Phase II Trial O6-benzylguanine(BG) and Temozolomide(TMZ) Therapy of Glioblastoma Multiforme (GBM) With Infusion of Autologous P140K MGMT+Hematopoietic Progenitors to Protect Hematopoiesis
Leland Metheny
Summary
This phase II trial studies the effect of P140K MGMT hematopoietic stem cells, O6-benzylguanine, temozolomide, and carmustine in treating participants with supratentorial glioblastoma or gliosarcoma who have recently had surgery to remove most or all of the brain tumor (resected). Chemotherapy drugs, such as 6-benzylguanine, temozolomide, and carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing. Placing P140K MGMT, a gene that has been created in the laboratory into bone marrow making the bone more resistant to chemotherapy, allowing intra-patient dose escalation which kills more tumor cells while allowing bone marrow to survive.
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients with histologically confirmed, newly diagnosed, supratentorial glioblastoma or gliosarcoma who have undergone gross total tumor resection or near gross total resection (resection of \>85% of enhancing tumor demonstrated by MRI) are eligible up to 35 days post-operatively. Patients with primarily infratentorial disease, or with multifocal,or leptomeningeal dissemination of disease will be excluded. In general, patients will not have \> 1 cm residual measurable or evaluable disease after surgical tumor resection. * Patient must have unmethylated MGMT * Absence Of…
Interventions
- BiologicalP140K-MGMT
Ex Vivo Cultured P140K MGMT CD34+ Cells. The transduced cells are a biological product and production is detailed in the Cellular Therapy Lab standard operating procedures and IND 14099
- DrugO6-benzylguanine
O6BG is a low molecular-weight purine analog which selectively and irreversibly inactivates the DNA-repair enzyme, O6- alkylguanine DNA-alkyltransferase.
- RadiationPhoton Based Radiotherapy
Standard of care, photon-based radiotherapy (60Gy in 30 fractions) will be performed in both arms without concomitant TMZ between to 6 weeks post-operatively. Radiotherapy will be performed at UH-SCC.
- Drugtemozolomide
Temozolomide is not directly active but undergoes rapid non-enzymatic conversion at physiologic pHto the reactive compoundMTIC. The cytotoxicity of MTIC is thought to be primarily due to alkylationof DNA. Alkylation (methylation) occurs mainly at the O6 and N7 positions of guanine
- DrugFilgrastim
Filgrastim is a 175 amino acid protein manufactured by recombinant DNA technology. Endogenous filgrastim is a glycoprotein produced by monocytes, fibroblasts, and endothelial cells, which regulates the production of neutrophils within the bone marrow.
Location
- University Hospitals Cleveland Medical CenterCleveland, Ohio