ERC1671 + GM-CSF + Cyclophosphamide for Glioblastoma

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Epitopoietic Research Corporation

Must not be taking: Immunosuppressants, Bevacizumab

Disqualifiers: Metastatic disease, Active infection, Uncontrolled hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 28 days per cycle, repeated until disease progression or intolerance

84 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II clinical trial studies how well ERC1671 plus Granulocyte-macrophage colony-stimulating factor (GM-CSF) plus Cyclophosphamide with Bevacizumab works compared to Placebo Injection plus Placebo Pill with Bevacizumab in treating patients with recurrent/progressive, bevacizumab naïve glioblastoma multiforme and gliosarcoma (World Health Organization (WHO) grade IV malignant gliomas, GBM).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that patients taking temozolomide can start the study treatment 23 days after their last dose. For other chemotherapy drugs, treatment can start as long as side effects are mild. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment ERC1671 + GM-CSF + Cyclophosphamide for Glioblastoma?

Research shows that cyclophosphamide, when used with GM-CSF, has been active against malignant brain tumors, including gliomas. Additionally, GM-CSF is involved in the growth regulation of gliomas, suggesting it plays a role in tumor progression and could be a target for therapy. ^{1 2 3 4 5}

Is the treatment ERC1671 + GM-CSF + Cyclophosphamide generally safe for humans?

Cyclophosphamide has shown acceptable safety in treating glioblastoma, with common side effects being blood-related issues like low white blood cell counts, which can lead to infections. GM-CSF (sargramostim) has been used safely in adults, but there are reports of rare allergic reactions. Overall, these components have been used in humans with manageable safety profiles. ^{6 7 8 9 10}

What makes the ERC1671 + GM-CSF + Cyclophosphamide treatment unique for glioblastoma?

This treatment is unique because it combines ERC1671, a novel immunotherapy, with GM-CSF (a protein that stimulates the immune system) and Cyclophosphamide (a chemotherapy drug) to potentially enhance the body's immune response against glioblastoma, a type of brain cancer. This combination aims to leverage both the immune-stimulating effects of GM-CSF and the cancer-fighting properties of Cyclophosphamide, offering a new approach compared to traditional treatments. ^{1 3 11 12 13}

Research Team

Daniela A. Bota, MD, PhD

Principal Investigator

University of California, Irvine

Eligibility Criteria

This trial is for adults over 18 with glioblastoma or gliosarcoma who are experiencing their first or second relapse. They must have had prior surgery, radiation, and chemotherapy with temozolomide, be in good physical condition (KPS ≥ 70%), and have a life expectancy of more than 12 weeks. Participants should not currently have severe treatment-related side effects except hair loss and certain blood conditions.

Inclusion Criteria

MRI record must show specific timing in relation to prior treatments

I am 18 years old or older.

Life expectancy > 12 weeks

Exclusion Criteria

I haven't had any major abdominal issues like fistula, perforation, or abscess in the last 6 months.

I have had a heart problem recently.

I haven't taken immunosuppressive drugs in the last 2 weeks, except for dexamethasone for brain swelling.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ERC1671, GM-CSF, and cyclophosphamide in combination with bevacizumab or placebo controls in 28-day cycles

28 days per cycle, repeated until disease progression or intolerance

Every 2 weeks for bevacizumab administration

Follow-up

Participants are monitored for safety, effectiveness, and immune response after treatment

12 months

Every 6 weeks for radiographic assessment

Treatment Details

Interventions

• Cyclophosphamide
• ERC1671
• GM-CSF

Trial Overview The study tests if ERC1671 combined with GM-CSF and Cyclophosphamide improves outcomes when added to Bevacizumab compared to placebo injections/pills plus Bevacizumab in patients with recurrent/progressive glioblastoma multiforme that haven't been treated with Bevacizumab before.

Participant Groups

Group I: (ERC1671/GM-CSF/Cyclophosphamide)+bevacizumab/bevacizumab biosimilar Experimental Treatment 4 Interventions

ERC1671 and GM-CSF will be intradermally administered, while cyclophosphamide is orally administered. GM-CSF dose is 500mcg fixed dose and cyclophosphamide dose is 50 mg/day. Bevacizumab or approved bevacizumab biosimilars are administered as standard of care at 10 mg/kg every 2 weeks. The treatment will be repeated every 28 days until progression of disease or intolerance.

