Myelodysplastic Syndrome (MDS)Phase 1NCT00270452
Safety of Peptide Vaccination for Patients With Myelodysplastic Syndrome
A Phase 1 study testing WT1 and PR1 Peptide Vaccine in people with Myelodysplastic Syndrome (MDS), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will test whether certain patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) can safely be vaccinated with two peptide vaccines derived from proteins called proteinase 3 (PR1) and Wilm's tumor-1 (WT1). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Myelodysplastic Syndrome (MDS)
- What is being tested?
- WT1 and PR1 Peptide Vaccine
- Type of treatment
- Vaccines
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Dec 2005to 26 Oct 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with FAB subtypes RA, RARS MDS (Low Risk)
- OR
- Diagnosed with AML and in complete remission within 5 years of treatment with less than 5 percent marrow blasts
- OR
- Diagnosed with CML In chronic phase
- OR
Show all 12Show fewer
- Diagnosed with MDS, AML or CML and are between 6 months-3 years following allogeneic SCT who fulfill the following criteria:
- 100 percent donor engraftment,
- less than 5 percent blasts in marrow
- normal marrow cellularity
- HLA-A0201 positive at one allele
- Ages 18 - 85 years old
Who cannot join
- Hypoplastic MDS
- Relapsed AML
- CML in accelerated phase or blast crisis
- Relapsed MDS, AML or CML following hematopoietic stem cell transplantation
- Hb less than 9 g/dl, neutrophil count less than 1 times 10(9)/1, and/ or platelet count less than 75 times 10(9)/1
- Hypocellular bone marrow
Show all 16Show fewer
- History of Wegener's granulomatosis
- Serologic antibody against proteinase-3 (ANCA positive)
- Previous allergic reaction to montanide adjuvant
- Positive test for HIV
- Treatment with systemic corticosteroids within 14 days prior to study entry
- Co-morbidity of such severity that it would preclude the subject's ability to tolerate protocol therapy
- Predicted survival less than 28 days
- Pregnant or breast feeding (All female subjects must have a urine pregnancy test within 1 week prior to vaccine administration)
- Enrolled in another drug or vaccine clinical trial during the study period
- Inability to comprehend the investigational nature of the study and provide informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Safety of WT1 and PR1 Peptide Vaccination for Patients With Myeloid Malignancies
This study will test whether certain patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) can safely be vaccinated with two peptide vaccines derived from proteins called proteinase 3 (PR1) and Wilm's tumor-1 (WT1). These proteins are produced in large amounts by cells of MDS, AML and CML patients. The peptides are combined with an "adjuvant" called Montanide to make the vaccines, and the vaccines are given with GM-CSF (sargramostim). Both Montanide and sargramostim help the immune system respond to the vaccines. The vaccines then activate the immune system to make specialized cells that search out and kill the MDS, AML and CML cells containing the two proteins.
Patients with MDS, AML or CML who are 18 years of age or older may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, chest x-ray, and bone marrow aspirate and biopsy. For the bone marrow biopsy, the area of the hip is anesthetized and a special needle is used to draw marrow from the hipbone.
Read more
Participants receive an injection (shot) of each peptide vaccine into deep tissue of the upper arm, upper leg, or the abdomen and two separate shots of sargramostim in the same area as the vaccine shots. Patients' vital signs (heart rate, breathing rate, temperature, blood pressure) are measured before and after they receive the vaccines and they are watched for 2 hours after the shots for possible side effects, such as chills, pain at the injection site, stomach upset, allergic reaction, low blood counts, and infection.
Patients return to the clinic 1, 2, 3 and 4 weeks after receiving the vaccines for a brief physical evaluation and blood tests. A chest x-ray is also done at the 4-week visit. Patients may receive whole blood or platelet transfusions if needed to treat the MDS, growth factors (filgrastim, erythropoietin, or others) if needed, and medications to treat any infections that may develop.
Read the detailed description
Myeloid malignancies including acute myeloid leukemia and the related disorders myelodysplastic syndrome (MDS) and myeloproliferative diseases represent a wide group of bone marrow stem cell malignancies. Some patients can be cured with chemotherapy or by allogeneic stem cell transplantation. However, a proportion of patients progress following chemotherapy and some relapse after transplantation. Therefore, there is need for studies of investigational agents to improve management of these patients.
