffusing Capacity
27. History of Wegener's Granulomatosis or vasculitis

28. History of HIV positivity or AIDS

29. Prior history of AML

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Patient Immunologic Response

Outcome Description:

Patients assessed after 4th vaccination for immunologic response categorized as 'Immunologic-Responders' or 'Non-Responders.' Immune response defined as an increase of ≥ 0.5 PR1-HLA-A2 tetramer cells/μl compared to the pre study absolute PR1-HLA-A2 tetramer cells/μl. Time period 29 weeks after study entry, with week 0 corresponding to 1st injection, and 8th injection thus being given at week 25, 29 weeks corresponds to 13 weeks after receipt of a 4th injection.

Outcome Time Frame:

29 weeks

Safety Issue:


Principal Investigator

Guillermo Garcia-Manero, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2006

Completion Date:

March 2009

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndrome
  • myelodysplastic syndrome
  • MDS
  • PR1 Peptide Vaccine
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia



U.T. M.D. Anderson Cancer Center Houston, Texas  77030