Bone Marrow Derived Stem Cells Mobilization for Treatment of Abnormal Endometrium

Sponsor

Hugh Taylor (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05343572

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Asherman Syndrome Atrophic Endometrium Recurrent Implantation Failure	Drug: Plerixafor	Early Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a pilot, open-label, non-randomized study to investigate the use of autologous bone marrow derived stem cells (peripheral mobilization) for cell-based therapy in treating AS, AE, and RIF.This is a pilot, open-label, non-randomized study to investigate the use of autologous bone marrow derived stem cells (peripheral mobilization) for cell-based therapy in treating AS, AE, and RIF.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Endometrial Disorders Three groups of patients, with 10 subjects per group: 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. 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 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	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.

Arm

Intervention/Treatment

Experimental: Endometrial Disorders

Three groups of patients, with 10 subjects per group: 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. 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 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

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.

Outcome Measures

Primary Outcome Measures

Change in endometrial thickness and implantation rates following treatment with Plerixafor at 6 month intervals up to 24 months, compared to controls [Every 6 months from baseline up to 24 months]
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.

Secondary Outcome Measures

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 [Every 3 months from baseline up to 24 months]
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.
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 [Every 3 months from baseline up to 24 months]
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.
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 [baseline, month 3 and month 6]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy, non pregnant females
ages ≥18 and ≤40 years old at time of enrollment
with either AS, AE, or RIF

For AS: surgical history of intrauterine trauma/infection, hypo/amenorrhea, intra-uterine adhesions
for AE: US documentation of persistent, <6mm endometrial thickness
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Fertility Center	Orange	Connecticut	United States	06477

Sponsors and Collaborators

Hugh Taylor

Investigators

Principal Investigator: Hugh Taylor, MD, Yale University
Principal Investigator: Valerie A Flores, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hugh Taylor, Chair of Obstetrics, Gynecology and Reproductive Sciences, Yale University

ClinicalTrials.gov Identifier:

NCT05343572

Other Study ID Numbers:

2000026217

First Posted:

Apr 25, 2022

Last Update Posted:

Jul 15, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Hugh Taylor, Chair of Obstetrics, Gynecology and Reproductive Sciences, Yale University

bone marrow derived stem cells

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 15, 2022