Mavorixafor for Neutropenia

Recruiting at 111 trial locations

Overseen By Patient Affairs and Advocacy

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: X4 Pharmaceuticals

Must be taking: G-CSF

Must not be taking: Clozapine, Antiretrovirals, Antibiotics, others

Disqualifiers: Secondary neutropenia, Aplastic anemia, WHIM syndrome, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

176 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests mavorixafor, a drug that may benefit individuals with certain types of chronic neutropenia, a condition characterized by too few white blood cells and frequent serious infections. The trial aims to determine if mavorixafor can increase white blood cell counts and reduce infections. Participants will take either mavorixafor or a placebo (a pill with no active drug) daily for a year. Individuals with a chronic neutropenia disorder for at least six months and two or more serious infections in the past year may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that participants who are on G-CSF or other active background therapy must continue these medications at a stable dose and schedule throughout the study. If you are on other medications, the protocol does not specify whether you need to stop them.

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

Research has shown that mavorixafor is generally safe and well-tolerated. One study found that taking mavorixafor daily by mouth improved blood cell counts without causing any new or more severe side effects than those already known. Another study discovered that over four months, participants taking mavorixafor did not experience infections, even when they changed their other medications. These findings suggest that mavorixafor is safe for individuals with chronic neutropenia, a condition characterized by low levels of certain white blood cells. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Mavorixafor is unique because it targets neutropenia by acting on the CXCR4 receptor, which plays a crucial role in the movement and retention of neutrophils in the bone marrow. Most current treatments for neutropenia, like granulocyte colony-stimulating factors (G-CSFs), work by stimulating the production of neutrophils. In contrast, Mavorixafor helps mobilize these cells, potentially offering a new way to manage neutropenia. This novel mechanism of action excites researchers as it could provide an alternative for patients who do not respond well to existing therapies.

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

Research has shown that mavorixafor, an oral medication, can significantly increase the number of neutrophils in the blood. Neutrophils, a type of white blood cell, help the body fight infections. In this trial, participants will receive either mavorixafor or a placebo, a pill without active medicine, to compare their effects. One study found that people taking mavorixafor had more neutrophils and another type of white blood cell, lymphocytes, compared to those taking a placebo. Another study found that mavorixafor could maintain these higher neutrophil levels for more than 15 hours. This suggests that mavorixafor might benefit people with chronic neutropenia, a condition characterized by low neutrophil counts, by reducing the risk of infections. ^{2 3 6 7 8}

Who Is on the Research Team?

Vice President Global Head of Clinical Development and Safety

Principal Investigator

X4 Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for people with low white blood cell counts due to congenital or acquired neutropenic disorders, who have been on stable doses of standard treatments like G-CSF for at least a year. They must have had the disorder for over six months and show a specific low level of neutrophils without current infections.

Inclusion Criteria

Participants must maintain their G-CSF doses/regimens unchanged (unless for safety reasons) during the trial.

I have been on a stable dose of G-CSF or similar treatments for at least 4 weeks.

I have been diagnosed with a chronic neutropenic disorder not caused by medications, infections, or cancer for over 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mavorixafor or placebo orally once daily from Day 1 through Week 52

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mavorixafor

Trial Overview The study tests Mavorixafor's effectiveness in increasing white blood cells and reducing infection risks compared to a placebo. Participants will be randomly assigned to receive either Mavorixafor or an inactive substance while keeping their current treatment constant.

How Is the Trial Designed?

Group I: Mavorixafor Experimental Treatment 1 Intervention

Participants will receive mavorixafor orally once daily starting from Day 1 through Week 52.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo to match mavorixafor orally once daily starting from Day 1 through Week 52.

Who Is Running the Clinical Trial?

X4 Pharmaceuticals

Lead Sponsor

Trials

11

Recruited

400+

Published Research Related to This Trial

Mavorixafor, an oral CXCR4 antagonist, was well tolerated in a phase 2 study involving 8 adult patients with WHIM syndrome, showing no serious treatment-related adverse events.

The treatment led to significant increases in white blood cell counts and a reduction in yearly infection rates from 4.63 to 2.27 events, along with a 75% decrease in cutaneous warts, indicating its potential efficacy in managing WHIM syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome. Dale, DC., Firkin, F., Bolyard, AA., et al.[2021]

In a study involving 9 patients with metastatic clear cell renal cell carcinoma (ccRCC) who were unresponsive to nivolumab, the combination of mavorixafor and nivolumab showed potential antitumor activity, with one patient achieving a partial response and others experiencing stable disease for a median duration of 6.7 months.

Mavorixafor, an allosteric CXCR4 inhibitor, appears to enhance immune responses by increasing the infiltration of activated cytotoxic T cells and correlating with elevated levels of CXCL9, suggesting its mechanism may improve treatment outcomes when combined with PD-1 blockade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b trial of the CXCR4 inhibitor mavorixafor and nivolumab in advanced renal cell carcinoma patients with no prior response to nivolumab monotherapy. Choueiri, TK., Atkins, MB., Rose, TL., et al.[2022]

In men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel, the occurrence of grade ≥3 neutropenia was linked to improved overall survival (OS) and progression-free survival (PFS), suggesting that this side effect may indicate a more effective treatment response.

