Mozobil for Neutropenia

Recruiting in Bethesda (>99 mi)

+1 other 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

Trial Summary

What is the purpose of this trial?

Background: * WHIMS (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome) is caused by various genetic changes that increase the activity of the chemokine receptor, CXCR4. Excessive function of this receptor causes mature neutrophils (part of the white blood cells) to be retained within the bone marrow rather than being released to the blood and is one of the causes of severe inherited neutropenia (low white blood counts). In neutropenia, the body is less able to fight off infection. Patients with WHIMS usually are at risk for skin, soft tissue, sinus, and lung infections, which can result in loss of hearing, teeth, and lung function. * Current treatment for WHIMS consists of regular injections of a white blood cell growth stimulating medication called granulocyte colony stimulating factor (G-CSF), and supplemental immunoglobulin (antibody). These therapies are expensive, nonspecific, have significant side effects and toxicities, and do not fully correct all problems, especially warts and cancers related to human papillomavirus (HPV). * A drug called Mozobil has been approved for use in combination with G-CSF to increase the number of stem cells that can be collected prior to bone marrow transplantation. Mozobil may offer a specific and well-tolerated new treatment for WHIMS and other syndromes characterized by neutropenia. Objectives: * To evaluate whether Mozobil is safe and effective to treat neutropenia (low white blood cell count) in patients with WHIMS. * To determine an appropriate treatment dose of Mozobil, within currently approved dosage levels. Eligibility: - Individuals between 18 and 75 years of age who have been diagnosed with WHIMS and have a history of severe infections. Design: * Potential participants will undergo a screening with a medical history, physical examination, questionnaire, heart and lung function scans, and blood and urine samples. Tests will also be done for hepatitis B and C virus, and human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS), as well as to check neutrophil function. * Patients who are being treated with G-CSF will stop injections for 2 days before being admitted to the National Institutes of Health (NIH) Clinical Center. * Patients may participate in a Dose Escalation study and receive increasing doses of Mozobil over 5 days of treatment until their white blood cell count improves sufficiently or the maximum approved dose is reached. Blood samples will be taken regularly throughout the treatment process. Patients will then receive an additional dose of Mozobil at the maximum approved dose or the dose sufficient to cause improvement, before restarting the G-CSF injections. * Patients may also participate in a long-term Chronic Dosing study and receive Mozobil once or twice a day for up to a maximum of 60 months.

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.

What data supports the effectiveness of the drug Mozobil (Plerixafor) for treating neutropenia?

Mozobil (Plerixafor) is effective in mobilizing stem cells for transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma, especially when combined with G-CSF (a growth factor that stimulates white blood cell production). While it is primarily used for stem cell mobilization, its ability to enhance white blood cell production suggests potential benefits for conditions like neutropenia (low white blood cell count). ^{1 2 3 4 5}

How is the drug Mozobil different from other treatments for neutropenia?

Mozobil (Plerixafor) is unique because it works by blocking the CXCR4 receptor, which helps move stem cells from the bone marrow into the bloodstream, making it easier to collect them for transplantation. This mechanism is different from other treatments that may not target this specific receptor or process. ^{1 2 4 6 7}

Research Team

David H McDermott, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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, 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]

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]

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]

References

1. Switzerland 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. [2021]

2. 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]

3. China 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]. [2023]

4. England 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. [2021]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Mobilization of hematopoietic stem cells by plerixafor alone in children: a sequential Bayesian trial. [2021]

7. Switzerland 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. [2021]