RecruitingPhase 2NCT05052957

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


Sponsor

Leland Metheny

Enrollment

16 participants

Start Date

Jan 20, 2023

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 18 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This study tests an intensive treatment approach for a type of aggressive brain tumor called glioblastoma (GBM). It uses high-dose chemotherapy followed by a rescue of the patient's own blood stem cells to allow the immune system to recover — similar to approaches used in blood cancers — to see if this can improve survival. **You may be eligible if...** - You are 18–75 years old with a newly diagnosed glioblastoma or gliosarcoma that was almost fully removed by surgery - Your tumor has specific genetic features: unmethylated MGMT and no IDH1/IDH2 mutations - You are in good overall health (ECOG 0–1 or Karnofsky ≥70) - Surgery was completed within the past 35 days **You may NOT be eligible if...** - Your tumor is located in the lower part of the brain, is multifocal, or has spread along the brain lining - You have significant residual disease remaining after surgery (>1 cm) - You have major heart, kidney, or other organ problems - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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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.

DRUGcarmustine

BCNU is a lipid soluble agent which has alkylating properties, plus an isocyanate metabolite which interferes with DNA and RNA synthesis.


Locations(1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

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NCT05052957


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