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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the collection and safety of stem cells from healthy donors using filgrastim. Filgrastim moves stem cells from the bone marrow into the bloodstream, facilitating collection. The trial aims to ensure this process is safe for both donors and recipients of these stem cells in transplants. Individuals without autoimmune disorders, a history of blood clots, or pregnancy might qualify for this study. Donations are particularly sought from those willing to contribute to unrelated stem cell transplants. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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 prior data suggests that this method is safe for healthy donors?

Research has shown that filgrastim, a drug used to help collect stem cells, is safe for healthy donors. Used for over 30 years, it is generally well-tolerated. A 10-year study with 244 healthy donors found no new safety issues. Another study indicated that filgrastim is also safe for children when used to collect stem cells. Although information on long-term effects is limited, current evidence supports its safety for donors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Filgrastim-mobilized stem cells are unique because they offer a novel way to collect stem cells from healthy donors. Unlike traditional stem cell collection methods that require invasive bone marrow extraction, this approach uses filgrastim to safely stimulate the release of stem cells into the bloodstream, making the collection process less invasive and more comfortable for donors. Researchers are excited about this treatment because it could significantly increase the number of potential donors and streamline the donation process, ultimately enhancing the availability of stem cells for patients in need.

What evidence suggests that filgrastim-mobilized stem cells are effective for stem cell transplantation?

Research has shown that filgrastim aids in gathering essential stem cells for successful transplants. Both the original filgrastim and its similar versions perform equally well for this purpose. In healthy donors, filgrastim prompts stem cells to enter the bloodstream, facilitating easier collection without causing long-term health issues. Studies have found no increase in cancer or other diseases in donors compared to non-donors. Overall, current research indicates that collecting stem cells with filgrastim is both effective and safe. ^{3 6 7 8 9}

Who Is on the Research Team?

John P Miller, MD, PhD

Principal Investigator

National Marrow Donor Program

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11372396/

Long-term outcomes of peripheral blood stem cell ... PBSC and BM donors had no differences in incidence rates for myeloid, lymphoid, other cancers, autoimmune diseases, or thrombotic events.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9990321/

Comparison of Biosimilar Filgrastim with Innovator ... A total of 114 patients, including 97 cancer patients and 17 healthy donors, underwent successful CD34+ stem cell mobilization using G-CSF with chemotherapy (35 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473050225000473

Comparison of the efficacy and total cost of peripheral ... This retrospective study evaluated the efficacy and total cost of switching from filgrastim (Neupogen) to its biosimilar, filgrastim-aafi (Nivestym), ...

4. jhoponline.com jhoponline.com/issue-archive/2022-issues/june-2022-vol-12-no-3/comparing-single-center-outcomes-between-reference-and-biosimilar-granulocyte-colony-stimulating-factor-drugs-used-for-autologous-stem-cell-mobilization

Comparing Single-Center Outcomes Between Reference ... The use of a biosimilar G-CSF drug demonstrated mobilization outcomes similar to the reference drug in patients who had undergone ASCT.

5. astctjournal.org astctjournal.org/article/S1083-8791(17)31718-4/fulltext

Application of Peripheral Blood Stem Cell Collection in ... Regeneration, health status and quality of life after rhG-CSF-stimulated stem cell collection in healthy donors: a cross-sectional study. Bone Marrow ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11372387/

Donor safety confirmed - PMC ... filgrastim for stem cell mobilization is safe for volunteer hematopoietic stem cell donors. There was a period of >30 years in which bone ...

7. nature.com nature.com/articles/s41598-019-56477-w

Efficacy and Safety of Nivestim Versus Neupogen for ... Nivestim was found to be safe and non-inferior to Neupogen for chemo-mobilization of stem cells for autoSCT, and associated with lower cost and shorter length ...

8. centerforbiosimilars.com centerforbiosimilars.com/view/ten-years-of-data-support-safety-of-biosimilar-filgrastim-for-donor-mobilization

Ten Years of Data Support Safety of Biosimilar Filgrastim ... A 10-year prospective follow-up of 244 healthy stem cell donors found no new safety concerns with Sandoz's filgrastim biosimilar, reinforcing ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924002726

Long-term outcomes of peripheral blood stem cell ... There is a paucity of safety data regarding donors' long-term adverse events. This prospective, observational study combined PBSC donors ...