Bone Marrow Derived Stem Cells Mobilization for Treatment of Abnormal Endometrium

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

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).

Study Overview

• Status: Recruiting
• Conditions: Asherman Syndrome; Recurrent Implantation Failure; Atrophic Endometrium
• Intervention / Treatment: Drug: Plerixafor

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Michele Frank, BSN; Phone Number: (203)-785-2164; Email: Michele.Frank@yale.edu
• Study Contact Backup: Name: Hugh S Taylor, MD; Phone Number: (203)-785-6949; Email: hugh.taylor@yale.edu

Study Locations

• United States
  • Connecticut
    • Orange, Connecticut, United States, 06477
      • Recruiting
      • Yale Fertility Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 cycleDay of human chorionic gonadotropin (hCG) trigger in the setting of fresh IVF cycleDay 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Hugh Taylor
• Investigators: Principal Investigator: Hugh Taylor, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: bone marrow derived stem cells
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Pathological Conditions, Anatomical; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Syndrome; Atrophy; Gynatresia; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Plerixafor
• Other Study ID Numbers: 2000026217; No NIH funding (Other Identifier: 10.11.23)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No