Stem Cell Mobilization with Plerixafor for Abnormal Endometrium

Overseen By Michele Frank, BSN

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Hugh Taylor

Disqualifiers: Hydrosalpinx, Endometriosis, Diminished ovarian reserve, 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: 4

Duration: 1 day

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Plerixafor (also known as Mozobil) can improve the thickness and health of the uterine lining in women with certain reproductive issues. It focuses on three conditions: Asherman's Syndrome (scar tissue in the uterus), Atrophic Endometrium (a thin uterine lining), and Recurrent Implantation Failure (difficulty getting pregnant after multiple embryo transfers). Women who may be suitable candidates are those trying to conceive and have one of these conditions, which impacts their daily lives and hopes for a family. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to be among the first to potentially benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that plerixafor is usually well-tolerated when used to mobilize stem cells. In past studies, most participants experienced only mild side effects, such as nausea or headaches, while serious side effects were rare. Plerixafor has also been used safely in other contexts, such as during stem cell transplants, supporting its safety profile. However, since this trial is in an early stage, researchers are still assessing its safety for the specific conditions under study. Participants will be monitored closely to address any side effects promptly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometrial disorders?

Researchers are excited about Plerixafor for treating abnormal endometrium because it offers a unique approach compared to current options like hormonal therapies and surgical interventions. Unlike these standard treatments, Plerixafor works by mobilizing stem cells, which may help repair and regenerate the endometrial lining. This new mechanism of action could potentially improve outcomes for patients with conditions like refractory Asherman's syndrome, atrophic endometrium, and recurrent implantation failure, where traditional treatments have limited success. By targeting the underlying cause of the problem, Plerixafor provides a promising new avenue for patients struggling with these challenging endometrial disorders.

What evidence suggests that Plerixafor might be an effective treatment for Asherman's Syndrome, Atrophic Endometrium, and Recurrent Implantation Failure?

Research has shown that Plerixafor can mobilize a person's own stem cells to potentially repair the uterine lining. This trial examines Plerixafor for conditions such as Asherman's Syndrome, thin uterine lining, and repeated embryo implantation failure. Early results suggest that mobilizing stem cells into the bloodstream might enhance the uterine lining. Although human studies provide limited data, the concept is that these stem cells can repair tissue and improve pregnancy chances. This method remains under investigation, but it is based on the promising idea of using the body's own resources for healing. ^{1 2 6 7 8}

Who Is on the Research Team?

Hugh Taylor, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for healthy, non-pregnant women aged 18-40 with Asherman's Syndrome (AS), Atrophic Endometrium (AE), or Recurrent Implantation Failure (RIF). Participants must have specific conditions like a thin endometrium (<6mm) or history of failed embryo transfers. Women with diminished ovarian reserve, current pregnancy, endometriosis, genital tuberculosis, thrombophilia, sickle cell disease, hydrosalpinx or uterine anomalies cannot join.

Inclusion Criteria

I've had at least 4 good-quality embryos transferred without pregnancy, under 40, treated at Yale.

For AE: US documentation of persistent, <6mm endometrial thickness

I have had surgery related to internal uterine issues, including trauma, infection, or adhesions.

Exclusion Criteria

Currently pregnant

I have been diagnosed with endometriosis through surgery.

Diminished ovarian reserve (AMH<1ng/ml or follicle stimulating hormone (FSH)>10)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Administration of PLERIXAFOR for autologous, peripheral stem cell mobilization to restore endometrial function

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in endometrial thickness, implantation rates, and other outcomes at 3-month intervals

24 months

Every 3 months (in-person)

Long-term follow-up

Assessment of ongoing pregnancy and live birth rates, and endometrial function restoration

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Plerixafor

Trial Overview The study tests the effectiveness of Plerixafor to mobilize autologous bone marrow stem cells as a treatment for AS, AE and RIF in women. It aims to see if this approach can improve the condition of the endometrium and increase chances of successful implantation.

How Is the Trial Designed?

