Vulvovaginal Graft-versus-Host Disease: Diagnosis and Microbiome Evaluation

The goal of this observational study is to investigate the development of vulvovaginal graft-versus-host- disease (GVHD), an under-reported and under-recognized manifestation of chronic GVHD. This study aims to characterize the vaginal microbiome in participants undergoing allogeneic hematopoietic cell transplantation (HCT). The main questions it aims to answer are:

• Is the vaginal microbiome altered during allogeneic HCT?
• What changes may help researchers understand the development of vulvovaginal GVHD?

Participants will be asked to undergo an assessment of vulvovaginal symptoms through a vulvovaginal symptom questionnaire once pre-transplant, 6 months post-transplant, and twelve12 months post- transplant. Participants will also be asked to undergo a vaginal microbiome (collection of bacteria, fungi, and viruses that live on our bodies) evaluation through a vaginal exam performed by a gynecologist with collection of vaginal samples once pre-transplant and again six months post-treatment and twelve months post-transplant. If a participant develops symptoms of vulvovaginal GVHD at any point in time during the post-transplant follow up, the participant may partake in additional vaginal exams to diagnose GVHD at the time of symptom onset.

Study Overview

• Status: Recruiting
• Conditions: Vulvovaginal Signs and Symptoms; Graft Vs Host Disease
• Intervention / Treatment: Other: Vulvovaginal Symptom Questionnaire; Diagnostic test: Vaginal Microbiome Evaluation

Detailed Description

Recent advances in technologies including high throughput metagenomic 16S rRNA gene sequencing have revealed a larger, more complex picture of the bacterial diversity in the genital tract and unique microbial communities not previously recognized among the known vaginal flora categories. Little is known about how the vaginal microbiome protects the female genital tract or other roles it may have, including interacting with the microbiota of other body sites and subsequent inflammatory responses. Alteration of vaginal flora may play a part in the pathogenesis of diseases by modulating immunity or increasing the growth of pathogenic strains. Recent research has been conducted regarding changes in the vaginal microbiome during various infectious and inflammatory states such as bacterial vaginosis, pelvic inflammatory disease, sexually transmitted infectious, and pregnancy. However, the vaginal microbiome during allogeneic HCT and development of genital GVHD has yet to be examined. Thus, the role of the vaginal microbiome in the development of genital GVHD is a critical area of study.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Betty K Hamilton, MD; Phone Number: 1-866-223-8100; Email: TaussigResearch@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
      • Contact: Betty, MD; Phone Number: 866-223-8100; Email: TaussigResearch@ccf.org
      • Principal Investigator: Betty K Hamilton, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Female participants undergoing allogenic HCT will be recruited from the Blood and Marrow Transplant Program at the Cleveland Clinic.

Description

Inclusion Criteria:

• Female participants planning to undergo allogeneic HCT for any disease indication, OR, female participants who have already received HCT and have developed vulvovaginal GVHD during their post-transplant follow-up period
• All conditioning regimens (myeloablative or reduced intensity) will be included.
• All donor sources (HLA matched/mismatched related, unrelated, umbilical cord, haploidentical) will be included.
• All graft sources (bone marrow or peripheral blood stem cells) will be included.
• All GVHD prophylaxis regimens will be included.
• Aged 18-70.
• English speaking and able to sign written informed consent.
• Participants agree to a vaginal gynecologic exam.
• Co-enrollment on other clinical trials will be allowed.

Exclusion Criteria:

• Participants who decline or unable to undergo vaginal gynecologic exam due to any discomfort or pain.
• Any concurrent medical, psychiatric or other illness in which the provider believes the participants may not be able to comply with study assessments.
• Participants with a current diagnosis of a sexually transmitted infection (STI) (Herpes Simplex Virus, Gonorrhea, Chlamydia, Trichomonas,) or a history of previously untreated STI which may incite inflammation that will impact the microbiome.
• Participants with a history of lichen sclerosis, lichen planus, pre-transplant.
• Participants with a history or current diagnosis of vaginal or vulvar malignancy.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Allogeneic HCT participants; The cohort will be comprised of participants undergoing allogeneic HCT at the Cleveland Clinic.

Other: Vulvovaginal Symptom Questionnaire; Participants will undergo assessment of vulvovaginal symptoms via the vulvovaginal questionnaire once pre-transplant, six months, and develop months post-transplant.; Diagnostic test: Vaginal Microbiome Evaluation; A vaginal microbiome evaluation will be performed via vaginal exam by a gynecologist with collection of vaginal samples once pre-transplant, six months, and twelve months post-transplant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the vaginal microbiome profile of female participants undergoing allogeneic HCT	A primary objective of this study is to characterize the vaginal microbiome and in female participants undergoing allogeneic HCT.	Up to twelve months post-transplant
Characterize the change in vaginal microbiome profile of female participants undergoing allogeneic HCT	A primary objective of this study is to characterize the vaginal microbiome change in female participants undergoing allogeneic HCT.	Up to twelve months post-transplant
Incidence of vulvovaginal GVHD	A primary objective is to measure the incidence of vulvovaginal GVHD in this cohort.	Up to twelve months post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the differences in vaginal microbiome between participants who develop vulvovaginal GVHS versus those who do not	The secondary objective is to investigate differences in vaginal microbiome between participants who develop vulvovaginal GVHD and those who do not.	Up to twelve months post-transplant

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: Betty K Hamilton, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: October 17, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HCT; GVHD; Allogeneic Hematopoietic Cell Transplantation; Vaginal Microbiome; Vulvovaginal GVHD; Vulvovaginal graft-versus-host disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: CASE2Z24

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