LeukemiaPhase 2NCT00893997
PR1 Vaccination in Myelodysplastic Syndrome (MDS)
A Phase 2 study testing PR-1 vaccine in people with Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndrome
- What is being tested?
- PR-1 vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Mar 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must understand and voluntarily sign an informed consent form
- Age >/= 18 years at the time of signing the informed consent form
- Must be able to adhere to the study visit schedule and other protocol requirements
- HLA-A2 positive at one allele
- Diagnosis of myelodysplastic syndrome (MDS) and must meet all the following criteria
- French-American-British (FAB) Class Refractory anemia (RA), Refractory Anemia with Excess Blasts (RAEB), refractory anemia with ringed sideroblasts (RARS)
Show all 18Show fewer
- 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)
- Less than 20% blasts on marrow aspirate
- International Prognostic Scoring System (IPSS) risk groups Intermediate 1 or transfusion dependent low risk.
- Both de novo and therapy related MDS are eligible
- Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1
- 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)
- Male or female of child-bearing potential must agree to use adequate contraceptive methods
- Serum bilirubin < 2 mg/ml
- Serum creatinine </= 1.5 mg/ml
- Serum ALT < 2 x upper normal limit
- anti-neutrophil cytoplasmic antibody (cANCA) negative
- Not received specific therapy for MDS for 4 weeks. However, supportive therapy is permitted.
Who cannot join
- Marrow blasts on aspirate >/= 20%
- Blood blasts > 1%
- Inaspirable bone marrow
- Myelosclerosis occupying >30% of marrow space
- Iron absence on marrow examination or transferrin saturation <20% and serum ferritin <50ng/ml
- B-12 deficiency
Show all 29Show fewer
- Folate deficiency
- History of immune related hematological disorder [i.e.,immune thrombopenia purpura(ITP),autoimmune hemolytic anemia ( AIHA)]
- Other causes of cytopenia not related to MDS (i.e., GI blood loss)
- 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
- Prior allogeneic or syngeneic transplant
- Prior solid organ transplant
- Life expectancy severely limited by diseases other than MDS
- Pregnant or lactating females
- Prior vaccine therapy for MDS
- 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)
- 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
- Known allergy to incomplete Freund's adjuvant
- Experimental therapy, cyclosporine, antithymocyte globulin, or FK506 within 3 months of study entry
- 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
- 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)
- Chloroma
- Hypercalcemia
- 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
- Cardiac disease of symptomatic nature or cardiac ejection fraction < 40%
- Symptomatic pulmonary disease or FEV1, FVC and Carbon Monoxide Diffusing Capacity (DLCO) </= 50% predicted
- History of Wegener's Granulomatosis or vasculitis
- History of HIV positivity or AIDS
- Prior history of AML
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T. M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase 2 Study of Proteinase 3 PR1 Peptide Vaccine in Myelodysplastic Syndrome (MDS)
Primary aim:
- 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.
Read more
Secondary aims:
- 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.
- 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.
Read the 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.
- Conditions
- Leukemia, Myelodysplastic Syndrome
- Being tested
- PR-1 vaccine
- Keywords
- myelodysplastic syndrome, MDS, PR1 Peptide Vaccine
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PR-1 vaccineBiological
Also called PR1 Peptide Vaccine
0.5 mg injections under the skin once every 3 weeks for a total of 4 vaccinations.
| Study group | Role | What they receive |
|---|---|---|
| PR-1 vaccine | Experimental | 4 injections of 0.5 mg PR1 peptide vaccine every 3 weeks. Receives: Biological: PR-1 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient Immunologic Response
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.
Measured: 29 weeks
Number of Patients With Clinical Response
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.
Measured: At 29 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2009 (estimated)
- Study startJul 2006
- Primary completionMar 2009
- Study completionMar 2009
Why it stopped: The trial was ended per sponsor due to slow accrual rates.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Vaccine Company
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00893997
- Sponsor's protocol ID
- 2005-0913
- Status last verified
- Jul 2012
- First submitted
- 4 May 2009
- Last updated
- 16 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Proteinase 3 PR1 Peptide Vaccine in Myelodysplastic Syndrome (MDS)
- ClinicalTrials.gov ID
- NCT00893997
- Acronym / sponsor ID
- 2005-0913
- Conditions
- Leukemia, Myelodysplastic Syndrome
- Keywords
- myelodysplastic syndrome, MDS, PR1 Peptide Vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was ended per sponsor due to slow accrual rates.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- The Vaccine Company
- Study start
- Jul 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 6 May 2009 (estimated)
- Results
- Posted 12 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary aim:
- 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:
- 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.
- 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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PR-1 vaccine | Experimental | Biological: PR-1 vaccine4 injections of 0.5 mg PR1 peptide vaccine every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Must understand and voluntarily sign an informed consent form
- Age >/= 18 years at the time of signing the informed consent form
- Must be able to adhere to the study visit schedule and other protocol requirements
- HLA-A2 positive at one allele
- Diagnosis of myelodysplastic syndrome (MDS) and must meet all the following criteria
Key exclusion criteria (29 listed)
- Marrow blasts on aspirate >/= 20%
- Blood blasts > 1%
- Inaspirable bone marrow
- Myelosclerosis occupying >30% of marrow space
- Iron absence on marrow examination or transferrin saturation <20% and serum ferritin <50ng/ml
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PR-1 vaccineAlso: PR1 Peptide Vaccine0.5 mg injections under the skin once every 3 weeks for a total of 4 vaccinations. | Biological | PR-1 vaccine |
Primary outcome
Patient Immunologic Response
Time frame: 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.
Number of Patients With Clinical Response
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
Related trials for Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guillermo Garcia-Manero, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PR-1 vaccine in people with Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient Immunologic Response (time frame: 29 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2012.