The immunological graft-versus-leukemia (GVL) effect seen after allogeneic stem cell transplantation suggests that stimulating the patient's own T cell responses to MDS and leukemia with a vaccine might also retard disease progression and even achieve disease remissions. WT1 and PR1 were identified as target antigens because both antigens are highly expressed by CD34+ stem cells of most patients with myeloid malignancies but not by normal marrow cells. An immunotherapeutic approach to vaccinate against PR1 and WT1 antigens could induce T cell response against MDS and leukemic cells while sparing normal cells and by using a combination of two antigens the risk of disease escape by antigen down regulation should be further diminished.
Therefore, we propose to evaluate a vaccine composed of peptides derived from two proteins over-expressed in MDS and leukemia stem cells - proteinase 3 (PR1) and Wilms tumor-1 (WT1). This protocol, the first in a series of planned research, will evaluate the safety of a single dose of a combination of two peptide vaccines, namely PR1:169-177 and WT-1:126-134 in Montanide adjuvant administered concomitantly with GM-CSF (Sargramostim) in select subjects diagnosed with MDS, AML and CML.
- Conditions
- Myelodysplastic Syndrome (MDS)
- Being tested
- WT1 and PR1 Peptide Vaccine
- Keywords
- Myelodyplastic Syndrome (MDS), Wilm's tumor-1, Proteinase-3, Vaccine Therapy, Acute Myeloid Leukemia, Chronic Myeloid Leukemias, Myelodysplastic Syndrome, MDS
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WT1 and PR1 Peptide VaccineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety of and toxicity assoc. with a single dose of a comb. of PR1:169-177 and WT-1:126-134 peptide (in Montanide adjuvant) vaccination admin. concomitantly with GM-CSF (Sargramostim) in selected patients with myeloid malignancie...
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2005 (estimated)
- Study start22 Dec 2005
- Primary completion26 Oct 2007
- Study completion26 Oct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic Syndrome (MDS)Studies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Gregory J Kato, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00270452
- Sponsor's protocol ID
- 060062
- Other IDs
- 06-H-0062
- Status last verified
- 9 Feb 2012
- First submitted
- 24 Dec 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Estey EH. Prognosis and therapy of secondary myelodysplastic syndromes. Haematologica. 1998 Jun;83(6):543-9.
PubMed 9676028Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982 Jun;51(2):189-99.
PubMed 6952920Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002 Oct 1;100(7):2292-302. doi: 10.1182/blood-2002-04-1199.
PubMed 12239137Rezvani K, Yong AS, Mielke S, Savani BN, Musse L, Superata J, Jafarpour B, Boss C, Barrett AJ. Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood. 2008 Jan 1;111(1):236-42. doi: 10.1182/blood-2007-08-108241. Epub 2007 Sep 17.
PubMed 17875804
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of WT1 and PR1 Peptide Vaccination for Patients With Myeloid Malignancies
- ClinicalTrials.gov ID
- NCT00270452
- Acronym / sponsor ID
- 060062
- Conditions
- Myelodysplastic Syndrome (MDS)
- Keywords
- Myelodyplastic Syndrome (MDS), Wilm's tumor-1, Proteinase-3, Vaccine Therapy, Acute Myeloid Leukemia, Chronic Myeloid Leukemias, Myelodysplastic Syndrome, MDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 22 Dec 2005
- Primary completion
- 26 Oct 2007 (actual)
- Study completion
- 26 Oct 2007 (actual)
- First posted
- 26 Dec 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test whether certain patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) can safely be vaccinated with two peptide vaccines derived from proteins called proteinase 3 (PR1) and Wilm's tumor-1 (WT1). These proteins are produced in large amounts by cells of MDS, AML and CML patients. The peptides are combined with an "adjuvant" called Montanide to make the vaccines, and the vaccines are given with GM-CSF (sargramostim). Both Montanide and sargramostim help the immune system respond to the vaccines. The vaccines then activate the immune system to make specialized cells that search out and kill the MDS, AML and CML cells containing the two proteins.
Patients with MDS, AML or CML who are 18 years of age or older may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, chest x-ray, and bone marrow aspirate and biopsy. For the bone marrow biopsy, the area of the hip is anesthetized and a special needle is used to draw marrow from the hipbone.
