NCT05052957

hSTAR GBM (Hematopoetic Stem Cell (HPC) Rescue for GBM)

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: Leland Metheny · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Glioblastoma Multiforme
• Glioblastoma Multiforme, Adult
• Supratentorial Glioblastoma
• Supratentorial Gliosarcoma

Interventions

Type	Name	Description
BIOLOGICAL	P140K-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
DRUG	O6-benzylguanine	O6BG is a low molecular-weight purine analog which selectively and irreversibly inactivates the DNA-repair enzyme, O6- alkylguanine DNA-alkyltransferase.
RADIATION	Photon 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.
DRUG	temozolomide	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
DRUG	Filgrastim	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.
DRUG	carmustine	BCNU is a lipid soluble agent which has alkylating properties, plus an isocyanate metabolite which interferes with DNA and RNA synthesis.

Timeline

• Start date: 2023-01-20
• Primary completion: 2026-06-01
• Completion: 2026-12-01
• First posted: 2021-09-22
• Last updated: 2025-11-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study