Stem Cell Mobilization with Plerixafor for Abnormal Endometrium
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Hugh Taylor
Disqualifiers: Hydrosalpinx, Endometriosis, Diminished ovarian reserve, others
No Placebo Group
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?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. It aims to improve pregnancy chances for women with specific reproductive challenges.
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.
What data supports the effectiveness of the drug Plerixafor (Mozobil) for treating abnormal endometrium?
While there is no direct evidence for Plerixafor in treating abnormal endometrium, studies show that stem cell therapies can help improve endometrial thickness and function, which is important for fertility. Plerixafor is known to mobilize stem cells, suggesting it might support similar benefits in endometrial conditions.
12345How is the drug Plerixafor unique for treating abnormal endometrium?
Plerixafor is unique because it works by blocking a specific interaction in the body that normally keeps stem cells in the bone marrow, allowing them to move into the bloodstream. This mechanism is different from other treatments for abnormal endometrium, which may not focus on stem cell mobilization.
678910Eligibility Criteria
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 am a healthy woman, aged 18-40, not pregnant, with AS, AE, or RIF.
+1 more
Exclusion Criteria
Currently pregnant
I have been diagnosed with endometriosis through surgery.
Diminished ovarian reserve (AMH<1ng/ml or follicle stimulating hormone (FSH)>10)
+5 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Endometrial DisordersExperimental Treatment1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale Fertility CenterOrange, CT
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Who Is Running the Clinical Trial?
Hugh TaylorLead Sponsor
References
Successful derivation of xeno-free mesenchymal stem cell lines from endometrium of infertile women. [2018]Transplantation of mesenchymal stem cells (MSC) can effectively repair endometrial deficiencies, including infertile patients with a problem of inadequate endometrium thickness. Although, MSC derived from different organ sources have a similarity of MSC specific characteristics, endometrial stem cells (EMSC) are temporally regulated throughout the menstrual cycle in a micro-environmental niche found only in endometrial tissue. Given the micro-environment niche, developing treatments for endometrial disorders with EMSC should be a top priority. To provide EMSC that afford safety for therapeutic usage, we have established a completely xeno-free EMSC line derivation protocol using human allogenic umbilical cord serum instead of animal derived reagents, and proved that it is feasible to generate xeno-free EMSC lines from infertile patient donors using these conditions. Our results demonstrate the successful derivation of xeno-free EMSC lines from 10 out of 10 infertile patients. The resultant xeno-free EMSC lines showed typical MSC morphology, phenotypic markers, differentiation capacity, telomere length and normal karyotypes. They showed superior proliferation capability, but lower expression of proto-oncogenes, to the lines generated under standard (animal derived reagents) culture. Biosafety of xeno-free EMSC lines also displayed in retention of immunosuppressive ability, epigenetic stability by imprinted genes expression, proto-oncogenes expression and no mutation of specific codon on p53 tumor suppressor gene. Taken together, these data indicate that our cells may be safe for clinical use. In conclusion, we have succeeded in establishing completely xeno-free EMSC lines and demonstrate for the first time that autogenic and xeno-free EMSC lines can be generated from infertile women.
Hormone and growth factor signaling in endometrial renewal: role of stem/progenitor cells. [2022]The human endometrium is a dynamic remodeling tissue undergoing more than 400 cycles of regeneration, differentiation and shedding during a woman's reproductive years. The co-ordinated and sequential actions of estrogen and progesterone direct these major remodeling events preparing a receptive endometrium for blastocyst implantation on a monthly basis. Adult stem/progenitor cells are likely responsible for endometrial regeneration. Functional approaches have been used to identify candidate endometrial stem/progenitor cells, as there are no specific stem cell markers. Rare populations of human endometrial epithelial and stromal colony-forming cells/units (CFU) and side population (SP) cells have been identified. Several growth factors are required for CFU activity: epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) and platelet-derived growth factor BB (PDGF-BB) for both epithelial and stromal CFU, and basic fibroblast growth factor (bFGF) for stromal, but not epithelial CFU. A sub-population of human endometrial stromal cells with mesenchymal stem cell properties of CFU activity and multilineage (fat, muscle, cartilage and bone) differentiation have been isolated by their co-expression of CD146 and PDGF-receptor beta. Candidate epithelial and stromal stem/progenitor cells have been identified in mouse endometrium as rare label retaining cells (LRCs) in the luminal epithelium and as perivascular cells at the endometrial-myometrial junction, respectively. While epithelial and most stromal LRC do not express estrogen receptor alpha (Esr1), they rapidly proliferate on estrogen stimulation, most likely mediated by neighbouring Esr1-expressing niche cells. It is likely that these newly identified endometrial stem/progenitor cells may play key roles in the development of gynecological diseases associated with abnormal endometrial proliferation such as endometriosis and endometrial cancer.
G-CSF and stem cell therapy for the treatment of refractory thin lining in assisted reproductive technology. [2022]The study aims to describe two promising therapeutic options for resistant "thin" endometrium in fertility treatment: granulocyte colony-stimulating factor (G-CSF) and stem cell therapy.
Regenerative therapy by endometrial mesenchymal stem cells in thin endometrium with repeated implantation failure. A novel strategy. [2023]Our primary objective was to evaluate the endometrial changes before and after the transfer of endometrial mesenchymal stem cells (enMSCs) in a population of thinned endometrium women, with absence or hypo-responsiveness to estrogen and repeated implantation failure (RIF). The secondary objective was to evaluate the clinical outcomes of the intervention in terms of clinical pregnancy (CP), early abortions, ongoing pregnancy and live birth delivery rate (LBDR) per in vitro fertilization (IVF) cycle.