Group II: (Placebo Injection/Placebo Pill) +Bevacizumab/bevacizumab biosimilar Placebo Group 3 Interventions

The control group will have the same study schedule except that the patients will be receiving the Oral Control on the Cyclophosphamide treatment days and the Injectable control on the GM-CSF + ERC1671 treatment days. The control group will receive bevacizumab or approved bevacizumab biosimilar just as the active treatment group above. The treatment will be repeated every 28 days until progression of disease or intolerance.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Epitopoietic Research Corporation

Lead Sponsor

Trials

2

Recruited

110+

University of California, Irvine

Collaborator

Trials

580

Recruited

4,943,000+

Findings from Research

A high-dose intensity regimen of cyclophosphamide combined with GM-CSF was tested in 23 children with brain tumors, showing partial responses in 5 out of 6 patients with primitive neuroectodermal tumors (PNET), but no effectiveness against malignant glioma.

The treatment resulted in a manageable safety profile, with a short duration of severe neutropenia, although fever during neutropenia was common, occurring in 54 out of 83 treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors. Abrahamsen, TG., Lange, BJ., Packer, RJ., et al.[2020]

In a study involving 35 patients (18 receiving GM-CSF and 17 controls), GM-CSF did not enhance T cell or natural killer cell recovery after allogeneic stem cell transplantation, contrary to expectations.

However, GM-CSF administration improved dendritic cell reconstitution in patients undergoing autologous stem cell transplantation, suggesting its benefits may vary based on the type of transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. Eksioglu, EA., Kielbasa, J., Eisen, S., et al.[2018]

A case report described an adverse reaction to sargramostim (rhu GM-CSF) involving symptoms like itching, hives, and throat tightness, highlighting the potential for allergic reactions to this treatment.

Prick skin testing showed that the patient was sensitized to sargramostim but not to filgrastim (rhu G-CSF), suggesting that skin testing could help identify patients at risk for allergic reactions to GM-CSF therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate hypersensitivity to human recombinant granulocyte-macrophage colony-stimulating factor associated with a positive prick skin test reaction. Engler, RJ., Weiss, RB.[2017]

Mecapegfilgrastim, a long-acting granulocyte colony-stimulating factor, significantly reduced the duration of severe neutropenia in breast cancer patients undergoing chemotherapy compared to filgrastim, with mean durations of 1.06 days and 2.06 days respectively.

Both dosing regimens of mecapegfilgrastim (100 µg/kg and a fixed 6 mg dose) were well tolerated and showed comparable efficacy, making the fixed 6 mg dose a convenient option for patients due to its once-per-cycle administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mecapegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer: a randomized, multicenter, active-controlled phase III trial. Xu, F., Zhang, Y., Miao, Z., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor in human gliomas with tumor progression. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor as an autocrine survival-growth factor in human gliomas. [2012]

4. United States pubmed.ncbi.nlm.nih.gov

CSF-1R inhibition alters macrophage polarization and blocks glioma progression. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid cells through interleukin-4 receptor-α. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Use of GM-CSF in children after high-dose chemotherapy. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Evaluation of pre-radiotherapy cyclophosphamide in patients with newly diagnosed glioblastoma multiforme. Writing Committee for The Brain Tumor Center at Duke. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Immediate hypersensitivity to human recombinant granulocyte-macrophage colony-stimulating factor associated with a positive prick skin test reaction. [2017]

10. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mecapegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer: a randomized, multicenter, active-controlled phase III trial. [2022]

11. Greece pubmed.ncbi.nlm.nih.gov

Cerebral ventricular fluid distribution of subcutaneous granulocyte-macrophage colony stimulating factor. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor and B7-2 combination immunogene therapy in an allogeneic Hu-PBL-SCID/beige mouse-human glioblastoma multiforme model. [2017]

13. United States pubmed.ncbi.nlm.nih.gov

Activity of high-dose cyclophosphamide in the treatment of childhood malignant gliomas. [2019]