Stem Cell Mobilization for T Cell Lymphocytopenia

Recruiting at 1 trial location

Overseen By Irini Sereti, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Lithium, Anticoagulants, Immunomodulators, others

Disqualifiers: Autoimmune conditions, Leukemia, Hepatitis, 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: 7

Duration: 1 week

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome defined by consistently low CD4 T cell counts (\<300/mm3) without evidence of HIV infection or other known immunodeficiency. Patients with ICL are at risk for opportunistic infections typically associated with HIV/AIDS such as disseminated cryptococcal infection and severe human papillomavirus-related dysplasia. More than 20 years since the description of ICL, its etiology, pathogenesis, and management remain unclear. In this study we propose to administer the combination of granulocyte colony stimulating factor (G-CSF) and plerixafor to ICL patients and healthy volunteers with the objective of harvesting mobilized CD34+ hematopoietic progenitor cells (HPCs) by apheresis for transfer into immunocompromised mice and for study with in vitro assays. The mice studies would serve to investigate thymic development, survival, and trafficking of the mobilized human cells within murine lymphoid and non-lymphoid organs. HPCs are used for various therapies and there is an increasing use of agents that stimulate the bone marrow to produce progenitor cells and move them into the bloodstream where they may be harvested by apheresis. Not all patients respond to GCSF with vigorous HPC mobilization. The binding of chemokine receptor CXCR4 to stromal cell derived factor (SDF-1 or CXCL12) is an important interaction between a hematopoietic progenitor cell and its marrow environment. Plerixafor is a CXCR4 inhibitor which blocks binding to SDF-1 resulting in the release of hematopoietic progenitor cells (CD34+) into peripheral circulation. In pharmacodynamic studies of plerixafor in conjunction with G-CSF compared to G-CSF and placebo, a two-fold increase in CD34+ cell count was observed. Due to the important role CXCR4 plays in immune cell trafficking and its potential role in the pathogenesis of ICL, we propose as a secondary objective to assess peripheral CD4 T cell and CD34+ hematopoietic progenitor cell numbers and functions in ICL patients compared to controls following G-CSF and plerixafor administration. Study participants will be screened within 12 weeks prior to the study period. Eligible participants will receive G-CSF for 5 days with hospitalization on Day 4 for plerixafor injection followed by apheresis on Day 5. Participants will return for examinations and blood draws on Days 8 and 12.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving lithium or have used systemic immune-modulatory agents in the past 6 months. It's best to discuss your specific medications with the trial team.

What safety data is available for stem cell mobilization treatments like Filgrastim and its biosimilars?

Safety data for Filgrastim and its biosimilars, such as Neupogen, Zarxio, and Nivestym, primarily comes from their use in treating chemotherapy-induced neutropenia. A retrospective study from 1991 to 2018 identified 11,183 adverse drug reaction reports, with common side effects including pyrexia, myalgia, back pain, arthralgia, and bone pain. Differences in adverse events and efficacy were noted between the originator and biosimilars. Large epidemiologic studies are recommended to confirm these findings. Filgrastim and its biosimilars have been approved in the US and Europe, with Zarxio being the first biosimilar approved in the US in 2015. ^{1 2 3 4 5}

Is the drug Filgrastim, Plerixafor a promising treatment for T Cell Lymphocytopenia?

Yes, Filgrastim and Plerixafor are promising because they help mobilize stem cells effectively, which is important for treatments like stem cell transplants. Studies show that these drugs work well together to collect the necessary stem cells, making them a valuable option for patients needing this type of therapy. ^{6 7 8 9 10}

What data supports the idea that Stem Cell Mobilization for T Cell Lymphocytopenia is an effective treatment?

The available research shows that drugs like filgrastim, which are used for stem cell mobilization, are effective in other conditions such as multiple myeloma. Studies have compared different versions of filgrastim and found them effective in mobilizing stem cells, which is a key part of the treatment process. Although the research does not directly address T Cell Lymphocytopenia, the success in similar conditions suggests potential effectiveness. ^{6 7 8 11 12}

Who Is on the Research Team?

Irini Sereti, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with a rare condition called Idiopathic CD4 Lymphocytopenia (ICL), which involves very low levels of certain immune cells. Participants must have documented ICL, be HIV negative, and not currently have any serious illnesses or conditions that could interfere with the study. They should also agree to use effective birth control during the study.

Inclusion Criteria

ICL patients with documented history of idiopathic CD4 lymphocytopenia

Willingness to have blood samples stored for future research

Established primary care provider

Exclusion Criteria

I need blood thinners other than aspirin or clopidogrel.

Hepatitis B and C seropositivity

Thrombocytopenia (platelets <100,000 cells/microL)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

12 weeks

Treatment

Participants receive G-CSF for 5 days with hospitalization on Day 4 for plerixafor injection followed by apheresis on Day 5

1 week

Daily visits for 5 days, including hospitalization on Day 4

Follow-up

Participants return for examinations and blood draws to monitor safety and effectiveness

1 week

2 visits (in-person) on Days 8 and 12

What Are the Treatments Tested in This Trial?

Interventions

• Filgrastim
• Plerixafor

Trial Overview The trial tests Plerixafor and Filgrastim's ability to mobilize stem cells in patients with ICL compared to healthy volunteers. These drugs may help move important progenitor cells into the bloodstream for collection and research on T cell development within mice models.

How Is the Trial Designed?

Group I: Plerixafor Experimental Treatment 1 Intervention

ICL and healthy volunteers will be given 0.24 mg/kg as a single dose (maximum dose: 40 mg) 11 hours prior to apheresis

Group II: Filgrastim Experimental Treatment 1 Intervention

ICL and healthy volunteers will be given 10 microgram/kg daily for 5 days administered according to a vial-based algorithm to reduce wastage and increase the G-CSF dose given to lighter-weight donors to improve CD34+ yields

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

Approved in United States as Neupogen for:

• Neutropenia
• Acute Myeloid Leukemia
• Bone Marrow Transplantation
• Chronic Neutropenia
• Leukemia
• Myelodysplastic Syndromes

Approved in European Union as Neupogen for:

• Neutropenia
• Acute Myeloid Leukemia
• Bone Marrow Transplantation
• Chronic Neutropenia
• Leukemia
• Myelodysplastic Syndromes

Approved in Canada as Neupogen for:

• Neutropenia
• Acute Myeloid Leukemia
• Bone Marrow Transplantation
• Chronic Neutropenia
• Leukemia
• Myelodysplastic Syndromes

Approved in Japan as Neupogen for:

• Neutropenia
• Acute Myeloid Leukemia
• Bone Marrow Transplantation
• Chronic Neutropenia
• Leukemia
• Myelodysplastic Syndromes

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study of 250 multiple myeloma patients, the mobilization efficiency of the G-CSF variants filgrastim, lenograstim, and the biosimilar Filgrastim Hexal was found to be similar, with all but one patient reaching the target of at least 2×10^6 CD34+ cells/kg body weight.

No significant differences in CD34+ cell mobilization and collection yields were observed among the three G-CSF variants, indicating that the biosimilar Filgrastim Hexal is as effective as the originator drugs for peripheral blood stem cell mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of biosimilar filgrastim, originator filgrastim, and lenograstim for autologous stem cell mobilization in patients with multiple myeloma. Lisenko, K., Baertsch, MA., Meiser, R., et al.[2018]

A study involving 40 patients with multiple myeloma showed that the biosimilar filgrastim is as effective as the originator G-CSF in mobilizing peripheral blood stem cells, with no significant differences in the number of CD34+ cells collected.

Both biosimilar and originator G-CSF groups had similar rates of mobilization failure (2.5% vs. 2.7%) and comparable outcomes in hematopoietic recovery and transplant-related toxicities, indicating the biosimilar's safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of biosimilar granulocyte colony-stimulating factor versus originator granulocyte colony-stimulating factor in peripheral blood stem cell mobilization in de novo multiple myeloma patients. Martino, M., Recchia, AG., Moscato, T., et al.[2018]

In a study of 243 donors for allogeneic hematopoietic stem cell transplantation, biosimilar filgrastim (Leucostim®) was found to be equally effective as original filgrastim (Neupogen®) and Lenograstim (Granocyte®) in mobilizing CD34(+) cells, which are crucial for stem cell transplants.

The median number of collected CD34(+) cells was similar across all three G-CSF agents, indicating that the choice of agent does not significantly impact the effectiveness of stem cell mobilization in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors. Sivgin, S., Karakus, E., Keklik, M., et al.[2018]

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]

In a Phase I clinical trial involving 56 healthy subjects, the recombinant filgrastim product Leucostim® demonstrated comparable pharmacokinetic and pharmacodynamic profiles to the reference product Neupogen®, indicating its potential as a biosimilar treatment for neutropenia.

Both products showed similar safety profiles, with no serious adverse events reported, reinforcing the safety of using Leucostim® as an alternative to Neupogen®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of biosimilar filgrastim with a reference product: pharmacokinetics, pharmacodynamics, and safety profiles in healthy volunteers. Choi, C., Yoo, BW., Kim, CO., et al.[2022]

A retrospective study of adverse drug reactions from 1991 to 2018 found that filgrastim biosimilars, such as Grasin® and Zarzio®, reported higher rates of specific side effects compared to the originator Neupogen®, indicating potential differences in safety profiles.

The study revealed that some biosimilars, like Zarzio® and Tevagrastim®, had significant reports of drug ineffectiveness, suggesting that their efficacy may not match that of the original filgrastim, highlighting the need for further large-scale studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. Rastogi, S., Shukla, S., Sharma, AK., et al.[2020]

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]

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-sndz (Zarxio) became the first biosimilar approved by the FDA in the US on March 6, 2015, for all indications of its reference product, Amgen's Neupogen.

This biosimilar is primarily used to treat neutropenia in cancer patients undergoing chemotherapy, demonstrating its efficacy in managing a common side effect of cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Totality of the evidence at work: The first U.S. biosimilar. Holzmann, J., Balser, S., Windisch, J.[2022]

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]

Plerixafor combined with G-CSF mobilizes a greater total number of nucleated and mononuclear cells compared to G-CSF alone, but results in a smaller proportion of CD34+ cells, which are crucial for stem cell transplants.

Patients mobilized with plerixafor required significantly more storage bags for their stem cell products (15 bags) compared to those mobilized with G-CSF alone (9 bags), potentially leading to logistical challenges and increased storage costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plerixafor mobilization leads to a lower ratio of CD34+ cells to total nucleated cells which results in greater storage costs. Tanhehco, YC., Adamski, J., Sell, M., et al.[2021]

In a prospective randomized trial involving 97 patients with multiple myeloma and non-Hodgkin lymphoma, tbo-filgrastim was found to be not inferior to filgrastim in terms of stem cell mobilization efficacy, with a mean collection of 11.6 CD34+ cells/kg compared to 10.0 CD34+ cells/kg for filgrastim.

Both tbo-filgrastim and filgrastim showed similar safety profiles, indicating that tbo-filgrastim can be a safe and effective alternative to filgrastim for stem cell mobilization in patients undergoing autologous hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Prospective Randomized, Open-Label, Noninferiority Study of Tbo-Filgrastim (Granix) versus Filgrastim (Neupogen) in Combination with Plerixafor for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma and Non-Hodgkin Lymphoma. Bhamidipati, PK., Fiala, MA., Grossman, BJ., et al.[2021]

Citations

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

Comparison of biosimilar filgrastim, originator filgrastim, and lenograstim for autologous stem cell mobilization in patients with multiple myeloma. [2018]

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

Efficacy of biosimilar granulocyte colony-stimulating factor versus originator granulocyte colony-stimulating factor in peripheral blood stem cell mobilization in de novo multiple myeloma patients. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

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

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

Comparison of biosimilar filgrastim with a reference product: pharmacokinetics, pharmacodynamics, and safety profiles in healthy volunteers. [2022]

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

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. [2020]

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

Totality of the evidence at work: The first U.S. biosimilar. [2022]

10. 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]

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

Plerixafor mobilization leads to a lower ratio of CD34+ cells to total nucleated cells which results in greater storage costs. [2021]

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

Results of a Prospective Randomized, Open-Label, Noninferiority Study of Tbo-Filgrastim (Granix) versus Filgrastim (Neupogen) in Combination with Plerixafor for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma and Non-Hodgkin Lymphoma. [2021]