Group I: Endometrial Disorders Experimental Treatment 1 Intervention

Three groups of patients, with 10 subjects per group: 1. Asherman's syndrome, as classified by the American Society of Reproductive Medicine (ASRM) by extent of uterine cavity involvement and adhesion type. Specifically, refractory Asherman's syndrome: patients who have had at least one operative hysteroscopy which was unsuccessful. 2. Atrophic endometrium, as defined by maximal endometrial lining thickness ≤6mm documented in at least 2 cycles on either: * Day of luteinizing hormone (LH) surge in natural cycle * Day of human chorionic gonadotropin (hCG) trigger in the setting of fresh IVF cycle * Day 14 of estradiol in the setting of frozen embryo transfer things (FET) cycles 3. Recurrent implantation failure, defined as failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen transfer cycles in a woman under 40 years

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

Approved in European Union as Mozobil for:

• Autologous stem cell transplantation for patients with lymphoma and multiple myeloma

Approved in United States as Mozobil for:

• Use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM)

Who Is Running the Clinical Trial?

Hugh Taylor

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

Plerixafor is an effective and safe treatment for enhancing the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma or non-Hodgkin lymphoma, especially those who struggle to mobilize enough cells for autologous stem cell transplantation (ASCT).

By disrupting the interaction between the CXCR4 receptor and its ligand, plerixafor significantly increases the number of circulating CD34(+) hematopoietic stem cells, making it a valuable option for patients identified as 'poor mobilizers' after initial mobilization attempts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New strategies for stem cell mobilization. Lemoli, RM.[2021]

Plerixafor is a newly approved agent that, when combined with G-CSF, significantly improves the mobilization of hematopoietic stem cells, allowing for larger collections in fewer sessions, especially for patients who struggle with standard mobilization methods.

Despite the effectiveness of standard mobilization protocols, there is still a 10-40% failure rate, highlighting the need for agents like Plerixafor to enhance stem cell collection in patients with factors that complicate mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing mobilization strategies in difficult-to-mobilize patients: The role of plerixafor. Goker, H., Etgul, S., Buyukasik, Y.[2021]

A new protocol was developed to derive completely xeno-free endometrial stem cell (EMSC) lines from 10 infertile patients, ensuring safety for therapeutic use by avoiding animal-derived reagents.

The xeno-free EMSC lines demonstrated typical stem cell characteristics, superior proliferation, and maintained biosafety features, including low proto-oncogene expression and no mutations in the p53 tumor suppressor gene, indicating their potential for clinical applications in treating endometrial deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful derivation of xeno-free mesenchymal stem cell lines from endometrium of infertile women. Phermthai, T., Tungprasertpol, K., Julavijitphong, S., et al.[2018]

In a study involving women with thinned endometrium and repeated implantation failure, the transfer of endometrial mesenchymal stem cells (enMSCs) significantly increased endometrial thickness from an average of 5.24 mm to 9.93 mm, indicating improved endometrial health.

The intervention led to a clinical pregnancy rate of 79.31% and a live birth delivery rate of 45.45% per embryo transfer, suggesting that enMSC treatment enhances the chances of successful pregnancies in IVF cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regenerative therapy by endometrial mesenchymal stem cells in thin endometrium with repeated implantation failure. A novel strategy. Tersoglio, AE., Tersoglio, S., Salatino, DR., et al.[2023]

Plerixafor (AMD3100) effectively mobilizes hematopoietic stem cells by blocking their receptor, which normally keeps them anchored in the bone marrow, making it useful for patients with malignant lymphoma and multiple myeloma who need stem cell transplantation.

In clinical trials, Plerixafor has also been successfully used in healthy donors to facilitate stem cell harvesting for allogeneic transplants, demonstrating its safety and efficacy in both patient and donor populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mobilisation of haematopoietic stem cells with plerixafor--secondary publication]. Hansen, PB., Gaarsdal, E.[2021]

Plerixafor is an effective small molecule that enhances the mobilization of hematopoietic stem cells, significantly increasing white blood cell counts and circulating CD34(+) stem cells, as demonstrated in Phase I studies.

The FDA approved plerixafor in December 2008 for use with G-CSF in autologous stem cell mobilization for patients with non-Hodgkin lymphoma or multiple myeloma, and it has also shown efficacy in patients with Hodgkin lymphoma and those who did not respond to previous mobilization attempts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plerixafor hydrochloride: a novel agent for the mobilization of peripheral blood stem cells. Cashen, AF.[2021]

Intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) has shown significant benefits in improving endometrial thickness and increasing pregnancy rates in patients with a thin endometrium, which is crucial for embryo implantation.

