Peptide Vaccinations to Treat Patients With Low-Risk Myeloid Cancers
Efficacy of Peptide (WT1) and Peptide(PRI) Vaccination for Patients With Low Risk Myeloid Malignancies
2 other identifiers
interventional
10
1 country
1
Brief Summary
This study will test the safety and effectiveness of two vaccines on slowing disease progression, improving blood counts, reducing the need for transfusions of blood and platelets, or achieving remission in patients with myelodysplastic syndrome (MDS, also known as myelodysplasia), acute myeloid leukemia (AML) or chronic myeloid leukemia (CML). The vaccines consist of peptides (parts of proteins) found in MDS, AML and CML stem cells, combined with a substance called "MontanideTM". They are administered with granulocyte- macrophage colony- stimulating factor (GM-CSF). The Montanide and the GM-CSF help the immune system respond to the vaccines. People 18 years of age or older with MDS, AML or CML may be eligible for this study. Participants receive six injections of the vaccines, one dose every other week for a total of 10 weeks. The injections are given in the upper arm, upper leg, or abdomen. A separate injection of GM-CSF is given in the same area as the vaccine injections. Subjects are observed for 2 hours after the first vaccination and at least 30 minutes after each subsequent vaccination for allergic reactions. In addition to the vaccination, subjects undergo the following:
- History and physical exam, chest x-ray, blood tests and bone marrow aspirate and biopsy before starting the vaccinations.
- Safety monitoring during vaccine administration (every other week for 10 weeks) with blood tests and check of vital signs.
- Follow-up safety monitoring (weeks 12 and 16) with blood tests every visit, chest x-ray at week 12 and bone marrow biopsy visit 16.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jun 2007
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2007
CompletedFirst Submitted
Initial submission to the registry
June 19, 2007
CompletedFirst Posted
Study publicly available on registry
June 20, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2010
CompletedResults Posted
Study results publicly available
July 9, 2014
CompletedJuly 12, 2021
June 1, 2014
2.8 years
June 19, 2007
April 30, 2013
June 15, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Experienced Inducing or Boosting of a Cellular Immune Response
Number of participants diagnosed with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) who experienced an inducing or boosting of a cellular immune response following Wilm's Tumor 1 (WT1) and PR1 vaccine. A T-cell immune response was considered positive if the frequencies of interferon (IFN-γ+) cluster of differentiation (CD8+) T cells in peptide-stimulated peripheral bloody mono-nucleated cells (PBMCs) were 2-fold or more higher than the frequencies of interferon (IFN-γ+) CD8+ T cells in unstimulated PBMCs and if there was a minimum of 0.05% Interferon (IFNγ+) CD8+ T cells (after subtracting the frequencies of interferon (IFNγ+) CD8+ T cells in unstimulated PBMCs). A significant vaccine-induced CD8+ T-cell response was defined as the emergence of detectable PR1 or WT1-specific CD8+ T cells when the pre-study analysis found no response, or a 2-fold increase in frequencies when responses were present before vaccination.
16 weeks
Secondary Outcomes (1)
Number of Participants Who Experienced a Hematological Response
16 weeks
Study Arms (1)
PR1/WT1 Vaccine Response in Participants With Low-Risk Myeloid Cancers
EXPERIMENTALSubjects were given 6 subcutaneous injects of PR1:169-177 in "Montanide" adjuvant and 6 subcutaneous injections of WT1:126-134 in "Montanide" adjuvant at 2 weekly intervals. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.
Interventions
Subjects were given 6 doses of PR1:169-177 in "Montanide" adjuvant and 6 doses of WT1:126-134 in "Montanide" adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.
Subjects were given 6 doses of PR1:169-177 in montanide adjuvant and 6 doses of WT-1:126-134 in Montanide adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.
Subjects were given 6 doses of PR1:169-177 in montanide adjuvant and 6 doses of WT-1:126-134 in Montanide adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.
Subjects were given 6 doses of PR1:169-177 in montanide adjuvant and 6 doses of WT-1:126-134 in Montanide adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.
Eligibility Criteria
You may qualify if:
- Diagnosed with MDS (B subtypes Refractory anemia (RA), Refractory anemia with ring sideroblasts (RARS) -Low Risk) (MDS with 5q- must have failed lenalidomide or been ineligible to receive it)
- Diagnosed with AML and in complete remission within 5 years of treatment with less than 5% marrow blasts
- Diagnosed with CML in chronic phase
- Unsuitable for stem cell transplantation (SCT) (age over sixty or unavailability of a fully-matched donor)
- made an informed decision not to undergo the transplant procedure
- are between 6 months 3 years following allogeneic SCT and fulfill the following criteria:
- % donor engraftment,
- Less than 5% blasts in marrow
- normal marrow cellularity
- Human leukocyte antigen (HLA-A020 1) positive at one allele
- Ages 18-85 years old
- Off all lympho-ablative chemotherapeutic agents
You may not qualify if:
- Hypoplastic MDS
- Relapsed AML
- CML in accelerated phase or blast crisis
- Hypocellular bone marrow (less than 20%)
- 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 or immunosuppressants within 14 days prior to study entry
- Co-morbidity of such severity that it would preclude the patient's ability to tolerate protocol therapy
- Predicted survival less than 28 days
- Pregnant or breast feeding (All female patients must have a urine pregnancy test within 1 week prior to vaccine administration)
- Unwilling to practice abstinence or effective contraception (men and women) during the study period.
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (1)
Rezvani K, Yong AS, Mielke S, Jafarpour B, Savani BN, Le RQ, Eniafe R, Musse L, Boss C, Kurlander R, Barrett AJ. Repeated PR1 and WT1 peptide vaccination in Montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8+ T cells in myeloid malignancies. Haematologica. 2011 Mar;96(3):432-40. doi: 10.3324/haematol.2010.031674. Epub 2010 Dec 6.
PMID: 21134985RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Minoo Battiwalla, MD
- Organization
- Hematology Branch, NHLBI
Study Officials
- PRINCIPAL INVESTIGATOR
Minocher Battiwalla, MD
National Institutes of Health- NHLBI
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 19, 2007
First Posted
June 20, 2007
Study Start
June 1, 2007
Primary Completion
April 1, 2010
Study Completion
April 1, 2010
Last Updated
July 12, 2021
Results First Posted
July 9, 2014
Record last verified: 2014-06