Clinical Trials

WT1 Therapeutic Leukemia DNA Vaccine

Following strong pre-clinical data, in 2011 the U.K.’s University of Southampton began enrolling patients in a phase II clinical trial (WIN Trial) to treat leukemia utilizing Inovio's ELGEN 1000 automated vaccine delivery device. This open-label, multi-center clinical trial being run by the University of Southampton is evaluating a DNA vaccine to treat chronic myeloid leukemia and acute myeloid leukemia. Financial support for the trial is being provided by the UK research charity Leukemia and Lymphoma Research (LLR) and by the Efficacy and Mechanisms Evaluation (EME) program (which is funded by the UK Medical Research Council and managed by the UK National Institute for Health Research). The DNA vaccine was developed at the University of Southampton with funding from LLR and the charity Cancer Research UK.

The single dose level, phase II study, called "WT1 immunity via DNA fusion gene vaccination in hematological malignancies by intramuscular injection followed by intramuscular electroporation" is designed to recruit two patient groups. One group is planned to recruit up to 37 CML patients and the other up to 37 AML patients. All participants will initially receive six doses of two DNA vaccines (called p.DOM-WT1-37 and p.DOM-WT1-126) delivered at four week intervals. Vaccine responders may continue with booster vaccinations every three months out to 24 months.

The primary endpoints will be molecular response to a disease marker called BCR-ABL in CML patients and time to disease progression in AML patients. The study will also monitor WT1 transcript levels, immune responses to the WT1 antigen, time to progression and overall survival, and two-year survival in the AML group. The trial will take place at hospitals in Southampton, London and Exeter over the next two years. Regulatory approval to start this clinical study was provided by the UK Medicines and Healthcare Products Regulatory Authority (MHRA) and Gene Technology Advisory Committee (GTAC).

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Study Data

WT1 Therapeutic Leukemia DNA Vaccine

Preclinical data from mice showed strong induction of antigen-specific CD8+ T cells and the ability to kill human tumor cells expressing WT1. There have been several prior clinical studies in humans using parts of the WT1 gene, notably as peptide vaccine candidates, demonstrating the production of modest levels of CD8+ T-cell responses and measurable clinical responses, although both effects were transient. This is the first study to combine DNA vaccination with electroporation delivery of WT1 antigens with the goal of stimulating high and durable levels of immune responses, which are considered critical for improving clinical outcomes.

More Information

WT1 Therapeutic Leukemia DNA Vaccine

Leukemia is a malignant cancer of bone marrow and blood characterized by the uncontrolled accumulation of blood cells. Leukemia accounts for at least 300,000 new cases and 222,000 deaths worldwide each year - a very high death rate. Wilms' Tumor gene 1 (WT1) is overexpressed in 70-90% of acute leukemias, which led the University of Southampton to design its leukemia DNA vaccine to target this antigen.

Acute myeloid leukemia (AML), the most common acute leukemia affecting adults, is treated with chemotherapy. The five-year survival rate is 40%. As an acute leukemia, AML is characterized by a rapid increase in the numbers of immature blood cells. The resultant crowding renders the bone marrow unable to produce healthy blood cells. Immediate treatment is required due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body.

Chronic myeloid leukemia (CML) is characterized by the excessive buildup of relatively mature, but still abnormal, white blood cells. These cells are produced at a much higher rate than normal, resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms typically take months or years to progress and so are sometimes monitored for some time before treatment to ensure maximum therapeutic efficacy.

Standard of care for newly diagnosed CML patients is imatinib; the five-year survival rate is 90%. In a more advanced, uncontrolled state, when the patient cannot tolerate imatinib, or if the patient wishes to attempt a permanent cure, then an allogeneic bone marrow transplantation may be performed. This procedure involves high-dose chemotherapy and radiation followed by infusion of bone marrow from a compatible donor. Approximately 30% of patients die from this procedure.