Mozobil for Neutropenia

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by David H McDermott, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

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

No Placebo Group

Approved in 2 Jurisdictions

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).

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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.

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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.

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, MD

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

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

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] On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil; Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval.

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] Plerixafor (Mozobil, AMD3100) with granulocyte-colony stimulating factor (G-CSF) mobilizes more CD34+ cells/kg compared to G-CSF alone. Given that plerixafor enhances mobilization of multiple white blood cell lineages, we determined if more storage space is required for products collected from patients mobilized with plerixafor.

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] To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma.

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] AMD3100 was originally discovered as an anti-HIV agent effective in inhibiting the replication of HIV in vitro at nanomolar concentrations. We found it to be a potent and selective antagonist of CXCR4, the receptor for the chemokine SDF-1 (now called CXCL12). AMD3100 was then developed, and marketed, as a stem cell mobilizer, and renamed plerixafor (Mozobil™). The path to the discovery of Mozobil™ as a stem cell mobilizer was described in Biochem. Pharmacol. 77: 1655-1664 (2009). Here I review the recent advances that have consolidated the role of plerixafor in mobilizing hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) from the bone marrow into the blood circulation. Plerixafor acts synergistically with granulocyte colony-stimulating factor (G-CSF), and its usefulness has been proven particularly for the mobilization of HSCs and HPCs for autologous stem cell transplantation in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM). Plerixafor also has great potential for the treatment of hematological malignancies other than NHL and MM, and non-hematological malignancies, and, eventually, several other diseases depending on the CXCL12-CXCR4 interaction. Various AMD3100 analogs have been described (i.e. AMD11070, AMD3465, KRH-3955, T-140, and 4F-benzoyl-TN14003), primarily as potential anti-HIV agents. They are all strong CXCR4 antagonists. Their role in stem cell mobilization remains to be assessed.

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] Plerixafor (Mozobil®) is a CXCR4 chemokine receptor antagonist that is indicated for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the peripheral blood for collection and subsequent autologous stem-cell transplantation in patients who have non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) [US] and in patients who have lymphoma or MM and are poor mobilizers (EU). This article reviews the clinical efficacy and tolerability of subcutaneous plerixafor for stem-cell mobilization in patients with lymphoma or MM, as well as summarizing its pharmacological properties. Pharmacoeconomic analyses of plerixafor and decision-making algorithms intended to optimize its use are also discussed. Plerixafor plus G-CSF mobilized stem cells more efficiently than placebo plus G-CSF in adults with NHL or MM, according to the results of two randomized, double-blind, multicentre trials. In these trials, significantly more plerixafor plus G-CSF recipients than placebo plus G-CSF recipients reached primary apheresis targets in significantly fewer apheresis days. In the trial in patients with NHL, significantly more plerixafor plus G-CSF than placebo plus G-CSF recipients proceeded to transplantation. Results of compassionate-use studies in patients with lymphoma or MM demonstrated that plerixafor plus G-CSF successfully mobilized stem cells in the majority of patients who were poor mobilizers (i.e. sufficient CD34+ cells had not been collected during apheresis or apheresis had not occurred because of low peripheral blood CD34+ cell counts). Results of compassionate-use studies and additional studies in patients with lymphoma or MM also demonstrated that plerixafor plus G-CSF successfully mobilized stem cells in predicted poor mobilizers, such as heavily pretreated patients considered to be at high risk of mobilization failure. In addition, a small study showed mobilization with pre-emptive plerixafor to be effective. Subcutaneous plerixafor was generally well tolerated during stem-cell mobilization in patients with NHL or MM; the most commonly occurring treatment-related adverse events in plerixafor plus G-CSF recipients included injection-site reactions and gastrointestinal adverse events. Preliminary results of a US cost-effectiveness analysis suggest that plerixafor plus G-CSF is a cost-saving option compared with cyclophosphamide plus G-CSF. A retrospective US cost analysis found no significant difference between plerixafor plus G-CSF and cyclophosphamide plus G-CSF recipients in the median total cost of initial mobilization, suggesting that the cost of plerixafor may be offset by increased utilization of other resources in patients receiving alternative mobilization regimens. Additional cost analyses examined the use of pre-emptive plerixafor; institutions have developed decision-making algorithms, mainly relating to the use of pre-emptive plerixafor, to help optimize its use. In conclusion, plerixafor is a valuable stem-cell mobilizer for use in combination with G-CSF in patients with lymphoma or MM, particularly in patients who are poor mobilizers or predicted poor mobilizers.

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

Mobilization of hematopoietic stem cells by plerixafor alone in children: a sequential Bayesian trial. [2021] The rapid kinetics of hematopoietic stem cells induced by Plerixafor (Mozobil®, Genzyme) should be of particular interest in children. We therefore conducted a prospective trial to determine whether a one-day mobilization by plerixafor alone was efficient enough in children with cancer.

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] In patients failing successful conventional mobilization of hematopoietic progenitor cells (HPC) plerixafor (Mozobil(®)) seems to be an alternative. We report a series of 14 patients with multiple myeloma or NHL successfully mobilized and harvested by plerixafor together with large-volume leukaphereses (LVL).