Patients with a low baseline neutrophil-lymphocyte ratio (NLR) were more likely to experience grade ≥3 neutropenia and had the longest OS, while those with a high NLR and no neutropenia had poorer outcomes, indicating that NLR could be a useful biomarker for predicting treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe neutropenia during cabazitaxel treatment is associated with survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of the TROPIC phase III trial. Meisel, A., von Felten, S., Vogt, DR., et al.[2022]

Mavorixafor, an oral CXCR4 inhibitor, significantly increased immune cell infiltration and activation in melanoma tumors, enhancing key immune signatures after 3 weeks of treatment.

The combination of mavorixafor with pembrolizumab further boosted immune responses, while maintaining an acceptable safety profile with mostly mild adverse events, suggesting its potential as a treatment for patients not responding to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavorixafor, an Orally Bioavailable CXCR4 Antagonist, Increases Immune Cell Infiltration and Inflammatory Status of Tumor Microenvironment in Patients with Melanoma. Andtbacka, RHI., Wang, Y., Pierce, RH., et al.[2023]

In a multicenter clinical trial involving 57 cancer patients, leucomax (rhGM-CSF) was found to significantly increase white blood cell and neutrophil counts, effectively reducing the incidence and duration of chemotherapy-induced leucopenia and neutropenia.

Leucomax was generally well-tolerated, with mild to moderate side effects, making it a valuable addition to cancer chemotherapy regimens to ensure timely treatment without delays due to low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Randomized controlled study of leucomax (recombinant human granulocyte-macrophage colony stimulating factor, rhGM-CSF) in the treatment of cancer chemotherapy-induced leucopenia]. Feng, F., Zhou, L.[2006]

In a study of 80 metastatic castration-resistant prostate cancer patients treated with first-line docetaxel, those who experienced severe neutropenia (Grade 4) had significantly better overall survival (39.3 months) compared to those with no or mild neutropenia (11.6 months).

The results suggest that docetaxel-induced neutropenia may be a marker of better treatment response and survival outcomes, indicating that patients with severe neutropenia could have a more favorable prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy-Induced Neutropenia and Outcome in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With First-Line Docetaxel. Buttigliero, C., Tucci, M., Vignani, F., et al.[2019]

In a study involving women undergoing four cycles of chemotherapy, pegfilgrastim demonstrated a comparable safety profile to filgrastim while providing effective neutrophil support with just a single injection per cycle, as opposed to daily injections.

The incidence and duration of severe neutropenia (grade 4) were lower with higher doses of pegfilgrastim, indicating that pegfilgrastim can effectively reduce the severity and duration of neutropenia during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Holmes, FA., Jones, SE., O'Shaughnessy, J., et al.[2022]

Citations

1. investors.x4pharma.com investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-announces-positive-results-completed-six

Release Details - X4 Pharmaceuticals An analysis of final data from the six-month study showed that once-daily oral mavorixafor durably and meaningfully increased participants' mean absolute ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04154488

A Study of Mavorixafor in Participants With Congenital ... This is a 2-part study of mavorixafor in participants diagnosed with chronic neutropenia. The main goal of Part 1 (Phase 1b) is to help researchers learn ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11251404/

A phase 3 randomized trial of mavorixafor, a CXCR4 ... Treatment with the oral CXCR4 antagonist mavorixafor resulted in increased levels of absolute neutrophil and lymphocyte counts vs placebo.

4. checkrare.com checkrare.com/mavorixafor-for-treating-chronic-neutropenia-positive-phase-2-trial-results/

Mavorixafor for Treating Chronic Neutropenia Clinical trials have shown mavorixafor's effectiveness in this pathway. The drug maintains neutrophil counts above threshold for 15.0 hours ...

5. ashpublications.org ashpublications.org/blood/article/144/1/1/516732/Mavorixafor-a-new-hope-for-WHIM-syndrome

Mavorixafor: a new hope for WHIM syndrome | Blood Plerixafor reduced neutropenia and lymphopenia and led to wart regression. However, the requirement for twice-daily subcutaneous injections due ...

6. x4pharma.com x4pharma.com/wp-content/uploads/2023/12/ASH-2023-CN-Phase-2-Poster_Final-Updated.pdf

Preliminary Response Data and G-CSF Dose Reducti No infections were reported during the following 4 months despite some participants adjusting G-CSF dosing regimen. Safety and Tolerability.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/218709Orig1s000IntegratedR.pdf

218709Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov ... data for studies of mavorixafor in WHIM, chronic neutropenia, or oncology (see Table 3), did not identify any new or more severe safety signals than those.

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1160/504384/Mavorixafor-for-Patients-with-Chronic-Neutropenic

Mavorixafor for Patients with Chronic Neutropenic Disorders ... These preliminary data also support the safety of concomitant treatment with G-CSF and mavorixafor. Additional data from the ongoing phase 2 ...