Repeated implantation failure in oocyte donation. What to do to improve the endometrial receptivity? [2016]To determine the role of polyvalent endometrial treatment in patients undergoing IVF-ET who had recurrent implantation failure (RIF) in a program of oocyte donation (OD). The results were expressed in terms of live birth rate (LBR). Secondly analyze changes of endometrial leukocyte population evaluated by flow cytometer (FC) and histopathology.
Plerixafor hydrochloride: a novel agent for the mobilization of peripheral blood stem cells. [2021]Plerixafor is a novel small molecule that inhibits CXCR4 binding to SDF-1, an interaction that is a principal regulator of hematopoietic stem cell trafficking. Phase I studies demonstrated that a single plerixafor hydrochloride dose results in a marked increase in white blood cell count and circulating CD34(+) stem cells. Subsequent single-arm and randomized clinical trials have established the efficacy of plerixafor for autologous stem cell mobilization, both combined with granulocyte colony-stimulating factor (G-CSF) and as a single agent. In December 2008 the FDA approved plerixafor in combination with G-CSF for autologous stem cell mobilization in patients with non-Hodgkin lymphoma or multiple myeloma. Plerixafor is also effective for stem cell mobilization in patients with Hodgkin lymphoma and in those who have failed a prior cytokine or chemotherapy mobilization. Preliminary studies of plerixafor in sibling donors demonstrate its efficacy for allogeneic stem cell mobilization, without any observed increase in graft failure or graft versus host disease. This review will summarize clinical trials, current use for autologous stem cell mobilization and future directions for plerixafor.
Successful mobilization of peripheral blood stem cells in children with cancer using plerixafor (Mozobil) and granulocyte-colony stimulating factor. [2021]This paper describes the successful mobilization of peripheral blood stem cells for autologous transplantation in three children with malignant diseases by using plerixafor (Mozobil; Genzyme Corporation, Cambridge, MA) and granulocyte-colony stimulating factor (G-CSF) after failed previous mobilizations. A median sixfold increase in the number of circulating CD34+ cells after plerixafor treatment as compared with the baseline level was observed. An optimal CD34+ cell count for transplantation with one or two leukapheresis sessions was achieved. Mobilization using plerixafor was found to be safe with no adverse events. Therefore, the combination of G-CSF and plerixafor in children results in effective increases in peripheral CD34+ cell counts and reduces the risk of mobilization failure.
[Mobilisation of haematopoietic stem cells with plerixafor--secondary publication]. [2021]Plerixafor (AMD3100) is a selective antagonist of a receptor expressed on haematopoietic stem cells. This receptor normally binds to a ligand on bone marrow stromal cells, responsible for the homing and keeping the stem cells in place. Plerixafor has been successfully used in clinical trails in patients with malignant lymphoma and multiple myeloma, where mobilization of stem cells with granulocyte colony-stimulating factor for leukapheresis and later stem cell transplantation were not possible. Plerixafor has also been given with success to healthy donors for harvest and haematopoietic allograft.
Optimizing mobilization strategies in difficult-to-mobilize patients: The role of plerixafor. [2021]Peripheral blood stem cell collection is currently the most widely used source for hematopoietic autologous transplantation. Several factors such as advanced age, previous chemotherapy, disease and marrow infiltration at the time of mobilization influence the efficacy of CD34(+) progenitor cell mobilization. Despite the safety and efficiency of the standard mobilization protocols (G-CSF ± chemotherapy), there is still a significant amount of mobilization failure rate (10-40%), which necessitate novel agents for effective mobilization. Plerixafor, is a novel agent, has been recently approved for mobilization of hematopoietic stem cells (HSCs). The combination of Plerixafor with G-CSF provides the collection of large numbers of stem cells in fewer apheresis sessions and can salvage those who fail with standard mobilization regimens. The development and optimization of practical algorithms for the use Plerixafor is crucial to make hematopoietic stem cell mobilization more efficient in a cost-effective way. This review is aimed at summarizing how to identify poor mobilizers, and define rational use of Plerixafor for planning mobilization in hard-to-mobilize patients.
New strategies for stem cell mobilization. [2021]Mobilized peripheral blood (PB) is widely used as source of stem cells (PBSCs) for autologous stem cell transplantation (ASCT). The use of cytokines, alone or in combination with chemotherapy (chemomobilization), is the most common strategy applied to mobilize and collect PBSCs. However, a significant proportion of cancer patients fail to mobilize enough PBSCs to proceed to ASCT. Plerixafor is a small molecule that reversibly and transiently disrupts the interaction between the chemokine receptor CXCR4 and its ligand CXCL12 (formerly known as stroma derived factor 1, SDF-1) leading to the rapid release of CD34(+) hematopoietic stem cells from the bone marrow (BM) to PB. Plerixafor has been recently approved to enhance PBSC mobilization in adult patients with multiple myeloma or non-Hodgkin lymphoma and has been shown to be more effective than G-CSF alone. There is limited experience on combining plerixafor with chemotherapy plus G-CSF in patients who mobilize poorly. Current evidence suggests that the addition of plerixafor is safe and effective in the large majority of the patients with low blood CD34(+) cell count after mobilization and/or poor yield after the first collection(s). Circulating CD34(+) cells can be increased by several folds with plerixafor and the majority of the patients considered "poor mobilizers" can be successfully collected. Overall, its mechanism of action inducing the rapid release of CD34(+) cells from the BM to the circulation makes plerixafor suitable for the 'preemptive' use in patients who are hard-to-mobilize.