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; Supratentorial Glioblastoma; Supratentorial Gliosarcoma; Glioblastoma Multiforme, Adult

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

You may qualify if:

• Participants with histologically confirmed, newly diagnosed, supratentorial glioblastoma or gliosarcoma who have undergone tumor resection are eligible up to 35 days postoperatively. Participants with primarily infratentorial disease, or with multifocal, or leptomeningeal dissemination of disease will be excluded. In general, participants will not have \> 1 cm residual measurable or evaluable disease after surgical tumor resection.
• Participant must have unmethylated MGMT
• Absence of IDH1 or IDH2 mutation on tumor tissue by a CLIA-approved immunohistochemistry or DNA sequencing test on local testing.
• Participants aged 18 years or older.
• ECOG performance status 0-1or Karnofsky ≥ 70.
• Life expectancy of at least 12 weeks.
• No plan for hypofractionated radiation therapy
• Adequate hematologic and hepatic function:
• CBC/differential obtained within 28 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 Note: the use of G-CSF or other intervention to achieve Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 is acceptable)
• Platelets ≥ 50,000 cells/mm3 (Note: the use of transfusion or other intervention to achieve Platelets ≥ 50,000 cells/mm3 is acceptable)
• Hemoglobin ≥ 9.0 g/dl (Note: the use of transfusion or other intervention to achieve Hgb ≥9.0 g/dl is acceptable)
• Adequate hepatic function within 28 days prior to registration:
• Bilirubin ≤ 3 ULN
• ALT and AST ≤ 3 x ULN

You may not qualify if:

• Any known medical or hereditary condition associated with immunosuppression; or other medical illness, which may jeopardize participant 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.
• Participants with a corrected DLCO or FEV1 \< 50% of predicted.
• Participants with known diagnosis heart failure or cardiac insufficiency and an LVEF of \< 40%.
• Inability to undergo repeated MRI evaluation; or allergy or intolerance of Gadoliniumcontaining contrast agent.
• Active illicit drug use or diagnosis of active alcoholism.
• Prior diagnosis of any malignant disease with the exception of non-melanomatous skin cancer, or carcinoma in situ of the cervix, bladder, prostate, or breast, unless the participant has been disease-free/in remission for ≥2 years prior to date of study enrollment.
• Known human immunodeficiency virus infection or acquired immunodeficiency syndrome related illness.
• Serologic status reflecting active hepatitis B or C infection. Individuals that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive individuals will be excluded).

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): November 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: September 10, 2026

Record last verified: 2026-09

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)