FMT In High-Risk Acute GVHD After ALLO HCT

NCT04139577 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 19-359
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Graft-Versus-Host Disease (Gvhd) Grade; Hematopoietic Cell Transplantation; Fecal Microbiota Transplant

Keywords

Acute Graft-Versus-Host Disease (Gvhd) Grade; Hematopoietic Cell Transplantation; Fecal Microbiota Transplant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Response Rate-Acute GVHD

  29 Days

• Overall Survival

  6 months, 12 Months

• Progression Free Survival

  6 months, 12 Months

• Non-relapse mortality (NRM)

  6 month, 12 Months

Study Arms (1)

Fecal Microbiota Transplant (FMT) FOR HIGH-RISK ACUTE GVHD

EXPERIMENTAL

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

Interventions

Fecal Microbiota Transplant BIOLOGICAL

FMT- Oral Study Drug, predetermined dosage and timings, up to 2 cycles

Also known as: FMT

Fecal Microbiota Transplant (FMT) FOR HIGH-RISK ACUTE GVHD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• American Cancer Society, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• DeFilipp Z, Damania AV, Kim HT, Chang CC, El-Jawahri A, McAfee SL, Bottoms AS, Toncheva V, Smith MM, Dolaher M, Perry L, White M, Diana B, Connolly S, Dey BR, Frigault MJ, Newcomb RA, O'Donnell PV, Spitzer TR, Mansour MK, Weber D, Ajami NJ, Hohmann E, Jenq RR, Chen YB. Third-party fecal microbiota transplantation for high-risk treatment-naive acute GVHD of the lower GI tract. Blood Adv. 2024 May 14;8(9):2074-2084. doi: 10.1182/bloodadvances.2024012556.

  PMID: 38471063 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Zachariah DeFilipp, MD

  Masachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: October 25, 2019
• Study Start: June 18, 2021
• Primary Completion: August 3, 2022
• Study Completion: January 5, 2023
• Last Updated: March 7, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)