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

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ClinicalTrials.gov Identifier: NCT00665002
Recruitment Status : Completed
First Posted : April 23, 2008
Results First Posted : July 24, 2014
Last Update Posted : February 27, 2015
Sponsor:
Collaborator:
Innovive Pharmaceuticals
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE April 18, 2008
First Posted Date  ICMJE April 23, 2008
Results First Submitted Date  ICMJE June 25, 2014
Results First Posted Date  ICMJE July 24, 2014
Last Update Posted Date February 27, 2015
Study Start Date  ICMJE June 2008
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2014)
Number of Participants With Adverse Events (AEs) [ Time Frame: 12 weeks to 6 months ]
Toxicities were tabulated according to the NCI Common Toxicity (version 3.0) by grade and category. If more than one patient developed ≥ grade 3 non-hematologic toxicity or grade 4 hematologic toxicity, the study accrual was to 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 would have the option of terminating this trial permanently, amending the study protocol, or resuming the patient accrual.
Original Primary Outcome Measures  ICMJE
 (submitted: April 22, 2008)
Primary endpoints are safety, toxicity and immunogenicity of the WT1 vaccine. [ Time Frame: Interim analysis will be performed after enrollment of the first five evaluable patients. ]
Change History Complete list of historical versions of study NCT00665002 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2014)
Participants Whose Samples Demonstrated Immunological Response After Vaccination [ Time Frame: 12 weeks ]
Immune Response: Immune reactivity was measured for all participants. Immune response was measured by T cell proliferative response and DTH against WT-1 peptides. In patients with adequate samples, T cell gamma interferon release as measured by ELISPOT and/or multiparameter intracellular staining by flow cytometry were performed as well. ELISPOT Assay: CD4+ immune response, CD4+ and CD8+ response. The samples of participants' blood obtained at baseline and week 12 were tested for CD4 T cell proliferation, CD4 and CD8 T cell interferon release. Tetramer Analysis of WT1-specific Immune responses: subtle WT1 T cell expansion, positive by ELISPOT and T cell expansion. Delayed-type Hypersensitivity (DTH): measurable DTH response without overlap with ELISPOT or tetramer responders). Overall: any form of immune response.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2008)
Secondary endpoint is the antitumor effect of the vaccine. [ Time Frame: Interim analysis will be performed after enrollment of the first five evaluable patients. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Myeloid Neoplasms
Official Title  ICMJE Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Myeloid Neoplasms
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Biological: WT-1
    Immune responses were to 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 had an immunologic response and had not had disease progression could continue with up to 6 more vaccinations administered approximately every month. In that case, patients were to be reevaluated with bone marrows/immunologic studies after the 9th and 12th vaccination. In addition, patients would 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 Name: Analog Peptide Vaccine
  • Drug: Montanide
    The WT-1 vaccine is given with another substance, called Montanide, which clumps the WT-1 vaccine and thereby improves the immune response.
  • Drug: Sargramostim (GM-CSF)
    GM-CSF was administered at a dose 70 mcg (140ul) as a subcutaneous injection at the site of vaccination on day -2 and day 0.
Study Arms  ICMJE Experimental: WT-1 Analog Peptide Vaccine
Participants received 6 bi-weekly vaccinations over 10 weeks. WT-1 vaccine was given with Montanide. Participants also received an injection of Sargramostim (GM-CSF) two days before each vaccination and again on the day of the WT-1 injection at the same spot.
Interventions:
  • Biological: WT-1
  • Drug: Montanide
  • Drug: Sargramostim (GM-CSF)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 15, 2013)
16
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2008)
10
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00665002
Other Study ID Numbers  ICMJE MCC-15025
INNO-305 WT-1 ( Other Identifier: Innovive )
105946 ( Other Identifier: USF IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE Innovive Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Jeffrey Lancet, M.D. H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP