Mozobil for Neutropenia

Recruiting at 1 trial location

Overseen By Elena J Cho

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

Disqualifiers: No WHIMS, Cardiac arrhythmia, Renal failure, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for people with WHIMS, a condition that impairs the body's ability to fight infections due to low white blood cell counts. The researchers aim to determine if Mozobil (also known as Plerixafor), a drug already used to boost stem cells, can safely and effectively treat low white blood cell counts in WHIMS patients. Participants will receive Mozobil, and their white blood cell levels will be monitored to find a suitable dose. This trial may suit adults diagnosed with WHIMS who frequently experience severe infections. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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

You will need to stop taking G-CSF injections for at least 2 days before and during the study.

Is there any evidence suggesting that Mozobil is likely to be safe for humans?

Research has shown that Mozobil, also known as Plerixafor, is generally safe. In earlier studies, most participants experienced no side effects. Although a few serious side effects occurred, they were rare and affected only a small number of people. Mozobil is already approved for increasing stem cells before bone marrow transplants, indicating its safety for certain uses. This information offers some reassurance about its safety for treating conditions like neutropenia (a low white blood cell count), though individual reactions may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for neutropenia, such as G-CSF injections that stimulate white blood cell production, Mozobil works by mobilizing stem cells from the bone marrow into the bloodstream. This unique mechanism can potentially enhance the body's ability to combat infections more effectively. Researchers are excited about Mozobil because it may provide a faster response compared to traditional treatments, offering quicker relief for patients with low white blood cell counts.

What evidence suggests that Mozobil might be an effective treatment for neutropenia?

Research has shown that Mozobil, also known as plerixafor, holds promise for treating neutropenia, a condition characterized by low levels of white blood cells. Studies have found that Mozobil increases the number of neutrophils (a type of white blood cell) in the bloodstream. It achieves this by blocking a receptor that typically retains these cells in the bone marrow, allowing more neutrophils to enter the bloodstream and combat infections. In early trials, patients who took long-term, low doses of Mozobil tolerated it well, with no major side effects. Overall, Mozobil has the potential to safely and effectively increase white blood cell counts in patients with conditions like WHIMS, reducing the risk of infections. ^{6 7 8 9 10}

Who Is on the Research Team?

David H McDermott, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Adults aged 18-75 with WHIMS, a condition causing low white blood cells and severe infections. Participants must not be pregnant or breastfeeding, agree to use two forms of contraception, stop certain medications before the study, have a personal physician, and provide samples for research.

Inclusion Criteria

Must not be pregnant or breastfeeding

Must have a personal physician

My male partner has had a vasectomy confirmed to prevent sperm production.

Exclusion Criteria

You have a condition called neutropenia, where your body doesn't produce enough infection-fighting cells, and the doctor doesn't think this medication will help you.

I have a serious heart rhythm problem or defect.

My kidneys are failing, needing dialysis or my creatinine clearance is below 15 mL/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Participants receive increasing doses of Mozobil over 5 days until white blood cell count improves or maximum dose is reached

1 week

Daily visits (in-person)

Chronic Dosing

Participants receive Mozobil once or twice a day for up to 60 months

60 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Mozobil

Trial Overview The trial is testing Mozobil's safety and effectiveness in treating neutropenia in WHIMS patients. It includes a Dose Escalation study to find the right dose over 5 days and a Chronic Dosing study for long-term treatment up to 60 months.

How Is the Trial Designed?

Group I: Treatment Arm Active Control 1 Intervention

neutropenia and infections

Mozobil is already approved in United States, European Union for the following indications:

Approved in United States as Mozobil for:

• Hematopoietic stem cell mobilization in patients with non-Hodgkin's lymphoma or multiple myeloma

Approved in European Union as Mozobil for:

• Hematopoietic stem cell mobilization in patients with lymphoma or multiple myeloma

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 phase-IIA study involving 5 children with solid malignancies, a single injection of 240 μg/kg plerixafor mobilized hematopoietic stem cells effectively, with peak CD34+ cell counts reached within 4 to 6 hours and no side effects observed.

Despite all patients meeting the threshold for apheresis, none achieved the target of collecting at least 5 × 10^6 CD34+/kg, indicating that while the mobilization was rapid, further optimization of the plerixafor regimen is needed for effective stem cell collection in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mobilization of hematopoietic stem cells by plerixafor alone in children: a sequential Bayesian trial. Chambon, F., Merlin, E., Rochette, E., et al.[2021]

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 study of 14 patients with multiple myeloma or non-Hodgkin lymphoma, the addition of plerixafor to G-CSF mobilization significantly increased the number of leukocytes and CD34+ cells in the blood, enhancing the effectiveness of stem cell harvesting.

Patients who received plerixafor during chemotherapy and G-CSF mobilization had a higher yield of CD34+ cells for transplantation compared to those mobilized with G-CSF alone, demonstrating that plerixafor can improve stem cell collection outcomes even in challenging mobilization scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful mobilization, intra-apheresis recruitment, and harvest of hematopoietic progenitor cells by addition of plerixafor and subsequent large-volume leukapheresis. Humpe, A., Buwitt-Beckmann, U., Schub, N., et al.[2021]

Plerixafor, when used with G-CSF, significantly improves stem cell mobilization in patients with non-Hodgkin's lymphoma or multiple myeloma, allowing more patients to reach transplantation targets in fewer apheresis days, as shown in two randomized trials.

The treatment is generally well tolerated, with common side effects being mild injection-site reactions and gastrointestinal issues, making it a safe option for patients, especially those who are poor mobilizers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plerixafor: a review of its use in stem-cell mobilization in patients with lymphoma or multiple myeloma. Keating, GM.[2021]

Plerixafor (Mozobil™) is a potent antagonist of the CXCR4 receptor and has been effectively used to mobilize hematopoietic stem cells (HSCs) and progenitor cells (HPCs) from bone marrow into the bloodstream, particularly for patients undergoing autologous stem cell transplantation for non-Hodgkin's lymphoma and multiple myeloma.

The drug works synergistically with granulocyte colony-stimulating factor (G-CSF) and shows promise for treating various hematological and non-hematological malignancies, highlighting its potential beyond just stem cell mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances on the use of the CXCR4 antagonist plerixafor (AMD3100, Mozobil™) and potential of other CXCR4 antagonists as stem cell mobilizers. De Clercq, E.[2021]

Plerixafor, approved by the FDA for use with G-CSF, significantly improves the mobilization of hematopoietic stem cells (HSC) for patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), with 59% of NHL patients and 72% of MM patients achieving the required cell collection in fewer apheresis sessions compared to placebo.

The treatment is generally safe, with common side effects including diarrhea, nausea, and fatigue, but the benefits in stem cell collection efficiency make it a valuable option for patients undergoing autologous transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA review summary: Mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. Brave, M., Farrell, A., Ching Lin, S., et al.[2021]

Plerixafor combined with G-CSF is an effective and safe method for mobilizing hematopoietic stem cells in lymphoma patients, achieving an overall acquisition success rate of 58.1% across different mobilization strategies.

The study identified that having fewer than 5 CD34+ cells/μl in peripheral blood before collection is a significant risk factor for poor stem cell collection, highlighting its importance as a predictive measure for successful mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Plerixafor Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Lymphoma Patients]. Guan, FS., He, DH., Li, Y., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4461468/

The CXCR4 antagonist AMD3100 redistributes leukocytes ... AMD3100 redistributes lymphocytes, monocytes and neutrophils from primary immune organs to secondary immune organs, peripheral tissues and blood.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3804935/

Neutrophil mobilization via plerixafor-mediated CXCR4 ... The CXCR4 antagonist plerixafor augments frequency of circulating neutrophils via release from the lung and prevents neutrophil homing to the bone marrow.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473050223002136

Plerixafor in autologous stem cell transplantation In the chemo-mobilized patient subgroup, plerixafor-mobilized patients experienced more febrile neutropenia attacks (p = 0.04). ... neutrophil and platelet ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/2040206619829382

Mozobil® (Plerixafor, AMD3100), 10 years after its ... AMD3100 efficiently depleted ASCs, including LLPCs. Combination with the proteasome inhibitor bortezomib significantly enhanced the depletion ...

5. ashpublications.org ashpublications.org/blood/article/123/15/2308/32255/A-phase-1-clinical-trial-of-long-term-low-dose

A phase 1 clinical trial of long-term, low-dose treatment of ... No drug-associated side effects were observed. These results provide preliminary evidence for the safety and clinical efficacy of long-term, low-dose plerixafor ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37561579/

A phase III randomized crossover trial of plerixafor versus G ... CONCLUSIONPlerixafor was not superior to G-CSF in patients with WHIM for TISS, the primary endpoint. Together with wart regression and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10541188/

A phase III randomized crossover trial of plerixafor versus G ... Safety outcomes. Seven serious adverse events (SAEs) occurred among 6 patients, 1 during the open-label G-CSF posttreatment phase and 6 during a treatment ...

8. aetna.com aetna.com/cpb/medical/data/700_799/0779.html

Plerixafor - Medical Clinical Policy Bulletins No side effects were observed. The authors stated that plerixafor may be an effective and safe agent for stem cell collection in pediatric patients with solid ...

9. medrxiv.org medrxiv.org/content/10.1101/2025.04.19.25325865v1.full.pdf

Continuous Infusion of the CXCR4 Antagonist Plerixafor for ... Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry. Orphanet J Rare Dis.

10. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT00903968?term=Plerixafor&rank=4

Combination Plerixafor (AMD3100)and Bortezomib in ... The purpose of this research study is to determine the safety of plerixafor and bortezomib, and the highest dose that can be given to people safely.