Recruiting
Phase 2

HPC Rescue

Sponsor:

Leland Metheny

Code:

NCT05052957

Conditions

Glioblastoma Multiforme

Glioblastoma Multiforme, Adult

Supratentorial Glioblastoma

Supratentorial Gliosarcoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

P140K-MGMT

O6-benzylguanine

Photon Based Radiotherapy

temozolomide

Filgrastim

Study Details

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

Study ID

NCT05052957

Start date

Jan 20, 2023

Status verified date

Sep, 2026

Completion date

Mar 1, 2027

Anticipated

Primary completion date

Nov 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • Participants of child-bearing potential must agree to use single barrier contraception from time of trial entry to completion of the last cycle of chemotherapy.
  • Must be willing and able to understand and provide informed consent.
  • Participant must be considered to be clinically stable.
  • The participant will be identified as a candidate for an autologous transplant via an evaluation by a transplant physician per standard of care.
  • No evidence of active infection.
  • Participant must have the ability to understand and willingness to sign an informed consent document.

Exclusion Criteria:

  • 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).

Study Design

Enrollment

16 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: stem cell mobilization after radiation therapy

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.

Interventions

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

O6-benzylguanine

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

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.

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

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.

carmustine

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

Primary outcome measure

  • Percent of participants able to complete treatment [ Time Frame: 10 years after start of study ]
  • Incidence of adverse events [ Time Frame: Up to 30 days post-treatment ]
  • Overall Survival [ Time Frame: Up to 15 years post-treatment ]

Central Contacts and Locations

Central contacts

Melissa Bratley, RN

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

Locations

University Hospitals Cleveland Medical Center

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Leland Metheny, MD

216-844-0130Leland.metheny@uhhospitals.org

More Information

Sponsor

Leland Metheny

Last update posted

Sep 10, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Leland Metheny on 2026-09-10. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.