Stem cell therapy is emerging as a promising treatment option for patients with severely refractory thin endometrium, although more research is needed to fully establish its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

G-CSF and stem cell therapy for the treatment of refractory thin lining in assisted reproductive technology. Mouhayar, Y., Sharara, FI.[2022]

The human endometrium undergoes significant remodeling driven by estrogen and progesterone, with adult stem/progenitor cells playing a crucial role in its regeneration during the reproductive years.

Recent studies have identified specific populations of endometrial stem/progenitor cells, which may contribute to gynecological diseases like endometriosis and endometrial cancer, highlighting their potential importance in understanding and treating these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormone and growth factor signaling in endometrial renewal: role of stem/progenitor cells. Gargett, CE., Chan, RW., Schwab, KE.[2022]

In a study of 75 patients with recurrent implantation failure undergoing oocyte donation, a polyvalent endometrial treatment significantly improved endometrial thickness and reduced abnormal histopathological findings, which are crucial for successful implantation.

The treatment also led to changes in the endometrial leukocyte population, indicating a potential mechanism for improving implantation rates, although the increase in uterine killer cells was noted in the absence of pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated implantation failure in oocyte donation. What to do to improve the endometrial receptivity? Tersoglio, AE., Salatino, DR., Reinchisi, G., et al.[2016]

In a study involving three children with malignant diseases, the combination of plerixafor and G-CSF successfully mobilized peripheral blood stem cells for autologous transplantation after previous mobilization attempts had failed.

Plerixafor treatment resulted in a median sixfold increase in circulating CD34+ cells, was found to be safe with no adverse events, and effectively reduced the risk of mobilization failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful mobilization of peripheral blood stem cells in children with cancer using plerixafor (Mozobil) and granulocyte-colony stimulating factor. Avramova, BE., Yordanova, MN., Konstantinov, DN., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05343572

Bone Marrow Derived Stem Cells Mobilization for ... The goal of this study is to determine if the administration of PLERIXAFOR for autologous, peripheral stem cell mobilization and administration will restore ...

2. withpower.com withpower.com/trial/early-phase-1-ashermans-syndrome-3-2022-1687d

Stem Cell Mobilization with Plerixafor for Abnormal ... This trial tests if a new treatment can help women with uterine lining issues by moving their own stem cells into their blood to repair the uterus.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05343572?term=AREA%5BConditionSearch%5D(%22Asherman's%20Syndrome%22)&rank=7

Bone Marrow Derived Stem Cells Mobilization for ... The goal of this study is to determine if the administration of PLERIXAFOR for autologous, peripheral stem cell mobilization and administration will restore ...

4. yalemedicine.org yalemedicine.org/clinical-trials/bone-marrow-derived-stem-cells-mobilization-for-treatment-of-as-ae-and-rif

Bone Marrow Derived Stem Cells Mobilization for treatment ... Bone Marrow Derived Stem Cells Mobilization for treatment of Asherman's syndrome, Atrophic endometrium, and Recurrent implantation failure.

5. dev-multi-sponsor-trials.xogene.com dev-multi-sponsor-trials.xogene.com/trials/5343572

Bone Marrow Derived Stem Cells Mobilization for ... - GoodDay ... (PLERIXAFOR) as an effective medical therapy for the treatment of Asherman's Syndrome (AS), Atrophic Endometrium (AE) and Recurrent Implantation Failure (RIF).

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05343572/bone-marrow-derived-stem-cells-mobilization-for-treatment-of-abnormal-endometrium

Bone Marrow Derived Stem Cells Mobilization for ... ... effective medical therapy for the treatment of Asherman's Syndrome (AS), Atrophic Endometrium (AE) and Recurrent Implantation Failure (RIF).

7. medchemexpress.com medchemexpress.com/Plerixafor.html?srsltid=AfmBOoqbSokkl-4sphznVDhg5KLhoX93bhOZfrWIdeEtae3Zb_829fD9

Plerixafor (AMD 3100) | CXCR4 Antagonist Asherman Syndrome|Atrophic Endometrium|Recurrent Implantation Failure. 2023 ... SAFETY DATA SHEET (SDS). English - EN (393 KB) Français - FR (393 KB) ...

8. smartpatients.com smartpatients.com/trials/NCT05343572

Bone Marrow Derived Stem Cells Mobilization for ... Conditions. Asherman Syndrome, Atrophic Endometrium, Recurrent Implantation Failure. Treatments. Plerixafor. Summary. This study will assess the ...