Filgrastim + Dexamethasone for Granulocyte Donation

Recruiting at 1 trial location

Overseen By Kamille A West-Mitchell, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: National Institutes of Health Clinical Center (CC)

Must be taking: Filgrastim, Dexamethasone

Must not be taking: Lithium

Disqualifiers: Coronary heart disease, Diabetes, 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

Compensation: Varies

Number of Visits: 13

Duration: 12 months

1000 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you have hypertension or peptic ulcer disease, these must be well-controlled with medications. If you are on lithium therapy, you cannot participate in the trial.

What data supports the effectiveness of the drug combination of Filgrastim and Dexamethasone for granulocyte donation?

Research shows that the combination of Filgrastim (a drug that helps the body make more white blood cells) and Dexamethasone (a steroid) is effective in increasing the number of granulocytes (a type of white blood cell) in donors. This combination is commonly used to help collect more granulocytes from donors, which can be important for patients needing these cells. ^{1 2 3 4 5}

Is Filgrastim generally safe for human use?

Filgrastim, a type of granulocyte colony-stimulating factor (G-CSF), is widely used to treat low white blood cell counts caused by chemotherapy, and studies have shown it to be safe with no reported adverse side effects in patients. It is considered a standard treatment for mobilizing stem cells for bone marrow transplants. ^{1 3 5 6 7}

How does the drug Filgrastim + Dexamethasone for Granulocyte Donation differ from other treatments?

Filgrastim is a drug that stimulates the production of white blood cells, and when combined with Dexamethasone, it may enhance the mobilization of granulocytes (a type of white blood cell) for donation. This combination is unique because it leverages the effects of both drugs to potentially improve the efficiency of granulocyte collection, which is not a standard treatment for any specific condition but rather a method to aid in granulocyte donation. ^{1 5 6 7 8}

What is the purpose of this trial?

Background: - White blood cells called granulocytes help the body fight infection. People who have had chemotherapy or bone marrow transplants may have very low numbers of these cells. Transfusions of these cells can help improve the body's ability to fight infection. However, most of the cells are located in the bone marrow or spleen, and are hard to collect from healthy donors. Two drugs, filgrastim and dexamethasone, can help move the cells to the bloodstream to be collected by apheresis. Researchers want to study the best ways to collect these white blood cells. They also want to monitor the effects of the injections and donations on the volunteer donors. Objectives: - To improve the amount and quality of granulocytes (white blood cells) collected by apheresis for donation. Eligibility: - Healthy volunteers between 18 and 75 years of age. Design: * Participants will be screened with a physical exam and medical history. Initial blood tests will be done to check for eligibility. * Participants will donate granulocytes by apheresis a maximum of 12 times in 1 year. Donations will not usually be requested more often than every 4 weeks. Donors will be allowed to decline participation at any time. * Participants will have one injection of filgrastim 12 to 24 hours before donation. They will also have two tablets of dexamethasone 12 hours before donation. * White blood cells will be collected through apheresis. The apheresis will last about 2 hours. * Participants will be eligible to donate until they reach their 76th birthday....

Research Team

Kamille A West-Mitchell, M.D.

Principal Investigator

National Institutes of Health Clinical Center (CC)

Eligibility Criteria

Healthy volunteers aged 18-75 can join this trial to improve white blood cell collection for donations. They must meet standard donor criteria, have well-controlled hypertension or peptic ulcer disease if present, and not be underweight or have a history of severe heart disease, uncontrolled high blood pressure, hepatitis, drug use, insulin-requiring diabetes, active ulcers, certain eye conditions (iritis/episcleritis), sickle cell disease (trait is okay), lithium therapy, pregnancy/nursing or poor kidney function.

Inclusion Criteria

I meet the requirements to donate blood as per the latest health standards.

My high blood pressure is under control with medication.

My past peptic ulcer symptoms are under control with medication.

