PILOT STUDY OF DOSE INTENSIFIED PROCARBAZINE, CCNU, VINCRISTINE FOR BRAIN TUMORS

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Patients with newly diagnosed "poor prognosis" brain tumors and patients with recurrent brain tumors who have received no prior chemotherapy and no craniospinal radiation therapy will treated with 4 courses of time compressed chemotherapy composed of Procarbazine, CCNU and Vincristine (PCV). Peripheral blood stem cells will be collected by an apheresis procedure prior to treatment and given back to the patient following each course of chemotherapy. To increase the tolerablility of the marrow to the chemotherapy drugs, we propose to collect a portion of the peripheral blood stem cells from which the CD34+ cells will be separated and transduced with the human O6-methylguanine DNA methyltransferase (MGMT) c DNA in the retrovirus construct, PGK-MGMT. These cells, will be given back to the patient following chemotherapy courses, along with unmanipulated stem cells, after course #4. Only unmanipulated stem cells will be given back to the patient following courses #2 and #3. This is a non-myeloablative protocol and the infusion of large number of unmanipulated mononuclear cells during each cycle minimizes the risk of poor engraftment. The primary objectives include the following 1) to determine toxicity associated with infusion of CD34+ derived cells transduced with a retroviral vector expressing O6-methylguanine DNA methyltransferase; 2) to determine the safety of genetic modification of cells carried out in the presence of recombinant fibronectin fragment, CH-296, utilized to assist in retroviral entry into mammalian cells; 3) to determine any evidence of engraftment of cells exposed to CH-296 during retroviral transduction; 4) to determine evidence of antibodies to FN following infusion of cells exposed to CH-296 during ex vivo retroviral transduction.