Clinical trial NCT05343572: Bone Marrow Derived Stem Cells Mobilization for Treatment of Abnormal Endometrium
Official title: Bone Marrow Derived Stem Cells Mobilization for Treatment of Asherman's Syndrome, Atrophic Endometrium, and Recurrent Implantation Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Asherman Syndrome
Atrophic Endometrium
Recurrent Implantation Failure
Keywords: bone marrow derived stem cells
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2022-04-25
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in endometrial thickness and implantation rates following treatment with Plerixafor at 6 month intervals up to 24 months, compared to controls
timeFrame: Every 6 months from baseline up to 24 months
Secondary outcomes:
measure: 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
timeFrame: Every 3 months from baseline up to 24 months
measure: 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
timeFrame: Every 3 months from baseline up to 24 months
measure: 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
timeFrame: baseline, month 3 and month 6
Other outcomes:
Locations:
city: Orange
country: United States
facility: Yale Fertility Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Hugh Taylor, MD
role: PRINCIPAL_INVESTIGATOR
References: