Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Myeloid Neoplasms
The purpose of this study is to determine whether the WT-1 vaccine causes an immune response and is safe. The WT-1 vaccine is made up of protein pieces that the patient's immune system can recognize as abnormal.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Myeloid Neoplasms|
- Number of Participants With Adverse Events (AEs) [ Time Frame: 12 weeks to 6 months ] [ Designated as safety issue: Yes ]Toxicities will be tabulated according to the NCI Common Toxicity (version 3.0) by grade and category. If more than one patients develops ≥ grade 3 non-hematologic toxicity or grade 4 hematologic toxicity, the study accrual will be suspended immediately for a careful toxicity data evaluation. Depending upon the findings of such safety/toxicity data assessment and consultation with the supporting pharmaceutical company, the principal investigator of this trial will have the option of terminating this trial permanently, amending the study protocol, or resuming the patient accrual.
- Number of Participants With Immunological Response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]This vaccine will be considered promising if 6 or more out of 10 evaluable patients with AML/MDS have an immunological response at week 12 (after 6 vaccinations) i.e., with an immunological response of at least 50%.
|Study Start Date:||June 2008|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: WT-1 Analog Peptide Vaccine
Patients will receive 6 bi-weekly vaccinations over 10 weeks.
Immune responses will be evaluated at weeks 6 and 12 via delayed-type hypersensitivity, CD4 T cell proliferation, CD4 and CD8 T cell interferon release, as well as by bone marrow cytogenetics including polymerase chain reaction (PCR) to look for molecular evidence of disease. Patients who have an immunologic response and have not had disease progression may continue with up to 6 more vaccinations administered approximately every month. In that case, patients will be reevaluated with bone marrows/immunologic studies after the 9th and 12th vaccination. In addition, patients will undergo evaluations for residual disease including immunohistochemistry and/or quantitative polymerase chain reaction (RQ-PCR) for WT-1 expression (on selected patients), and multiparameter flow cytometry (AML/ MDS).
This will be a pilot trial evaluating the safety and immunogenicity of the WT-1 peptide vaccine in patients with hematologic malignancies. Ten patients with acute myelogenous leukemia (AML) or advanced myelodysplastic syndrome (MDS), will be enrolled. Patients will be vaccinated with a preparation of WT-1-derived native and synthetic peptides plus immunologic adjuvant Montanide ISA 51 VG (Seppic Pharmaceuticals, Fairfield, NJ) and Sargramostim (GM-CSF). One dose level will be tested.
Patients will receive 6 injections of the WT-1 vaccine. Doses will be given every 2 weeks. Each vaccine is given at a different location under the skin in the arm or leg. Patients will be monitored for 30 minutes after vaccination.
WT-1 vaccine is given with another substance, Montanide, which clumps the WT-1 vaccine and improves the immune response. Patients will also receive an injection of Sargramostim (GM-CSF) 2 days before each vaccination and again on the day of the WT-1 injection at the same spot. Sargramostim (GM-CSF) stimulates the body's white blood cells to boost the immune response. Patients may be taught to do the Sargramostim (GM-CSF) injection themselves in which case patients will be given a log sheet to record the injection time and location. If not, they will need to come for an additional 24 study visits.
To monitor their health while receiving the vaccine, patients will need the following tests and procedures as a part of regular cancer care.
- History and physical examination every 2 weeks
- Complete blood count (CBC) and comprehensive panel every 2 weeks
- Bone marrow aspirate at week 14 for patients with acute myelogenous leukemia or myelodysplastic syndrome.
Patients will need these tests and procedures to see whether the vaccine is causing an immune response:
- A skin test will be performed before patients start the study and again in the 8th and 14th weeks in which a small amount of the vaccine will be placed under the skin. Two days later, the site will be checked to see whether a bump or swelling has formed. Another substance which typically does cause a mild reaction (mumps) will also be placed under the skin to measure whether they have a normal immune reaction.
- We will take about 7 tablespoons of blood to measure their immune response. About 1 tablespoon of blood will be taken to measure the levels of WT-1 in their blood. Blood samples will be taken prior to receiving the first vaccination and prior to receiving the vaccination at weeks 6 and 12.
If the vaccine causes the patient to have an immune response, and their cancer does not grow, they may continue to receive the WT-1 vaccinations monthly for 6 more months. If this occurs, the patient will have a computed tomography (CT) scan or bone marrow test and immunology blood tests 2 weeks after the 9th and 12th vaccinations.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00665002
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Jeffrey Lancet, M.D.||H. Lee Moffitt Cancer Center and Research Institute|