Trial Information

A Pilot Study of Dose-Intensified Procarbazine, CCNU, Vincristine (PCV) for Poor Prognosis Pediatric and Adult Brain Tumors Utilizing Fibronectin-Assisted, Retroviral-Mediated Modification of CD34+ Peripheral Blood Cells With O6-Methylguanine DNA Methyltransferase

OBJECTIVES: I. Determine the toxicity (detection of replication competent retrovirus)
associated with CD34+ cells transduced with a retroviral vector expressing human
O6-methylguanine DNA methyltransferase in adult and pediatric patients with poor prognosis
CNS tumors. II. Determine the safety of genetic modification of cells carried out in the
presence (ex vivo) of recombinant fibronectin (FN) fragment utilized to assist in retroviral
entry into mammalian cells. III. Determine any evidence of engraftment of cells exposed to
FN during retroviral transduction. IV. Determine any evidence of antibodies to FN following
infusion of cells exposed to FN during ex vivo retroviral transduction.

OUTLINE: Patients with surgically approachable lesions undergo maximal surgical debulking
that allows preservation of good neurologic functioning. Harvest: Patients receive
filgrastim (G-CSF) subcutaneously or IV beginning 4 days prior to initiation of first
leukapheresis and continuing until completion of harvest. Peripheral blood stem cells are
harvested and selected for CD34+ cells which are transduced with a fibronectin assisted
retroviral vector expressing human O6-methylguanine DNA methyltransferase. Intensification:
Patients receive oral lomustine and vincristine IV on day 0 and oral procarbazine on days
1-7. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or
unacceptable toxicity. Patients with newly diagnosed tumors may undergo involved field
radiotherapy (IF-RT) after completion of the third course of chemotherapy and may begin the
fourth course of chemotherapy after completion of IF-RT. Transplantation: Two-thirds of the
transduced CD34+ cells are reinfused on day 9 of the first course of chemotherapy. The
remaining portion (one-third) of the transduced CD34+ cells are reinfused on day 9 of the
second course of chemotherapy. Untransduced CD34+ cells are reinfused on day 9 of the last 3
courses of chemotherapy. Patients are followed every 3 months for 6 months, every 4 months
for 1 year, every 6 months through year 5, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 15-20 patients will be accrued for this study within 1
year.