PR1 Vaccination in Myelodysplastic Syndrome (MDS)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00893997
• Collaborator: The Vaccine Company (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 32
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Primary aim:

1. To determine the immunologic response, using a PR1-HLA-A2 tetramer assay, to 4 subcutaneous (SQ) injections of TVC-PR1 vaccine formulated in Montanide ISA 51 VG followed by granulocyte macrophage colony-stimulating factor (GM-CSF) in low risk and intermediate-1 myelodysplastic syndrome (MDS) patients.

Secondary aims:

1. To determine if non-immunologic responders to 4 subcutaneous (SQ) injections of TVCPR1 vaccine formulated in Montanide ISA 51 VG followed by GM-CSF can be converted to immunologic responders by administering 4 additional doses of TVC-PR1 vaccine formulated in Montanide ISA 51 VG followed by GM-CSF.

2. To determine the clinical response to 4 or 8 subcutaneous (SQ) injections of TVC-PR1 vaccine formulated in Montanide ISA 51 VG followed by GM-CSF in patients low risk and intermediate-1 MDS.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelodysplastic Syndrome	Biological: PR-1 vaccine	Phase 2

Detailed Description

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 To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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 testing.

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 study.

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Proteinase 3 PR1 Peptide Vaccine in Myelodysplastic Syndrome (MDS)
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PR-1 vaccine 4 injections of 0.5 mg PR1 peptide vaccine every 3 weeks.	Biological: PR-1 vaccine; 0.5 mg injections under the skin once every 3 weeks for a total of 4 vaccinations.; Other Names: PR1 Peptide Vaccine

Outcome Measures

Primary Outcome Measures

1. Patient Immunologic Response [29 weeks]

   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.

2. Number of Patients With Clinical Response [At 29 weeks]

   Clinical response based on the International Working Group (IWG) Response Criteria in myelodysplastic syndromes (MDS): 'Complete Response' or Hematologic Improvement' and 'No Clinical Response'. Clinical responses as assessed by standard criteria with bone marrow biopsy, cytogenetic studies (standard chromosome banding) and molecular studies 3 weeks after the last vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 methods

14. Serum bilirubin < 2 mg/ml

15. Serum creatinine </= 1.5 mg/ml

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 permitted.

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 <50ng/ml

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 antibiotics

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

26. Symptomatic pulmonary disease or FEV1, FVC and Carbon Monoxide Diffusing Capacity (DLCO) </= 50% predicted

27. History of Wegener's Granulomatosis or vasculitis

28. History of HIV positivity or AIDS

29. Prior history of AML

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	U.T. M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• The Vaccine Company

Investigators

• Principal Investigator: Guillermo Garcia-Manero, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00893997
• Other Study ID Numbers: 2005-0913
• First Posted: May 6, 2009
• Last Update Posted: Jul 16, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: myelodysplastic syndrome; MDS; PR1 Peptide Vaccine
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Vaccines

Study Results

Participant Flow

Recruitment Details	Recruitment Period: 01/09/07 through 03/24/08. All participants recruited at UT MD Anderson Cancer Center.
Pre-assignment Detail	Twelve patients were registered, two patients did not receive drug and were not included in the study group therefore ten patients were evaluable.

Arm/Group Title	PR-1 Vaccine
Arm/Group Description	4 injections of 0.5 mg PR1 peptide vaccine every 3 weeks.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	PR-1 Vaccine
Arm/Group Description	4 injections of 0.5 mg PR1 peptide vaccine every 3 weeks.
Overall Participants	10
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Patient Immunologic Response
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.
Time Frame	29 weeks

Outcome Measure Data

Analysis Population Description

Analysis on patients treated; study terminated early.

Arm/Group Title	PR-1 Vaccine
Arm/Group Description	4 injections of 0.5 mg PR1 peptide vaccine every 3 weeks.
Measure Participants	10
Immunological Response	3 30%
No Immunological Response	7 70%

2. Primary Outcome

Title	Number of Patients With Clinical Response
Description	Clinical response based on the International Working Group (IWG) Response Criteria in myelodysplastic syndromes (MDS): 'Complete Response' or Hematologic Improvement' and 'No Clinical Response'. Clinical responses as assessed by standard criteria with bone marrow biopsy, cytogenetic studies (standard chromosome banding) and molecular studies 3 weeks after the last vaccination.
Time Frame	At 29 weeks

Outcome Measure Data

Analysis Population Description

Analysis on patients treated; study terminated early.

Arm/Group Title	PR-1 Vaccine
Arm/Group Description	4 injections of 0.5 mg PR1 peptide vaccine every 3 weeks.
Measure Participants	10
Complete Response	0 0%
Hematological Improvement	1 10%
No Clinical Response	9 90%

Adverse Events

Time Frame	1 year and 11 months
Arm/Group Title	PR-1 Vaccine
Arm/Group Description	4 injections of 0.5 mg PR1 peptide vaccine every 3 weeks.
All Cause Mortality
	PR-1 Vaccine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PR-1 Vaccine
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
General disorders
Allergic Reaction	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	PR-1 Vaccine
	Affected / at Risk (%)	# Events
Total	6/10 (60%)
Gastrointestinal disorders
Nausea	1/10 (10%)	1
Vomiting	1/10 (10%)	1
Mucositis	1/10 (10%)	1
General disorders
Injection site reaction	4/10 (40%)	5
Allergic reaction	1/10 (10%)	1
Fatigue	2/10 (20%)	2
Bone pain	2/10 (20%)	2
Chill	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Puritis	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.