Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Myeloid Neoplasms

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Innovive Pharmaceuticals
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00665002
First received: April 18, 2008
Last updated: January 9, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Leukemia
Biological: WT-1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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%.


Enrollment: 16
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)
Arms Assigned Interventions
Experimental: WT-1 Analog Peptide Vaccine
Patients will receive 6 bi-weekly vaccinations over 10 weeks.
Biological: WT-1
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).
Other Names:
  • Analog Peptide Vaccine
  • Montanide
  • Sargramostim
  • GM-CSF

Detailed Description:

Design:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cytologic or histologic diagnosis of acute myelogenous leukemia or myelodysplastic syndrome confirmed at Moffitt Cancer Center.
  • Patients with acute myelogenous leukemia will have completed induction chemotherapy, achieved first complete remission (CR) 1 or 2, and will have completed any planned postremission therapy (at discretion of treating physician),with no plan for allogenic or autologous transplant.
  • Patients with myelodysplastic syndrome who according to the International Prognostic Scoring System (IPSS) are category Int-2 or greater, with disease that relapsed, progressed, or not responded to at least 1 prior course of approved therapy for MDS (i.e. hypomethylating agent or lenalidomide).
  • Patients with AML/MDS must have documented WT-1 + disease. For purposes of this study, this may be either the demonstration of WT-1 protein on a pretreatment bone marrow biopsy or detectable disease with RQ-PCR. For patients in whom a bone marrow aspirate is not available or possible (e.g. "dry tap"), a peripheral blood sample may be used for WT-1 screening. In such cases, 10 cc of peripheral blood will be collected in a heparinized tube.
  • At least 4 weeks must have elapsed between the patient's last chemotherapy or radiation treatment and the first vaccination.
  • Karnofsky performance status ≥ 70%
  • Hematologic parameters:

    • Absolute neutrophil count ≥ 1000/mcL (except for MDS, for which the parameter is ≥ 500/mcL)
    • Platelets > 50 K/mcL (except for MDS for which the parameter is > 25 K/mcL and not transfusion dependent)
  • Biochemical parameters:

    • Total bilirubin ≤ 2.0 mg/dl
    • Aspartic transaminase (AST) and Alanine transaminase (ALT) ≤ 2.5 x upper limits of normal
    • Creatinine ≤ 2.0 mg/dl

Exclusion Criteria:

  • Pregnant or lactating women
  • Patients with leptomeningeal disease
  • Patients with active infection requiring systemic antibiotics, antiviral, or antifungal treatments
  • Patients with serious unstable medical illness
  • Patients taking systemic corticosteroids
  • Patients with central nervous system (CNS) involvement with cancer/leukemia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00665002

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Innovive Pharmaceuticals
Investigators
Principal Investigator: Jeffrey Lancet, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00665002     History of Changes
Other Study ID Numbers: MCC-15025, INNO-305 WT-1, 105946
Study First Received: April 18, 2008
Last Updated: January 9, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Myeloid
Monocytic
Hematopoietic
Neoplasms
Acute Myelogenous Leukemia
AML
Myelodysplastic Syndrome
MDS

Additional relevant MeSH terms:
Neoplasms
Leukemia
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 20, 2014