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

NCT05052957 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CASE53201U01CA236215-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (3)

• Percent of participants able to complete treatment

  To evaluate and compare the feasibility of introducing and expressing P140K MGMT cDNA using a lentiviral-based provirus in autologous hematopoietic stem cells harvested from newly diagnosed IDH-1 WT GBM with unmethylated MGMT promoter using two different sequences of stem cell mobilization. 1\. What percent of patients who enter trial can complete treatment.

  10 years after start of study

• Incidence of adverse events

  proportion of participants experiencing a grade 3 or higher AE/SAE

  Up to 30 days post-treatment

• Overall Survival

  Median overall survival in months.

  Up to 15 years post-treatment

Secondary Outcomes (5)

• Myelosuppression

  5 years

• Detection of P140K transduced BG and TMZ resistant cells

  5 years

• Enrichment of P140K-MGMT

  5 years

• Tumor Response using imaging

  5 years

• PFS using imaging

  5 years

Study Arms (1)

stem cell mobilization after radiation therapy

EXPERIMENTAL

Participants at University Hospitals-Seidman Cancer Center (UH-SCC) will receive stem cell mobilization after 6 weeks of standard of care (SOC) radiotherapy. Followed by SOC chemotherapy.

Biological: P140K-MGMT; Drug: O6-benzylguanine; Radiation: Photon Based Radiotherapy; Drug: temozolomide; Drug: Filgrastim; Drug: carmustine

Interventions

P140K-MGMT BIOLOGICAL

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

stem cell mobilization after radiation therapy

O6-benzylguanine DRUG

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

Also known as: BG

stem cell mobilization after radiation therapy

Photon Based Radiotherapy RADIATION

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.

stem cell mobilization after radiation therapy

temozolomide DRUG

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

Also known as: TMZ

stem cell mobilization after radiation therapy

Filgrastim DRUG

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.

Also known as: G-CSF,Granulocyte-Colony Stimulating Factor

stem cell mobilization after radiation therapy

carmustine DRUG

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

Also known as: BCNU,bis-chloronitrosourea

stem cell mobilization after radiation therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 IDH1 or IDH2mutation on tumor tissue by a CLIA-approved immunohistochemistry or DNA sequencing test on local testing
• Patients aged 18-75 years.
• ECOG performance status 0-1or Karnofsky ≥ 70.
• No myelosuppressive chemotherapy or hematopoietic cell transplantation prior to the diagnosis of GBM and no prior chemotherapy (including Gliadel BCNU wafers) for GBM
• Life expectancy of at least 12 weeks.
• No plan for hypofractionated radiation therapy
• Adequate hematologic (absolute neutrophil count (ANC)≥ 1000/mm3, platelets ≥ 100,000/mm3, Hgb ≥ 9.5, hepatic (Bilirubin ≤ 2.0 mg/dl, AST and ALT less than or equal to 3 times institutional upper limit of normal, prothrombin time \<1.2 times normal), and renal (serum creatinine ≤ 2.0 mg/dl or Creatinine Clearance ≥ 60mL/min/1.73 m2for subjects with serum creatinine levels above institutional normal). These tests will be repeated within 2 weeks of treatment with BG and TMZ, and must meet the same criteria. -Post-operative steroids are i) tapered to ≤ 8mg dexamethasone/day(or equivalent)and ii) patient has been on a stable or decreasing steroid dose for the 7 days prior to enrollment
• Patients of child-bearing potential must agree to using single barrier contraception.
• Must be willing and able to understand provide informed consent.
• Patient must have all sutures removed prior to registration
• Patient must be considered to be clinically stable.
• The subject will be identified as a candidate for an autologous transplant via an evaluation by a transplant physician per standard of care. Participants will be screened by their transplant physician and social work for a history of substance abuse per screening tool such as SIPAT. Any participant with positive screen for significant substance abuse will undergo evaluation and must have a treatment, management plan in place and must have formal review of medical team prior to initiation of transplant procedures.
• No evidence of active infection.

You may not qualify if:

• Any known medical or hereditary condition associated with immunosuppression;orothermedical illness which may jeopardize patient safety.
• Pregnant or lactating women. There is data to indicate that BCNU and TMZ is teratogenic and carcinogenic. Thus, its use in pregnant women would confer unnecessary risk to the fetus.
• Patients with symptomatic pulmonary disease and other severe co-morbid respiratory conditions, including patients with active pulmonary infection and/or pulse oximetry \< 90% and a corrected DLCO \< 50% of predicted. However, subjects with a corrected DLCO in the range of 50-70% should have Pulmonologyclearance prior to intervention.
• Patients with known diagnosis heart failure or cardiac insufficiency and an LVEF of \< 40%. History of acute coronary event including MI within 6 months prior to study enrollment.
• Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmiaor bradycardia.Inability to undergo repeated MRI evaluation; or allergy or intolerance of Gadolinium-containing contrast agent.
• Active illicit drug use or diagnosis of alcoholism.
• Prior diagnosis of any malignant disease with the exception of non-melanomatous skin cancer, or carcinoma in situof the cervix, bladder, prostate, or breast, unless patient has been disease-free/in remission for ≥2 years prior to date of study enrollment.
• Mental incapacity or psychiatric illness preventing informed consent.
• History of Hepatitis B or C or Hepatitis grade ≥3 are excluded due to the potential for additional hepatotixicity

Sponsors & Collaborators

• Leland Metheny: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

O(6)-benzylguanine; Temozolomide; Filgrastim; Carmustine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds

Study Officials

• Leland Metheny, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Bratley, RN

CONTACT

1-800-641-2422; CTUreferral@uhhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: September 22, 2021
• Study Start: January 20, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Investigators who provide a methodologically sound proposal for use of requested data.

Locations

US (1)