Fecal Microbiota Transplantation (FMT) in Recipients After Allogeneic Hematopoietic Cell Transplantation (HCT)

• Sponsor: Zachariah Michael DeFilipp (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03720392
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This research study is studying the role fecal microbiota transplantation may play in post-Hematopoietic Cell Transplantation (HCT) recipients

Condition or Disease	Intervention/Treatment	Phase
Allogeneic Hematopoietic Cell Transplantation (HCT)	Drug: FMT; Drug: Placebo	Phase 2

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved FMT for this use.

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 a person develop a disease called graft-versus-host disease (GVHD). GVHD occurs when donated bone marrow cells attack the body with an immune response. Researchers believe that more microbial flora diversity in the gut is linked to a lower risk of developing GVHD.

FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body. Since the participant may have decreased microbial flora diversity after HCT, these microbial components are taken from a 3rd party donor. They are extracted from fecal matter (stool) and put into a capsule which the participant then ingest.

Researchers believe that FMT administration may play a role in restoring higher microbial flora diversity in the gut. Therefore, FMT administration may play a role in decreasing the likelihood of developing GVHD.

In this research study, the investigators are...

• Examining the microbial flora diversity of your gut after FMT administration

• Looking for incidence rate of GVHD and other post-HCT complications

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Fecal Microbiota Transplantation (FMT) in Recipients After Allogeneic Hematopoietic Cell Transplantation (HCT)
• Actual Study Start Date: Jan 15, 2019
• Actual Primary Completion Date: May 28, 2020
• Actual Study Completion Date: May 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FMT Capsules Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days,	Drug: FMT; FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.
Placebo Comparator: Placebo Capsules Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days,	Drug: Placebo; a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.

Outcome Measures

Primary Outcome Measures

1. The Proportion of Patients Who Achieve Gut Microbiome Diversity at One Month Following the Final Post-HCT FMT [1 Month]

   Gut microbiome diversity will be assessed using urinary 3-indoxyl sulfate (3-IS) levels, with 35 umol/mmol creatinine as the cutoff (≥ 35: diverse; < 35: not diverse).

Secondary Outcome Measures

1. Number of Participants With Acute Graft-Versus-Host-Disease (GvHD) [6 months]

   The cumulative incidence of overall grades II-IV and grades III-IV acute GVHD will be assessed through six months after last dose of FMT or placebo. Acute GVHD will be assessed using the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria.

2. Number of Participants With Non-relapse-mortality [6 Months and 12 months]

   Non-relapse mortality (NRM) is defined as the time from first dose of FMT or placebo to death without relapse or progression or underlying disease.

3. Number of Participants With Infection at 100 Days [100 Days]

4. Number of Participants With Progression Free Survival at 12 Months Post-treatment [12 Months]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression-Free Survival (PFS) is defined as the time from first dose of FMT or placebo to the earlier of underlying disease progression or death due to any cause. PFS was assessed at 12 months for all participants.

5. Overall Survival [12 Months]

   Overall survival is measured as the amount of time from the first dose of Fecal Microbiota Transplantation (FMT) or placebo, that participants in this study are still alive. Overall survival is reported as number of participants alive at 12 months.

6. Graft Versus Host Disease(GVHD)/ Relapse Free Survival (GRFS) [12 Months]

   GVHD-Free/Relapse-Free Survival (GRFS) is measured as the amount of time from the first dose of Fecal Microbiota Transplantation (FMT) or placebo, that participants in this study are not diagnosed with GVHD, disease progression, or relapse. GRFS is reported as number of patients without GVHD, disease progression, or relapse at 12 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women ≥ 18 and ≤ 80 years old

• Patients designated to undergo myeloablative or intermediate intensity allogeneic peripheral blood or bone marrow hematopoietic cell transplantation. Consent will be obtained prior to admission for HSCT. Patients receiving any donor source of stem cells are eligible. Eligible conditioning regimens are those defined as myeloablative by the ASBMT Consensus Criteria (Bacigalupo 2009) as well as the combination of fludarabine with melphalan (100-140 mg/mg2)

• Any GVHD prophylaxis regimen is allowed.

• ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A)

• Patients with adequate physical function as measured by

• Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction >25%

• Hepatic:

• Bilirubin ≤ 2.5 mg/dL, except for patients with Gilbert's syndrome or hemolysis

• ALT, AST, and Alkaline Phosphatase < 5 x ULN

• Renal: Serum creatinine within normal range, or if serum creatinine is outside normal range, then renal function (measured or estimated creatinine clearance or GFR) ≥ 40mL/min/1.73m2

• Pulmonary: DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted

• 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. Women of childbearing potential will have a urine pregnancy test, which must be negative, on Study Day 1, prior to receiving FMT. 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:

• Prior allogeneic hematopoietic stem cell transplantation. (Patients may have received a prior autologous hematopoietic stem cell transplant.)

• Participants who are receiving any other investigational agents.

• 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.

• Patients with active or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.

• Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02214

Sponsors and Collaborators

• Zachariah Michael DeFilipp

Investigators

• Principal Investigator: Zachariah DeFilipp, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 11, 2019

More Information

Publications

None provided.

• Responsible Party: Zachariah Michael DeFilipp, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03720392
• Other Study ID Numbers: 18-293
• First Posted: Oct 25, 2018
• Last Update Posted: Dec 1, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Zachariah Michael DeFilipp, Principal Investigator, Massachusetts General Hospital: Allogeneic Hematopoietic Cell Transplantation (HCT)

Study Results

Participant Flow

Pre-assignment Detail	There were 2 participants who withdrew from the trial prior to randomization thus not evaluable.

Arm/Group Title	FMT Capsules	Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Period Title: Overall Study
STARTED	3	3
COMPLETED	3	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	FMT Capsules	Placebo Capsules	Total
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.	Total of all reporting groups
Overall Participants	3	3	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	1 33.3%	3 50%
>=65 years	1 33.3%	2 66.7%	3 50%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 33.3%	2 33.3%
Male	2 66.7%	2 66.7%	4 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	3 100%	3 100%	6 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Patients Who Achieve Gut Microbiome Diversity at One Month Following the Final Post-HCT FMT
Description	Gut microbiome diversity will be assessed using urinary 3-indoxyl sulfate (3-IS) levels, with 35 umol/mmol creatinine as the cutoff (≥ 35: diverse; < 35: not diverse).
Time Frame	1 Month

Outcome Measure Data

Analysis Population Description

No analyses for this primary outcome were performed because the study was terminated after only 6 treated patients and there were only a few samples collected.

Arm/Group Title	FMT Capsules	Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Measure Participants	0	0

2. Secondary Outcome

Title	Number of Participants With Acute Graft-Versus-Host-Disease (GvHD)
Description	The cumulative incidence of overall grades II-IV and grades III-IV acute GVHD will be assessed through six months after last dose of FMT or placebo. Acute GVHD will be assessed using the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FMT Capsules	Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Measure Participants	3	3
Count of Participants [Participants]	2 66.7%	0 0%

3. Secondary Outcome

Title	Number of Participants With Non-relapse-mortality
Description	Non-relapse mortality (NRM) is defined as the time from first dose of FMT or placebo to death without relapse or progression or underlying disease.
Time Frame	6 Months and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FMT Capsules	Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Measure Participants	3	3
at 6 months	1 33.3%	0 0%
at 12 months (cumulative)	2 66.7%	0 0%

4. Secondary Outcome

Title	Number of Participants With Infection at 100 Days
Time Frame	100 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FMT Capsules	Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Measure Participants	3	3
Count of Participants [Participants]	2 66.7%	0 0%

5. Secondary Outcome

Title	Number of Participants With Progression Free Survival at 12 Months Post-treatment
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression-Free Survival (PFS) is defined as the time from first dose of FMT or placebo to the earlier of underlying disease progression or death due to any cause. PFS was assessed at 12 months for all participants.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FMT Capsules	Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Measure Participants	3	3
Count of Participants [Participants]	1 33.3%	1 33.3%

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival is measured as the amount of time from the first dose of Fecal Microbiota Transplantation (FMT) or placebo, that participants in this study are still alive. Overall survival is reported as number of participants alive at 12 months.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FMT Capsules	Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Measure Participants	3	3
Count of Participants [Participants]	1 33.3%	2 66.7%

7. Secondary Outcome

Title	Graft Versus Host Disease(GVHD)/ Relapse Free Survival (GRFS)
Description	GVHD-Free/Relapse-Free Survival (GRFS) is measured as the amount of time from the first dose of Fecal Microbiota Transplantation (FMT) or placebo, that participants in this study are not diagnosed with GVHD, disease progression, or relapse. GRFS is reported as number of patients without GVHD, disease progression, or relapse at 12 months.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FMT Capsules	Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Measure Participants	3	3
Count of Participants [Participants]	0 0%	2 66.7%

Adverse Events

Time Frame	Adverse event data collection time frame was approximately 13 months, starting 1 week after allogeneic hematopoietic cell transplantation (HCT) until 12 months after the second fecal microbiota transplantation (FMT) or placebo administration.
Arm/Group Title	FMT Capsules		Placebo Capsules
Arm/Group Description	Two doses of FMT: one standard dose starting within four (4) days from the start of the conditioning regimen prior to HCT and one non-standard dose starting within 4 weeks after engraftment after HCT. A standard dose of oral FMT is 15 capsules per day for two consecutive days, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.		Two doses of placebo, instead of FMT: one starting within four (4) days from the start of the conditioning regimen prior to HCT and the second one starting within 4 weeks after engraftment after HCT. A standard dose of oral Placebo is 15 capsules per day for two consecutive days, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
All Cause Mortality
	FMT Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		1/3 (33.3%)
Serious Adverse Events
	FMT Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/3 (0%)
Infections and infestations
Sepsis	1/3 (33.3%)	1	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	FMT Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	2/3 (66.7%)		0/3 (0%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		1/3 (33.3%)
Diarrhea	1/3 (33.3%)		0/3 (0%)
Nausea	2/3 (66.7%)		0/3 (0%)
Investigations
Neutrophil count decreased	2/3 (66.7%)		1/3 (33.3%)
Platelet count decreased	2/3 (66.7%)		3/3 (100%)
Metabolism and nutrition disorders
Hyponatremia	1/3 (33.3%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/3 (33.3%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Skin ulceration	0/3 (0%)		1/3 (33.3%)
Vascular disorders
Hypertension	1/3 (33.3%)		1/3 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.