Trial Information

A Phase I Study Investigating Multiple Injections of Autologous CD34+ Derived Dendritic Cells Transduced With an Adenovirus Vector Expressing Inactivated HER-2/Neu in Patients With Metastatic Breast Cancer

Following written, informed consent, consecutive cohorts of 3-6 patients, up to a maximum of
18 patients, will be treated at increasing dose levels based on a modified Fibonacci scheme.
Peripheral blood progenitor cells will be obtained from each patient following cytokine
mobilization (with GM-CSF and G-CSF). Selected CD34+ cells are then cultured with human
GM-CSF, human TNFα, Flt-3 ligand and human interleukin-4. The CD34+ derived dendritic cells
are then transduced with an adenovirus expressing rat HER2/neu. These transduced DCs are
then injected intradermally into the patient. Patients will be injected with the AdHER2/neu
transduced DCs every 21 days for a total of three treatment cycles. The starting dose of
dendritic cells will be 10 X 10^6 DCs. If none of the initial three patients treated at
this dose experiences dose limiting toxicity (DLT) then a new cohort of three patients will
be treated at a second dose level of 50 X 10^6 DCs. If any patient experiences DLT then up
to six patients will be treated at the current dose level; if 2/6 or fewer patients
experience DLT, we will escalate to the to the second dose level. If 3 or more patients
experience DLT, the maximum tolerated dose will be deemed as exceeded and a second cohort of
3 patients will be treated at a 10 fold dose reduction of the initial dose level. The third
dose level will consist of 100 x 10^6 DCs. All treatments will occur in the out-patient
setting and patients will be seen prior to each injection and then monthly for at least
three months following the last injection of AdHER2/neu DCs.