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

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

DRUG

O6-benzylguanine

O6BG is a low molecular-weight purine analog which selectively and irreversibly inactivates the DNA-repair enzyme, O6- alkylguanine DNA-alkyltransferase.

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

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Leland Metheny

  lead OTHER

Principal Investigators

• Leland Metheny, MD · University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-01-20

Primary Completion

2026-06-01

Completion

2026-12-01

FDA Drug

Yes

Countries

• United States

Study Locations