Exclusion Criteria

Uncontrolled hypertension (systolic BP >160, diastolic BP >100)

Information obtained from health history screen that does not meet the allogeneic donor eligibility criteria of the AABB Standards or the FDA CFR

I have diabetes and need insulin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive injections of filgrastim and dexamethasone before donating granulocytes by apheresis

12 months

Up to 12 visits (in-person) per year

Follow-up

Participants are monitored for short-term and long-term adverse effects of G-CSF and dexamethasone

Annually

Treatment Details

Interventions

• Dexamethasone
• Filgrastim

Trial Overview The trial tests the effectiveness of filgrastim and dexamethasone in increasing the amount and quality of granulocytes collected from donors through apheresis. Participants will receive an injection of filgrastim and two tablets of dexamethasone before undergoing a roughly 2-hour apheresis procedure up to 12 times per year.

Participant Groups

Group I: Donors Experimental Treatment 2 Interventions

volunteer healthy donors willing to receive G-CSF and dexamethasone and undergo leukapheresis

Who Is Running the Clinical Trial?

National Institutes of Health Clinical Center (CC)

Lead Sponsor

Trials

391

Recruited

30,880,000+

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]

A study analyzing 1198 granulocyte collections from 137 donors over 13 years found that higher baseline absolute neutrophil counts (ANC) and platelet counts lead to better responses to G-CSF/dex stimulation, resulting in higher yields of granulocytes.

The research concluded that a fixed dose of 480 micrograms of G-CSF is as effective as weight-based dosing, suggesting that monitoring donor ANC after multiple donations could optimize granulocyte collection outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The determinants of granulocyte yield in 1198 granulocyte concentrates collected from unrelated volunteer donors mobilized with dexamethasone and granulocyte-colony-stimulating factor: a 13-year experience. Quillen, K., Yau, YY., Leitman, SF.[2021]

Filgrastim significantly reduces the incidence of febrile neutropenia and severe neutropenia in patients undergoing chemotherapy, with relative risks of 0.63 and 0.50, respectively, based on a systematic review of 25 studies involving 1194 articles.

The most common adverse effect reported with filgrastim treatment is bone pain, which has a relative risk of 2.61, indicating it is a notable side effect to consider when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. Dale, DC., Crawford, J., Klippel, Z., et al.[2022]

A study involving 92 granulocyte donors who received G-CSF three or more times showed no significant differences in blood counts or C-reactive protein levels compared to matched platelet donors, suggesting that G-CSF does not adversely affect blood health in the long term.

At a median follow-up of 10 years, the incidence of serious health events like malignancies and coronary artery disease was similar between granulocyte donors and platelet donors, indicating that the G-CSF/dexamethasone regimen appears to be safe for repeated use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten-year follow-up of unrelated volunteer granulocyte donors who have received multiple cycles of granulocyte-colony-stimulating factor and dexamethasone. Quillen, K., Byrne, P., Yau, YY., et al.[2021]

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]

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]

This study identified and quantified low-level product-related variants in filgrastim products, including newly discovered variants, using advanced mass spectrometry techniques.

Despite the presence of these variants in some filgrastim products, they are mostly found at levels below 1% and are not expected to have any significant clinical impact on their efficacy or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Low-Level Product-Related Variants in Filgrastim Products Presently Available in Highly Regulated Markets. Hausberger, A., Lamanna, WC., Hartinger, M., et al.[2017]

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

The determinants of granulocyte yield in 1198 granulocyte concentrates collected from unrelated volunteer donors mobilized with dexamethasone and granulocyte-colony-stimulating factor: a 13-year experience. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. [2022]

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

Ten-year follow-up of unrelated volunteer granulocyte donors who have received multiple cycles of granulocyte-colony-stimulating factor and dexamethasone. [2021]

5. England pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Identification of Low-Level Product-Related Variants in Filgrastim Products Presently Available in Highly Regulated Markets. [2017]