DNA vaccine for leukemia


Phase II

  • Acute myeloid leukemia (AML)
  • Chronic myeloid leukemia (CML)

Milestone

Not currently recruiting (due to interruption in sponsor funding)


Leukemia stain

Description
Developed by the University of Southampton with funding from Leukæmia and Lymphoma Research and Cancer Research UK, this DNA vaccine is encoded for Wilms' Tumor gene 1 (WT1), which is highly associated with leukemia. The vaccine is delivered using Inovio’s ELGEN-1000 automated electroporation device.

Development Status
In January 2011, the University of Southampton initiated a phase II clinical trial to evaluate a DNA vaccine encoded for two antigens (p.DOM-WT1-37 and p.DOM-WT1-126) for the treatment of acute and chronic myeloid leukemia (AML and CML).

The study is not currently recruiting new subjects due to an interruption in sponsor funding. Efforts are under way to re-establish funding, however, the study is currently on hold pending the outcome of these refunding efforts. There have been no safety concerns identified during the study.

Disease State

Leukemia is a malignant cancer of bone marrow and blood characterized by the uncontrolled accumulation of blood cells.

AML, a cancer of the myeloid line of blood cells, is characterized by rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults; its incidence increases with age. Only about one-third of those between ages 18-60 who are diagnosed with AML can be cured. With conventional chemotherapy, 70% of the patients in the group under study will relapse within two years, and current therapy is devastating in older adults.

CML is a type of cancer that causes the body to produce large numbers of immature and mature white blood cells (myelocytes). Approximately 85% of patients with CML are in the chronic phase at the time of diagnosis. Ultimately, in the absence of curative treatment, the disease progresses to an accelerated phase where median survival is around three to five years. CML can occur at any age, but it more commonly affects middle-aged and older people.



Clinical Trials

Clinical Trials

WT1 Therapeutic Leukemia DNA Vaccine

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. At this time, however, the study is not recruiting new subjects due to an interruption in sponsor funding. Efforts are under way to re-establish funding, however, the study is currently on hold pending the outcome of these refunding efforts. There have been no safety concerns identified during the study.

Upon the re-establishment of funding, this open-label, multi-center clinical trial would continue to be run by the University of Southampton to evaluate a DNA vaccine to treat chronic myeloid leukemia and acute myeloid leukemia. 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 initially received 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 are molecular responses to a disease marker called BCR-ABL in CML patients and time to disease progression in AML patients. The study is also monitoring 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 is taking 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).

Go to study protocol

Study Data

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

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.