Bone Marrow Derived Stem Cells Mobilization for Treatment of Abnormal Endometrium

Hugh Taylor

Status and phase: Enrolling; Early Phase 1

Conditions: Atrophic Endometrium; Recurrent Implantation Failure; Asherman Syndrome

Treatments: Drug: Plerixafor

Study type: Interventional

Funder types: Other

Identifiers

NCT05343572

No NIH funding (Other Identifier)

2000026217

Details and patient eligibility

About

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).

Full 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.

Enrollment: 90 estimated patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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90 participants in 1 patient group

Endometrial Disorders

Experimental group

Description:

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

Treatment:

Drug: Plerixafor