G-CSF for Glioblastoma

Overseen By Jorg Dietrich, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Temozolomide

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, HIV, Sickle cell, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study involves the study of granulocyte colony stimulating factor (G-CSF) in patients with MGMT-methylated glioblastoma multiforme (GBM) that are undergoing standard chemoradiation. The study aims to evaluate G-CSF's effects on brain health and cognitive function. The name of the study drugs involved in this study are: * G-CSF (also called Filgrastim) * Temozolomide (TMZ), a standard of care chemotherapy drug

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on high doses of corticosteroids, you may need to taper down to a lower dose before starting the trial.

What data supports the effectiveness of the drug G-CSF for treating glioblastoma?

G-CSF drugs like Filgrastim (Neupogen) are effective in reducing the risk of neutropenia (a low level of white blood cells) caused by chemotherapy in cancer patients, which helps them continue their treatment without interruption. While this data is from studies on other cancers, it suggests that G-CSF can support patients undergoing chemotherapy by boosting their immune system. ^{1 2 3 4 5}

Is G-CSF safe for use in humans?

G-CSF, including versions like Filgrastim and Neupogen, has been widely used and studied for safety in humans, particularly in patients undergoing chemotherapy. Common side effects include bone pain, muscle pain, and weakness, but serious side effects are rare. Overall, it is considered safe for use in supportive cancer care. ^{1 2 6 7 8}

How does the drug G-CSF differ from other treatments for glioblastoma?

G-CSF (granulocyte colony-stimulating factor) is unique because it is primarily used to boost white blood cell counts in patients undergoing chemotherapy, which is different from typical glioblastoma treatments that focus on directly targeting the tumor. This approach may offer a novel way to support the immune system during cancer treatment. ^{1 2 4 9 10}

Research Team

Jorg Dietrich

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed glioblastoma multiforme (GBM), WHO grade 4, IDH wildtype. They must have a positive MGMT promoter methylation status, good performance status (KPS > 60), and life expectancy over 6 months. Patients need to be able to undergo standard chemoradiation therapy and brain MRIs. Exclusions include pregnancy, other investigational drugs use, severe infections or HIV/AIDS, prior cranial irradiation, certain allergies, non-English/Spanish speakers due to cognitive testing requirements.

Inclusion Criteria

I am set to undergo a 6-week radiation therapy and 6 months of chemotherapy with temozolomide.

I have another cancer, but it won't affect this trial's treatment.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I am not pregnant, as the treatment in this study could harm a pregnancy.

Participants who are receiving any other investigational agents

I do not have any severe infections or HIV that could affect my white blood cell count.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Chemoradiation

Participants undergo a 6-week chemoradiation (chemo-RT) cycle followed by a 4-week break

10 weeks

Weekly visits during chemoradiation

G-CSF Treatment

Participants receive G-CSF during the 4-week break and during up to 6 additional 4-week cycles of chemotherapy

7 months

Monthly visits for G-CSF administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits every 2 months

Treatment Details

Interventions

• G-CSF

Trial Overview The study tests the effects of granulocyte colony stimulating factor (G-CSF) on brain health and cognitive function in GBM patients undergoing standard chemoradiation therapy. G-CSF is given alongside Temozolomide chemotherapy during a planned course of radiation treatment.

Participant Groups

Group I: Standard Chemoradiation combined with G-CSF Experimental Treatment 2 Interventions

Per standard of care, participants undergo a 6-week chemoradiation (chemo-RT) cycle followed by a 4-week break. During this 4-week break after chemo-RT, participants receive granulocyte colony stimulating factor (G-CSF) once per day for 5 days (Days 7-11). After the 4-week break, as a part of standard care, participants may then receive up to 6 additional 4-week cycles of chemotherapy (temozolomide (TMZ)). During these additional TMZ cycles, participants will receive G-CSF once per day for 3 consecutive days (Days 14-16). G-CSF is injected under the skin (subcutaneously injected) by a study staff member, or self-administered (or a caregiver) can be trained by a study staff member to administer it at home. The chemo-RT (radiation therapy and chemotherapy (TMZ)) are standard of care in this study.

