Study of Vaccination With Autologous Acute Myeloblastic Leukemia Cells in Patients With Advanced Myelodysplasia or Acute Myelogenous Leukemia

A Phase I Study of Vaccination With Lethally Irradiated, Autologous Acute Myeloblastic Leukemia Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete Human Granulocyte-Macrophage Colony Stimulating Factor in Patients With Advanced Myelodysplasia or Acute Myelogenous Leukemia

The purpose of this study is to test the safety of a new investigational acute myeloblastic leukemia (AML) vaccine and see what effects (good and bad) it has on patients with advanced myelodysplasia or acute myelogenous leukemia.

This study will make use of leukemic myeloblasts harvested by bone marrow aspirate in patients with myelodysplasia and acute myelogenous leukemia. These harvested tumor cells will be modified by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor (GM-CSF).

Patients will be administered vaccines at one of three dose levels (as determined by total cell yield). Vaccinations will be given weekly for three weeks, followed by every other week until the vaccine supply is exhausted or when patients are removed from the study.

The patient will receive a minimum of six vaccinations, but more will be administered if the vaccine is available.

During the course of the study, patients will be tested to see how their immune system is reacting to the vaccinations. Testing will include bloodwork evaluating the immune cells in the body at monthly intervals. Skin biopsies may also be performed to see if an immune reaction is occuring at the injection site.

During the first course of treatment, a bone marrow biopsy and aspirate may be performed monthly.

The length of time on this study depends upon the number of vaccines available and whether or not unacceptable side effects occur.

Inclusion Criteria:

• Patients must have pathologically documented myelodysplasia or acute myelogenous leukemia.
• The patients with myelodysplasia must also have: French-American-British (FAB) subtype refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T), or normal or hypercellular bone marrow.
• The patients with acute myelogenous leukemia must also: not be candidates for myelosuppressive chemotherapy due to age or comorbid disease, or have relapsed acute myelogenous leukemia or be refractory to standard therapy and not likely to require cytoreductive therapy within 60 days
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Estimated life expectancy of 6 months or greater.
• Age at least 18 years.
• Greater than 4 weeks from any chemotherapy, radiotherapy, immunotherapy, or systemic glucocorticoid therapy (non-glucocorticoid hormonal therapy allowed).
• Greater than 2 months following bone marrow or peripheral blood stem cell transplantation or treatment with donor lymphocyte infusion (DLI).

Exclusion Criteria:

• Uncontrolled active infection.
• Pregnancy or nursing mothers.
• Previous participation in an adenovirus based trial.
• The patients with myelodysplasia who have either: FAB subtype refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), chronic myelomonocytic leukemia (CMML), or the presence of hypocellular bone marrow.
• Chemotherapy, radiotherapy, immunotherapy, or systemic steroid therapy within the last 4 weeks.
• Active central nervous system (CNS) disease.
• Evidence of infection with the human immunodeficiency virus.
• Active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely.