FMT In High-Risk Acute GVHD After ALLO HCT

Fecal Microbiota Transplantation (FMT) in for the Treatment of High-Risk Acute Graft-Versus-Host Disease (GVHD) After Allogeneic Hematopoietic Cell Transplantation (HCT)

The purpose of this study is to evaluate the effectiveness of Fecal Microbiota Transplant (FMT) treatment in high-risk acute graft-versus-host disease (GVHD).

This research study involves an experimental intervention called FMT.

Study Overview

• Status: Completed
• Conditions: Hematopoietic Cell Transplantation; Acute Graft-Versus-Host Disease (Gvhd) Grade; Fecal Microbiota Transplant
• Intervention / Treatment: Biological: Fecal Microbiota Transplant

Detailed Description

In this research study, the investigators are evaluating the effectiveness of Fecal Microbiota Transplant (FMT) treatment in high-risk acute GVHD. The investigators are evaluating the effectiveness of FMT (also known as 'stool transplantation' or 'fecal transplant') in being able to transfer gut organisms from a healthy donor to the patient.

The investigators are also evaluating the ability of this treatment to improve or completely resolve the clinical symptoms (diarrhea, abdominal pain, rash, liver inflammation) that can occur with acute GVHD.This research study is a Pilot Study, which is the first time investigators are examining this intervention for treatment of acute GVHD.

The FDA (the U.S. Food and Drug Administration) has not approved FMT for this use. The FDA has classified human stool as a biological agent and determined that its use in FMT therapy should be regulated to ensure patient safety. To use FMT to treat recurrent Clostridium difficile infection, the most common indication for FMT, does not require an investigation new drug permit. To use FMT for research or to treat any condition other than recurrent Clostridium difficile infection requires an investigation new drug permit. An investigation new drug permit has been obtained for this study.

• After HCT, the body's microbiome (the natural existence of various bacteria and organisms) in the intestinal tract may be affected, in that the number and types of good bacteria is reduced (also called a reduction in microbial flora diversity). Studies have shown that the number and types of good bacteria in the gut can impact whether or not graft-versus-host disease (GVHD) is developed. GVHD occurs when donated bone marrow cells attack the body with an immune response.
• FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur the body. Since may have decreased microbial flora diversity after HCT, these microbial components are taken from a stool donor. They are extracted from fecal matter (stool) and put into a capsule to ingest.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women ≥ 18 years old
• Patient has undergone allogeneic hematopoietic cell transplantation from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
• Evidence of myeloid engraftment (eg, absolute neutrophil count ≥ 0.5 × 109/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed.

• Patient must have clinically suspected Grade II to IV aGVHD as per MAGIC criteria. Clinical suspicion of aGVHD by the treating physician is sufficient and biopsies are not required to pathologically confirm aGVHD. However, in situations where alternative diagnoses of drug effects or infection are not adequately ruled out on clinical suspicion alone, biopsies are recommended. - Patients must have a diagnosis of high-risk acute GVHD, defined as either:

  -- Steroid-refractory GVHD:

  • Progressive GVHD after at least 3 days of systemic corticosteroids (≥ 1 mg/kg/day of prednisone equivalent), OR
  • No improvement in GVHD after at least 7 days on ≥ 1 mg/kg/day of prednisone equivalent or insufficient improvement which warrants the addition of another agent, OR
  • Flare of GVHD symptoms during taper.

• High-risk, treatment-naïve GVHD

  • AA3 risk by Ann Arbor GVHD scoring risk system
  • Treatment-naïve: less than 3 days of therapy with systemic corticosteroids (≥ 1 mg/kg/day of prednisone equivalent)
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for 3 months after FMT.
• Ability to understand and the willingness to sign a written informed consent document, including the willingness to accept risk of unrelated donor stool.
• Ability to swallow large capsules.

Exclusion Criteria:

• Participants who have initiated a new systemic treatment for steroid-refractory GVHD (institutional standard or investigational agent) within the 2 weeks prior to first dose of FMT. Treatment with FMT is allowed once the time since initiation of newest systemic therapy is 2 weeks or longer.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Delayed gastric emptying syndrome or large hiatal hernia
• Known chronic aspiration
• Participants with a history of significant allergy to foods not excluded from the donor diet (excluded foods are tree nuts, peanuts, shellfish, eggs)
• Pregnant and breast-feeding women are ineligible because they are not eligible for hematopoietic stem cell transplantation.
• HIV-positive participants are ineligible.
• Participants who are unable to swallow pills.
• Participants with end-stage liver disease (cirrhosis)
• Participants with acute, active gastrointestinal infection (e.g., typhlitis, diverticulitis, appendicitis)
• Participants with inflammatory bowel disease (e.g., ulcerative colitis, Crohn's)
• Prior total colectomy

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: Fecal Microbiota Transplant (FMT) FOR HIGH-RISK ACUTE GVHD; The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. this research study for up to 6 months. You may receive up to 2 cycles of the study treatment. - Fecal Microbiota Transplant ( FMT)- Oral Study Drug, predetermined dosage and timings, up to 2 cycles.; One cycle of treatment consists of one induction week of FMT followed by three weeks of maintenance FMT.; The maintenance weeks happen for 3 weeks after the induction week.; All doses will be administered in the clinic.; A second cycle of treatment as deemed appropriate

Biological: Fecal Microbiota Transplant; FMT- Oral Study Drug, predetermined dosage and timings, up to 2 cycles; Other Names: FMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who are able to swallow ≥ 40 capsules (out of 75)	Based on this information, FMT will be considered feasible if, among the 11 eligible patients, ≥8 patients are able to swallow ≥ 40 capsules.	29 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate-Acute GVHD	Kaplan-Meier estimates	29 Days
Overall Survival	Kaplan-Meier estimates	6 months, 12 Months
Progression Free Survival	Kaplan-Meier estimates	6 months, 12 Months
Non-relapse mortality (NRM)	time from first dose of FMT to death without relapse or progression or underlying disease. Deaths from any cause without prior progression are considered as NRM events	6 month, 12 Months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: American Cancer Society, Inc.
• Investigators: Principal Investigator: Zachariah DeFilipp, MD, Masachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2021
• Primary Completion (Actual): August 3, 2022
• Study Completion (Actual): January 5, 2023

Study Registration Dates

• First Submitted: October 23, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplant; Hematopoietic Cell Transplantation; Acute Graft-Versus-Host Disease (Gvhd) Grade
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: 19-359

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to the Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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