Bone Marrow Derived Stem Cells Mobilization for Treatment of Abnormal Endometrium

Recurrent Implantation Failure Clinical Trial

Official title:

Bone Marrow Derived Stem Cells Mobilization for Treatment of Asherman's Syndrome, Atrophic Endometrium, and Recurrent Implantation Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05343572
• Other study ID #: 2000026217
• Secondary ID: No NIH funding
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 1, 2023
• Est. completion date: December 2026

Study information

• Verified date: November 2023
• Source: Yale University
• Contact: Hugh S Taylor, MD
• Phone: (203)-785-6949
• Email: hugh.taylor[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the use of autologous bone marrow stem cells mobilization using 1,1'-[1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane (PLERIXAFOR) as an effective medical therapy for the treatment of Asherman's Syndrome (AS), Atrophic Endometrium (AE) and Recurrent Implantation Failure (RIF).

Description:

This study will assess the use of autologous bone marrow stem cells mobilization using 1,1'-[1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane (PLERIXAFOR) as an effective medical therapy for the treatment of Asherman's Syndrome (AS), Atrophic Endometrium (AE) and Recurrent Implantation Failure (RIF).

Primary Objective:

• To compare endometrial thickness and implantation rates in women with AS, AE, and RIF receiving PLERIXAFOR compared to historic controls that received existing standard of care therapy

• To compare ongoing pregnancy and live birth rates in women with AS, AE, and RIF receiving PLERIXAFOR compared to historic controls that received existing standard of care therapy

Secondary Objectives: (assessed in participants who have not achieved pregnancy as of the timepoint):

• Endometrial thickness prior to treatment with PLERIXAFOR compared to endometrial thickness 3 and 6 months after treatment.

During this study, participants are asked to:

• Refrain from use of non-steroidal anti-inflammatory drugs (NSAIDs) from 2 weeks prior to the start of the surgery/PLERIXAFOR administration, and for the 30 days following surgery/ PLERIXAFOR administration.

• Abstain from intercourse for three months following surgery/PLERIXAFOR administration

• Assessment of menstrual bleeding pattern before and 3 and 6 months following treatment with PLERIXAFOR

• Assessment of endometrial blood flow before and 3 and 6 months following treatment with PLERIXAFOR

• Assessment of endometrial histology three months following treatment with PLERIXAFOR The study intervention consists of administration of PLERIXAFOR the evening prior to scheduled standard of care surgery for women with AS, AE or RIF, for peripheral mobilization of stem cells. PLERIXAFOR is administered via the subcutaneous route, as a single dose of 20mg.

The goal of this study is to determine if the administration of PLERIXAFOR for autologous, peripheral stem cell mobilization and administration will restore endometrial function in women with AS, AE, and RIF, and allow for pregnancy implantation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy, non pregnant females

• ages =18 and =40 years old at time of enrollment

• with either AS, AE, or RIF

1. For AS: surgical history of intrauterine trauma/infection, hypo/amenorrhea, intra-uterine adhesions

2. for AE: US documentation of persistent, <6mm endometrial thickness

3. for RIF: failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under 40 years and currently being treated at Yale Fertility Clinic

Exclusion Criteria:

• Presence of hydrosalpinx (diagnosed by radiographic or ultrasound imaging)

• Endometriosis (diagnosed by previous surgery,)

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

• History of genital tuberculosis or any ultrasound evidence of congenital uterine anomaly

• Submucous or intracavitary fibroid, polyps

• Currently pregnant

• Personal history of thrombophilia or sickle cell disease

• Inability to provide informed consent

Related Conditions & MeSH terms

• Asherman Syndrome
• Atrophy
• Recurrent Implantation Failure
• Syndrome

Intervention

Drug:
• Plerixafor
A 20mg single dose of PLERIXAFOR is administered subcutaneously the evening prior to scheduled standard of care surgery for women with AS, AE or RIF for peripheral mobilization of stem cells. For subjects weighing >83 kilogram, the dosing is a single dose of 0.24 milligram per kilogram.

Locations

Country	Name	City	State
United States	Yale Fertility Center	Orange	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Hugh Taylor

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in endometrial thickness and implantation rates following treatment with Plerixafor at 6 month intervals up to 24 months, compared to controls	Change in endometrial thickness post treatment compared to historic controls that received existing standard of care therapy, measured using ultrasound. Thicker endometrium (>6mm) indicates restoration of endometrial function.	Every 6 months from baseline up to 24 months
Secondary	Change in endometrial thickness and implantation rates with Plerixafor in women with AS, AE and RIF at 3 month intervals, compared to baseline/pre-treatment	Change in endometrial thickness and implantation rates with Plerixafor in women with AS, AE and RIF at 3 month intervals, compared to baseline/pre-treatment will be assessed. Less atrophy, less fibrosis, greater blood vessel formation and greater endometrial blood flow on ultrasound, compared to historic controls is indicative of restoration of endometrial function.	Every 3 months from baseline up to 24 months
Secondary	Difference in ongoing pregnancy and live birth rates in women with AS, AE and RIF following treatment with Plerixafor at 3 month intervals, compared to baseline/pre-treatment	The difference in ongoing pregnancy and live birth rates in women with AS, AE and RIF following treatment with Plerixafor at 3 month intervals, compared to baseline/pre-treatment will be assessed. Less atrophy, less fibrosis, greater blood vessel formation and greater endometrial blood flow on ultrasound, compared to historic controls is indicative of restoration of endometrial function.	Every 3 months from baseline up to 24 months
Secondary	Change in endometrial thickness from baseline after treatment with Plerixafor at month 3 and month 6 for participants that have not achieved pregnancy as of the timepoint	Change in endometrial thickness from baseline after treatment with Plerixafor compared to month 3 and month 6 measured using ultrasound. Thicker endometrium (>6mm) indicates restoration of endometrial function.	baseline, month 3 and month 6