16 Participants Needed

Stem Cell Rescue Therapy for Glioblastoma

(hSTAR GBM Trial)

Recruiting at 1 trial location
EP
CM
MB
Overseen ByMelissa Bratley, RN
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Leland Metheny
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have had prior chemotherapy for glioblastoma and that post-operative steroids should be tapered to a certain level before enrollment.

What data supports the effectiveness of the drug combination used in the Stem Cell Rescue Therapy for Glioblastoma?

Research shows that temozolomide (TMZ) has high response rates in treating certain brain tumors, and combining carmustine (BCNU) with O6-benzylguanine (BG) has been studied for its activity in treating resistant malignant gliomas. These findings suggest potential effectiveness in glioblastoma treatment.12345

Is Stem Cell Rescue Therapy for Glioblastoma safe for humans?

Research shows that treatments involving carmustine (BCNU) and temozolomide (TMZ) can cause myelosuppression (a decrease in bone marrow activity leading to fewer blood cells) as a significant side effect. The combination of these drugs has been tested in humans, and while it is feasible, it may lead to blood-related toxicities, especially with long-term use.46789

What makes the Stem Cell Rescue Therapy for Glioblastoma unique?

This treatment is unique because it combines gene therapy with chemotherapy, using a modified gene (MGMT-P140K) to protect healthy cells from the toxic effects of chemotherapy drugs like Carmustine and Temozolomide, allowing for higher doses to be used against the tumor while reducing side effects.48101112

What is the purpose of this trial?

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.

Research Team

Leland Metheny | Case Comprehensive ...

Leland Metheny, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults aged 18-70 with newly diagnosed, supratentorial glioblastoma or gliosarcoma who've had a significant portion of their tumor surgically removed. They should have an expected survival of at least 12 weeks, be in good physical condition (ECOG 0-1 or Karnofsky ≥70), and not have received prior chemotherapy for GBM. Participants must not have certain genetic mutations (unmethylated MGMT without IDH1/IDH2 mutation) and should be stable enough to undergo an autologous transplant.

Inclusion Criteria

Negative screening for Hepatitis B, C, and HIV
Patient must be considered clinically stable
I can provide 10 slides or a sample of my tumor for testing.
See 14 more

Exclusion Criteria

I have been cancer-free or in remission for at least 2 years.
Inability to undergo repeated MRI evaluation or allergy to Gadolinium-containing contrast agent
Active illicit drug use or diagnosis of alcoholism
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive 6 weeks of standard of care radiotherapy

6 weeks

Stem Cell Mobilization

Participants undergo stem cell mobilization after radiation therapy

2-4 weeks

Chemotherapy

Participants receive chemotherapy with O6-benzylguanine, temozolomide, and carmustine

Variable, based on dose escalation

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

  • Carmustine
  • Filgrastim
  • O6-benzylguanine
  • P140K-MGMT
  • Photon Based Radiotherapy
  • Temozolomide
Trial Overview The study tests the effectiveness of P140K MGMT hematopoietic stem cells combined with O6-benzylguanine, temozolomide, and carmustine chemotherapy on patients post-surgery. It aims to make bone marrow more resistant to chemo so higher doses can target tumor cells while sparing the bone marrow.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: stem cell mobilization after radiation therapyExperimental Treatment6 Interventions
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.

Carmustine is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as BiCNU for:
  • Brain tumors
  • Multiple myeloma
  • Hodgkin's disease
  • Non-Hodgkin's lymphoma
🇪🇺
Approved in European Union as Carmubris for:
  • Brain tumors
  • Multiple myeloma
  • Hodgkin's disease
  • Non-Hodgkin's lymphoma
🇨🇦
Approved in Canada as BCNU for:
  • Brain tumors
  • Multiple myeloma
  • Hodgkin's disease
  • Non-Hodgkin's lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Leland Metheny

Lead Sponsor

Trials
6
Recruited
80+

Andrew Sloan, MD

Lead Sponsor

Trials
2
Recruited
90+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a phase II trial involving 38 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a high response rate, with 52.6% of patients showing a complete or partial response, indicating its efficacy as a first-line chemotherapy.
TMZ was generally well tolerated, with hematologic side effects being the most common, and only one patient discontinuing treatment due to toxicity, suggesting a favorable safety profile for chemotherapy-naive patients.
Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971.van den Bent, MJ., Taphoorn, MJ., Brandes, AA., et al.[2022]
The novel compound EPIC-0307 enhances the effectiveness of temozolomide (TMZ) in treating glioblastoma by inhibiting DNA damage repair proteins and reducing the expression of MGMT, a key factor in TMZ resistance.
EPIC-0307 works by disrupting the PRADX-EZH2 interaction, which leads to increased expression of tumor suppressor genes and promotes cell cycle arrest and apoptosis in GBM cells, thereby restoring sensitivity to TMZ.
EPIC-0307-mediated selective disruption of PRADX-EZH2 interaction and enhancement of temozolomide sensitivity to glioblastoma via inhibiting DNA repair and MGMT.Xin, L., Tan, Y., Zhu, Y., et al.[2023]
In a phase II trial involving 32 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a 25% objective response rate, indicating its potential as an effective second-line treatment after PCV chemotherapy.
TMZ was generally well tolerated, with hematological side effects being the most common, and a median time to progression of 8 months for those who responded, suggesting it could be a viable option for patients who do not respond to initial treatments.
Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972.van den Bent, MJ., Chinot, O., Boogerd, W., et al.[2020]

References

Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. [2022]
EPIC-0307-mediated selective disruption of PRADX-EZH2 interaction and enhancement of temozolomide sensitivity to glioblastoma via inhibiting DNA repair and MGMT. [2023]
Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. [2020]
Thresholds of O6-alkylguanine-DNA alkyltransferase which confer significant resistance of human glial tumor xenografts to treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea or temozolomide. [2018]
Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma. [2021]
[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. [2018]
Phase I trial of carmustine plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. [2017]
Hematopoietic expression of O(6)-methylguanine DNA methyltransferase-P140K allows intensive treatment of human glioma xenografts with combination O(6)-benzylguanine and 1,3-bis-(2-chloroethyl)-1-nitrosourea. [2020]
Phase 1 study of 28-day, low-dose temozolomide and BCNU in the treatment of malignant gliomas after radiation therapy. [2018]
In vivo selection of autologous MGMT gene-modified cells following reduced-intensity conditioning with BCNU and temozolomide in the dog model. [2021]
MGMT-inhibitor in combination with TGF-βRI inhibitor or CDK 4/6 inhibitor increases temozolomide sensitivity in temozolomide-resistant glioblastoma cells. [2021]
12.United Statespubmed.ncbi.nlm.nih.gov
Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients. [2021]
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