Participants receive an injection (shot) of each peptide vaccine into deep tissue of the upper arm, upper leg, or the abdomen and two separate shots of sargramostim in the same area as the vaccine shots. Patients' vital signs (heart rate, breathing rate, temperature, blood pressure) are measured before and after they receive the vaccines and they are watched for 2 hours after the shots for possible side effects, such as chills, pain at the injection site, stomach upset, allergic reaction, low blood counts, and infection.
Patients return to the clinic 1, 2, 3 and 4 weeks after receiving the vaccines for a brief physical evaluation and blood tests. A chest x-ray is also done at the 4-week visit. Patients may receive whole blood or platelet transfusions if needed to treat the MDS, growth factors (filgrastim, erythropoietin, or others) if needed, and medications to treat any infections that may develop.
Detailed description
Myeloid malignancies including acute myeloid leukemia and the related disorders myelodysplastic syndrome (MDS) and myeloproliferative diseases represent a wide group of bone marrow stem cell malignancies. Some patients can be cured with chemotherapy or by allogeneic stem cell transplantation. However, a proportion of patients progress following chemotherapy and some relapse after transplantation. Therefore, there is need for studies of investigational agents to improve management of these patients.
The immunological graft-versus-leukemia (GVL) effect seen after allogeneic stem cell transplantation suggests that stimulating the patient's own T cell responses to MDS and leukemia with a vaccine might also retard disease progression and even achieve disease remissions. WT1 and PR1 were identified as target antigens because both antigens are highly expressed by CD34+ stem cells of most patients with myeloid malignancies but not by normal marrow cells. An immunotherapeutic approach to vaccinate against PR1 and WT1 antigens could induce T cell response against MDS and leukemic cells while sparing normal cells and by using a combination of two antigens the risk of disease escape by antigen down regulation should be further diminished.
Therefore, we propose to evaluate a vaccine composed of peptides derived from two proteins over-expressed in MDS and leukemia stem cells - proteinase 3 (PR1) and Wilms tumor-1 (WT1). This protocol, the first in a series of planned research, will evaluate the safety of a single dose of a combination of two peptide vaccines, namely PR1:169-177 and WT-1:126-134 in Montanide adjuvant administered concomitantly with GM-CSF (Sargramostim) in select subjects diagnosed with MDS, AML and CML.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Diagnosed with FAB subtypes RA, RARS MDS (Low Risk)
- OR
- Diagnosed with AML and in complete remission within 5 years of treatment with less than 5 percent marrow blasts
- OR
- Diagnosed with CML In chronic phase
Key exclusion criteria (16 listed)
- Hypoplastic MDS
- Relapsed AML
- CML in accelerated phase or blast crisis
- Relapsed MDS, AML or CML following hematopoietic stem cell transplantation
- Hb less than 9 g/dl, neutrophil count less than 1 times 10(9)/1, and/ or platelet count less than 75 times 10(9)/1
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 |
|---|---|---|
| WT1 and PR1 Peptide Vaccine | Drug | – |
Primary outcome
To evaluate the safety of and toxicity assoc. with a single dose of a comb. of PR1:169-177 and WT-1:126-134 peptide (in Montanide adjuvant) vaccination admin. concomitantly with GM-CSF (Sargramostim) in selected patients with myeloid malignancie...
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 9676028Estey EH. Prognosis and therapy of secondary myelodysplastic syndromes. Haematologica. 1998 Jun;83(6):543-9.
- Background: PubMed 6952920Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982 Jun;51(2):189-99.
- Background: PubMed 12239137Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002 Oct 1;100(7):2292-302. doi: 10.1182/blood-2002-04-1199.
- Derived from this study: PubMed 17875804Rezvani K, Yong AS, Mielke S, Savani BN, Musse L, Superata J, Jafarpour B, Boss C, Barrett AJ. Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood. 2008 Jan 1;111(1):236-42. doi: 10.1182/blood-2007-08-108241. Epub 2007 Sep 17.
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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.
Gregory J Kato, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing WT1 and PR1 Peptide Vaccine in people with Myelodysplastic Syndrome (MDS), run by National Heart, Lung, and Blood Institute (NHLBI) 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 12 inclusion and 16 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: finished, as of the sponsor's last update on 2 Jul 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To evaluate the safety of and toxicity assoc. with a single dose of a comb. of PR1:169-177 and WT-1:126-134 peptide (in Montanide adjuvant) vaccination admin. concomitantly with GM-CSF (Sargramostim) in selected patients with myeloid malignancie.... It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00270452, which also lists 4 linked publications.
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 2 Jul 2017.