Group II: Standard Chemoradiation Experimental Treatment 1 Intervention

Participants receive standard of care chemoradiation (chemo-RT) which includes an initial 6-week chemo-RT cycle followed by a 4-week break, and up to 6 additional 4-week chemotherapy (temozolomide (TMZ)) cycles.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

In a study involving 348 breast cancer patients undergoing chemotherapy, the new G-CSF XM02 was found to significantly reduce the duration of severe neutropenia compared to a placebo, with a mean duration of 1.1 days for both XM02 and Neupogen, versus 3.9 days for placebo.

XM02 demonstrated similar safety profiles to Neupogen, indicating that it is an effective alternative for managing chemotherapy-induced neutropenia without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. del Giglio, A., Eniu, A., Ganea-Motan, D., et al.[2022]

Pegfilgrastim is as effective or even more effective than filgrastim in reducing chemotherapy-induced neutropenia, making it a strong option for patients undergoing cancer treatment.

One of the key benefits of pegfilgrastim is that it can be administered just once per chemotherapy cycle, which may improve patient compliance and enhance their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegfilgrastim; a neutrophil mediated granulocyte colony stimulating factor-expanding uses in cancer chemotherapy. Morishita, M., Leonard, RC.[2022]

In a study involving 31 patients with breast cancer and ovarian carcinoma, the recombinant human G-CSF-Leukostim (filgrastim) effectively treated or prevented chemotherapy-induced neutropenia after just 2-6 injections.

Leukostim allowed 5 breast cancer patients to undergo an additional 10 cycles of chemotherapy without inhibiting blood cell production, and no adverse side effects were reported, indicating its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of Leukostim, a Russian preparation of granulocyte colony-stimulating factor, in the treatment of chemotherapy-induced neutropenia in patients with malignant tumors]. Korman, DB., Boronovskaia, LE., Maslova, IA., et al.[2015]

Tbo-filgrastim, a recombinant human G-CSF, has been shown to be as effective as Neupogen in reducing the duration of severe neutropenia in patients undergoing myelosuppressive chemotherapy, based on data from three phase III studies involving 677 patients.

The safety profile of tbo-filgrastim is comparable to Neupogen, with most adverse events related to chemotherapy rather than the drug itself, and only a small percentage of patients experiencing severe drug-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety of tbo-filgrastim, a short-acting human granulocyte colony-stimulating factor. Pettengell, R., Bias, P., Mueller, U., et al.[2018]

The biosimilar filgrastim (BK0023) demonstrated comparable biological activity, efficacy, and safety to the reference drug Neupogen® in both in vitro and in vivo studies, including a phase I trial with healthy volunteers.

BK0023 showed similar pharmacokinetic profiles to Neupogen®, indicating it could be a viable alternative for treating neutropenia in patients undergoing cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and clinical phase I studies of a new recombinant Filgrastim (BK0023) in comparison with Neupogen®. Crobu, D., Spinetti, G., Schrepfer, R., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pegfilgrastim; a neutrophil mediated granulocyte colony stimulating factor-expanding uses in cancer chemotherapy. [2022]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Effectiveness of Leukostim, a Russian preparation of granulocyte colony-stimulating factor, in the treatment of chemotherapy-induced neutropenia in patients with malignant tumors]. [2015]

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

Clinical Outcomes of Treatment with Filgrastim Versus a Filgrastim Biosimilar and Febrile Neutropenia-Associated Costs Among Patients with Nonmyeloid Cancer Undergoing Chemotherapy. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Mobilization of Hematopoietic Stem Cells into Peripheral Blood for Autologous Transplantation Seems Less Efficacious in Poor Mobilizers with the Use of a Biosimilar of Filgrastim and Plerixafor: A Retrospective Comparative Analysis. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A clinical comparison of the efficacy and safety of biosimilar G-CSF and originator G-CSF in haematopoietic stem cell mobilization. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Clinical safety of tbo-filgrastim, a short-acting human granulocyte colony-stimulating factor. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Preclinical and clinical phase I studies of a new recombinant Filgrastim (BK0023) in comparison with Neupogen®. [2021]

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

Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

How did the Introduction of Biosimilar Filgrastim Influence the Prescribing Pattern of Granulocyte Colony-Stimulating Factors? Results from a Multicentre, Population-Based Study, from Five Italian Centres in the Years 2009-2014. [2022]