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Fecal Microbiota Transplantation For The Treatment Of Gastro-Intestinal Acute GVHD

Primary Purpose

Gastro-Intestinal Acute Graft Versus Host Disease (GI-aGVHD)

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fecal Microbiota Transplantation (FMT)

About this trial

This is an interventional treatment trial for Gastro-Intestinal Acute Graft Versus Host Disease (GI-aGVHD) focused on measuring Graft Versus Host Disease (GVHD)

Eligibility Criteria

19 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

One of the following diagnosis:
High risk aGVHD (either biopsy proven or clinical diagnosed) (see Appendix B & C) as defined by either:
- Lower gastrointestinal (GI) stage 3+
- Hyper-acute GVHD as defined by aGVHD of the GI tract within the first 14 days of transplant AND
- Subjects with treatment-naive acute GVHD as defined as those who have not received previous systemic treatment for acute GVHD, except for a maximum of 7 days of no less than 1 mg/kg/day of methyl-prednisolone (or equivalent dose of prednisone).

OR:

Steroid refractory aGVHD of the GI tract (either biopsy proven or clinical diagnosed) as defined by:
- no response to steroid treatment (minimum daily dose: 2 mg/kg methyl-prednisolone or equivalent) lasting at least 7 days, or
- progression of at least one grade within the first 72 h of treatment
ECOG Performance status < 3
Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source.
Patients who are able stop prophylactic antibiotics during the treatment period
Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Active malignancy
Patients with any concurrent uncontrolled clinically significant medical condition including active infection, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
Pregnant or breastfeeding women
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds
Patients with any severe gastrointestinal condition other than GI-GVHD.
Inability (e.g. dysphagia) to or unwilling to swallow capsules
Active gastrointestinal infection at time of enrollment
Known or suspected toxic megacolon and/or known small bowel ileus
Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy
History of total colectomy or bariatric surgery
Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy
Unable or unwilling to comply with protocol requirements
Expected life expectancy < 6 months
Patients who have CMV >2,000 copies/mL of whole blood or EBV >2,000 copies/mL of whole blood.

Sites / Locations

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fecal Microbiota Transplantation (FMT)

Arm Description

One dose of FMT equal to 30 capsules will be administered on day 1 of a 28 day cycle. Steroids and routine GVHD prophylaxis medications and antibiotics may be administered concurrently with FMT therapy. Participants will be followed for 28 days following completion of the FMT dose or protocol defined outcome. aGVHD will be treated as per standard of care.

Outcomes

Primary Outcome Measures

Number of participants experiencing toxicity

Toxicity is defined as: Any bacterial or fungal infection that can be definitely attributed to FMT. Any grade 3 or more adverse event that occurs during or immediately after receiving the treatment and is definitely attributed to FMT.

Efficacy of FMT therapy in high risk and in steroid refractory GI-aGVHD as defined as number of responses at day 28 (+/- 3 days) post FMT treatment

Response will be determined from the maximum GI-aGVHD stage and grade at day 28 (+/- 3 days) post FMT treatment. Response will be determined by P.I and a second physician. Complete response (CR) is defined as the complete resolution of GI aGVHD symptoms, without secondary GVHD therapy. Partial response (PR) is defined as improvement without complete resolution and without worsening of GI aGVHD, without secondary aGVHD therapy. No response (NR) is defined as the same grade of GVHD, progression, death, or the addition of secondary GVHD therapy. Progression is defined as worsening GI aGVHD.

Secondary Outcome Measures

Non-relapse mortality (NRM) as measured by percentage of participants who die not related to relapse

Relapse as measured by percentage of participants who relapse

Relapse-related mortality as measured by percentage of participants with death related to relapse

Relapse-related mortality as measured by percentage of participants with death related to relapse.

Percentage of participants who develop cGVHD by the end of trial

Overall survival (OS) as measured by percentage of participants who are alive at end of trial

Percentage of patients who discontinue steroids at the end of the study

Percentage of patients who discontinue steroids at the end of the study.

Full Information

NCT ID

NCT04059757

First Posted

August 7, 2019

Last Updated

July 1, 2022

Sponsor

Leland Metheny

1. Study Identification

Unique Protocol Identification Number

NCT04059757

Brief Title

Fecal Microbiota Transplantation For The Treatment Of Gastro-Intestinal Acute GVHD

Official Title

Fecal Microbiota Transplantation For The Treatment Of Gastro-Intestinal Acute Graft Versus Host Disease

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Drugs unavailable

Study Start Date

May 2022 (Anticipated)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Leland Metheny

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Gastro-Intestinal Acute Graft Versus Host Disease (GI-aGVHD) is a complication of allogeneic stem cell transplant which is usually treated with steroids. You are being asked to take part in this study because you have recently been diagnosed with GI-GVHD. The standard of care for GI-aGVHD is steroids. When aGVHD does not respond to steroids it is described as steroid-refractory aGVHD. There is no standard therapy for steroid-refractory GI-aGVHD. This study is a Phase II study. The main goal of a Phase II study is to see the efficacy and what side effects are seen with FMT as a treatment for GVHD. Fecal Microbiota Transplantation (FMT) is the transfer of fecal material from a healthy donor to a patient in order to restore the diversity of the intestinal microbiota. FMT is currently indicated for the treatment of recurrent Clostridium Difficile infection. FMT is considered experimental in this study, meaning it is not approved by the FDA for the treatment of GVHD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastro-Intestinal Acute Graft Versus Host Disease (GI-aGVHD)

Keywords

Graft Versus Host Disease (GVHD)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

The study follows R. Simon's minimax two-stage phase II design with type I error of 0.05 and power of 80%. Ten participants will be enrolled on stage one. If there are 2 or less responses, the trial will be stopped and the treatment will be considered less than 60% effective for this patient population. If there are 3 or more responses, 7 additional patients will be enrolled.

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fecal Microbiota Transplantation (FMT)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Fecal Microbiota Transplantation (FMT)

Intervention Description

1 dose = 30 capsules on day 1 of Fecal Microbiota Transplantation

Primary Outcome Measure Information:

Title

Number of participants experiencing toxicity

Description

Time Frame

up to 6 months from start of treatment

Title

Efficacy of FMT therapy in high risk and in steroid refractory GI-aGVHD as defined as number of responses at day 28 (+/- 3 days) post FMT treatment

Description

Time Frame

28 days (+/- 3 days) post FMT treatment

Secondary Outcome Measure Information:

Title

Non-relapse mortality (NRM) as measured by percentage of participants who die not related to relapse

Description

Non-relapse mortality (NRM) as measured by percentage of participants who die not related to relapse

Time Frame

up to 6 months from start of treatment

Title

Relapse as measured by percentage of participants who relapse

Description

Relapse as measured by percentage of participants who relapse

Time Frame

up to 6 months from start of treatment

Title

Relapse-related mortality as measured by percentage of participants with death related to relapse

Description

Relapse-related mortality as measured by percentage of participants with death related to relapse.

Time Frame

up to 6 months from start of treatment

Title

Percentage of participants who develop cGVHD by the end of trial

Description

Percentage of participants who develop cGVHD by the end of trial

Time Frame

up to 6 months from start of treatment

Title

Overall survival (OS) as measured by percentage of participants who are alive at end of trial

Description

Overall survival (OS) as measured by percentage of participants who are alive at end of trial

Time Frame

up to 6 months from start of treatment

Title

Percentage of patients who discontinue steroids at the end of the study

Description

Percentage of patients who discontinue steroids at the end of the study.

Time Frame

up to 6 months from start of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Maximum Age & Unit of Time

74 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: One of the following diagnosis: High risk aGVHD (either biopsy proven or clinical diagnosed) (see Appendix B & C) as defined by either: Lower gastrointestinal (GI) stage 3+ Hyper-acute GVHD as defined by aGVHD of the GI tract within the first 14 days of transplant AND Subjects with treatment-naive acute GVHD as defined as those who have not received previous systemic treatment for acute GVHD, except for a maximum of 7 days of no less than 1 mg/kg/day of methyl-prednisolone (or equivalent dose of prednisone). OR: Steroid refractory aGVHD of the GI tract (either biopsy proven or clinical diagnosed) as defined by: no response to steroid treatment (minimum daily dose: 2 mg/kg methyl-prednisolone or equivalent) lasting at least 7 days, or progression of at least one grade within the first 72 h of treatment ECOG Performance status < 3 Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source. Patients who are able stop prophylactic antibiotics during the treatment period Subjects must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Active malignancy Patients with any concurrent uncontrolled clinically significant medical condition including active infection, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment. Pregnant or breastfeeding women Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds Patients with any severe gastrointestinal condition other than GI-GVHD. Inability (e.g. dysphagia) to or unwilling to swallow capsules Active gastrointestinal infection at time of enrollment Known or suspected toxic megacolon and/or known small bowel ileus Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy History of total colectomy or bariatric surgery Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy Unable or unwilling to comply with protocol requirements Expected life expectancy < 6 months Patients who have CMV >2,000 copies/mL of whole blood or EBV >2,000 copies/mL of whole blood.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Leland Metheny, MD

Organizational Affiliation

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106-5065

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data that underline or influence the results observed from the study.

IPD Sharing Time Frame

Beginning 3 months and ending 5 years following article publication

IPD Sharing Access Criteria

Investigators who provide a methodologically sound proposal for use of requested data.

Learn more about this trial

Fecal Microbiota Transplantation For The Treatment Of Gastro-Intestinal Acute GVHD

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