Filgrastim-Mobilized Stem Cell Collection for Healthy Donors

Recruiting at 19 trial locations

Overseen By Lisa Erickson

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Center for International Blood and Marrow Transplant Research

Must not be taking: Lithium, Experimental agents

Disqualifiers: Pregnancy, Autoimmune disorders, Thrombocytopenia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

60000 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to: * Establish and evaluate a system for collection of filgrastim-mobilized peripheral blood stem cells from National Marrow Donor Program donors (NMDP) donors * Assess the safety among NMDP donors of filgrastim administration and PBSC leukapheresis * Assess the safety and efficacy of filgrastim-mobilized PBSC in unrelated donor hematopoietic stem cell transplant recipients * Determine the acceptability of stem cell donation by filgrastim stimulated apheresis in normal donors

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking lithium.

What data supports the effectiveness of the drug Filgrastim-Mobilized Stem Cells for healthy donors?

Research shows that Filgrastim, also known as Neupogen, is effective in mobilizing stem cells in healthy donors. Studies comparing the original Filgrastim to its biosimilars, like Nivestim, have demonstrated similar effectiveness in stem cell mobilization. ^{1 2 3 4 5}

Is Filgrastim safe for healthy donors?

Filgrastim, also known as Neupogen and its biosimilars like Zarxio and Nivestim, has been widely used and studied for safety in humans, particularly for preventing infections and mobilizing stem cells. Studies show that both the original and biosimilar versions have a comparable safety profile, indicating they are generally safe for use in healthy donors. ^{1 2 4 5 6}

How is the drug Filgrastim-Mobilized Stem Cells different from other treatments?

Filgrastim-Mobilized Stem Cells are unique because they use a drug called filgrastim to stimulate the production and release of stem cells from the bone marrow into the bloodstream, which can then be collected for transplantation. This approach is different from other treatments as it specifically mobilizes stem cells, making it useful for stem cell collection in healthy donors. ^{1 2 3 4 6}

Research Team

John P Miller, MD, PhD

Principal Investigator

National Marrow Donor Program

Eligibility Criteria

This trial is for healthy individuals eligible to donate stem cells, similar to marrow donors. They must not be pregnant or breastfeeding without interruption, have no history of certain eye conditions (iritis/episcleritis), low platelet counts, sickle cell trait, lithium treatment, sensitivity to filgrastim or E. coli proteins, autoimmune disorders unless successfully treated thyroid disease, and no deep vein thrombosis or pulmonary embolism.

Inclusion Criteria

Confirmatory pregnancy test must be performed within 15 days of collection and prior to the start of filgrastim administration; this may require more than one test to be performed.

I meet the criteria for marrow donation as per the Donor Center Manual.

Exclusion Criteria

I am currently taking lithium.

I am allergic to filgrastim or similar medications.

I am not pregnant or can stop breastfeeding during treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Donor Education and Evaluation

Donors are identified, educated, and evaluated for participation in the stem cell donation process

2 weeks

Filgrastim Administration

Administration and monitoring of the stem cell mobilizing agent filgrastim to donors

5 days

Leukapheresis

Collection of peripheral blood stem cell products by leukapheresis

1 day

Follow-up

Long-term follow-up of donors to assess safety and efficacy of the donation process

Long-term

Treatment Details

Interventions

• Filgrastim-Mobilized Stem Cells

Trial Overview The study tests a system for collecting stem cells from unrelated donors using a drug called filgrastim. It looks at the safety of this drug and procedure in donors and how well these collected stem cells work in transplant recipients needing new blood-forming cells.

Filgrastim-Mobilized Stem Cells is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Neupogen for:

• Neutropenia
• Febrile neutropenia
• Mobilization of peripheral blood stem cells for transplantation

Approved in United States as Neupogen for:

• Neutropenia
• Febrile neutropenia
• Mobilization of peripheral blood stem cells for transplantation
• Acute myeloid leukemia

Approved in Canada as Neupogen for:

• Neutropenia
• Febrile neutropenia
• Mobilization of peripheral blood stem cells for transplantation

Approved in Japan as Neupogen for:

• Neutropenia
• Febrile neutropenia
• Mobilization of peripheral blood stem cells for transplantation

Who Is Running the Clinical Trial?

Center for International Blood and Marrow Transplant Research

Lead Sponsor

Trials

40

Recruited

200,190,000+

National Marrow Donor Program

Collaborator

Trials

63

Recruited

202,000+

Findings from Research

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 comparing the originator filgrastim (Neupogen) with three EU-approved biosimilars showed that all products maintained a high level of similarity in quality attributes, including protein content and impurity levels, up to 5 years post-approval.

The biological activity of the biosimilars was comparable to the reference standard, indicating that they are equally effective in treating neutropenia-related conditions in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical Comparison of the Originator Granulocyte-colony Stimulating Factor Filgrastim and its Biosimilars. Orlik, G., Khan, MA., Grieb, P.[2019]

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]

Biosimilar rhG-CSF (Zarzio) has been shown to be effective and well-tolerated in facilitating neutrophil and platelet engraftment in patients undergoing autologous stem cell transplantation (AHSCT), based on two studies involving 110 patients.

The biosimilar demonstrated comparable kinetics of peripheral blood stem cell (PBSC) mobilization and yield of CD34+ cells to the originator product, indicating its efficacy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral blood stem cell mobilization and engraftment after autologous stem cell transplantation with biosimilar rhG-CSF. Reményi, P., Gopcsa, L., Marton, I., et al.[2018]

In a study comparing the original filgrastim (Neupogen®) and its biosimilar (Nivestim®) for stem cell mobilization in healthy donors, both were found to be equally effective, requiring a similar median number of doses to achieve the target CD34+ cell count.

The study included 157 healthy donors (89 received Neupogen® and 68 received Nivestim®), suggesting that Nivestim® can be a viable alternative to Neupogen®; however, further larger randomized studies are needed to assess the safety and transplant outcomes associated with Nivestim®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the effectiveness of biosimilar filgrastim (Nivestim®) versus original filgrastim (Neupogen®) for stem cell mobilization in adult and pediatric healthy donors. Muffarrej, D., Hashem, H., Tbakhi, A., et al.[2023]

NMR spectroscopy can effectively assess the three-dimensional structure of filgrastim (Neupogen®), providing detailed insights into its conformation and stability, particularly under varying pH conditions.

The study found that polysorbate, a common excipient, does not significantly interact with filgrastim, allowing for accurate structural analysis, which is crucial for ensuring the quality and comparability of biosimilar versions of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring Effects of Excipients, Formulation Parameters and Mutations on the High Order Structure of Filgrastim by NMR. Aubin, Y., Hodgson, DJ., Thach, WB., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Analytical Comparison of the Originator Granulocyte-colony Stimulating Factor Filgrastim and its Biosimilars. [2019]

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

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

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

Peripheral blood stem cell mobilization and engraftment after autologous stem cell transplantation with biosimilar rhG-CSF. [2018]

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

Comparing the effectiveness of biosimilar filgrastim (Nivestim®) versus original filgrastim (Neupogen®) for stem cell mobilization in adult and pediatric healthy donors. [2023]

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

Monitoring Effects of Excipients, Formulation Parameters and Mutations on the High Order Structure of Filgrastim by NMR. [2018]