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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to collect certain white blood cells, called granulocytes, from healthy donors to help patients fight infections. The researchers will use the drugs filgrastim (a granulocyte colony-stimulating factor) and dexamethasone (a corticosteroid) to test how these medications can move granulocytes into the bloodstream for easier collection. They will also monitor how these drugs and the donation process affect the donors. Healthy individuals with controlled hypertension or a history of peptic ulcer disease might be good candidates for this trial. As a Phase 4 trial, this research focuses on understanding how the already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for filgrastim and dexamethasone?

Research shows that using filgrastim and dexamethasone to collect granulocytes, a type of white blood cell, is generally safe for healthy donors. In previous studies, these drugs effectively moved granulocytes from the bone marrow into the bloodstream, facilitating collection.

Reports indicate that donors tolerate this collection method well. One study found that a similar drug combination was safe for donors. Another study showed that transfusions using these collected cells safely treated patients with severe infections.

Overall, evidence suggests that using filgrastim and dexamethasone for collecting granulocytes usually does not cause serious side effects in healthy donors. However, as with any medical procedure, monitoring for possible reactions is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Filgrastim combined with dexamethasone is unique because it enhances granulocyte donation by mobilizing more white blood cells from healthy donors. Unlike standard treatments that might involve just filgrastim alone, adding dexamethasone boosts the body's ability to produce and release these cells into the bloodstream more effectively. Researchers are excited about this combination because it could lead to more efficient and quicker collection of granulocytes, which are crucial for patients needing immune support, such as those undergoing chemotherapy.

What evidence suggests that filgrastim and dexamethasone might be effective for granulocyte donation?

Research has shown that using filgrastim and dexamethasone together increases the number of white blood cells called granulocytes in the bloodstream. In this trial, healthy volunteer donors will receive this combination to facilitate granulocyte donation. Studies have found that this drug combination moves these cells from the bone marrow (the soft tissue inside bones) into the bloodstream, making them easier to collect. A large review of granulocyte donations found this combination successful in mobilizing these important infection-fighting cells. Previous research confirms that these medications improve the amount and quality of granulocytes collected for transfusion, making it a useful method for preparing them for donation. ^{6 7 8 9 10}

Who Is on the Research Team?

Kamille A West-Mitchell, M.D.

Principal Investigator

National Institutes of Health Clinical Center (CC)

Are You a Good Fit for This Trial?

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

Pregnancy or nursing (breastfeeding)

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39601217/

Factors influencing white blood cell mobilisation in healthy ... A retrospective analysis was conducted on mobilisation data from 312 granulocyte collections from healthy donors between January 2020 and May 2023.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3421027/

The determinants of granulocyte yield in 1198 ... The combination of granulocyte–colony-stimulating factor (G-CSF [filgrastim]) and dexamethasone (G-CSF/dex) is an effective granulocyte mobilization regimen, ...

3. aetna.com aetna.com/cpb/medical/data/1_99/0055.html

Hematopoietic Colony-Stimulating Factors (CSFs) The effectiveness of tbo-filgrastim was determined based on study results that showed that patients receiving tbo-filgrastim recovered from severe ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2008.01997.x

The determinants of granulocyte yield in 1198 ... The outcome variables include the preprocedure absolute neutrophil count (preANC), which reflects G-CSF/dex stimulation, and the granulocyte ...

5. hhs.texas.gov hhs.texas.gov/sites/default/files/documents/apr-2023-durb-agenda-item4c.pdf

Colony Stimulating Factors Therapeutic Class Review (TCR) Labeling for filgrastim, filgrastim-aafi, filgrastim-ayow, and filgrastim-sndz report a shift towards earlier granulocyte progenitor cells ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3776445/

Efficacy and Side Effects of Granulocyte Collection in ... Granulocyte mobilization with lenograstim with or without dexamethasone was a safe and effective regimen for granulocyte mobilization. Side effects were ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473050224000454

Granulocyte transfusions in life-threatening infections of ... Granulocyte transfusions appear to be safe and effective supportive treatment in neutropenic children with hematologic/oncologic diseases and severe infections.

8. astctjournal.org astctjournal.org/article/S1083-8791(17)30625-0/fulltext

Granulocyte Transfusions: A Critical Reappraisal Granulocyte transfusions are used as a life-saving therapy for neutropenic patients with severe infections.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3424604/

Ten-year follow-up of unrelated volunteer granulocyte ... ... G-CSF is prudent, our data suggest that G-CSF/dexamethasone stimulation appears to be safe. Before the mid-1990s, granulocyte transfusion therapy was ...

10. haematologica.org haematologica.org/article/view/4914

Granulocyte concentrates: prolonged functional capacity ... Granulocyte concentrates collected by leukapheresis are usually transfused as quickly as possible, preferably within 6 hours. Longer storage ...