Trial Outcomes & Findings for Fecal Microbiota Transplantation (FMT) in Recipients After Allogeneic Hematopoietic Cell Transplantation (HCT) (NCT NCT03720392)

NCT ID: NCT03720392

Last Updated: 2021-12-01

Results Overview

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).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: 1 Month
• Results posted on: 2021-12-01

Participant Flow

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

Participant milestones

Measure	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, FMT: FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.	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, Placebo: a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Overall Study STARTED	3	3
Overall Study COMPLETED	3	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	FMT Capsules n=3 Participants * 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.	Placebo Capsules n=3 Participants * 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 n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 Month

Population: 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.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	FMT Capsules n=3 Participants * 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.	Placebo Capsules n=3 Participants * 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.
Number of Participants With Acute Graft-Versus-Host-Disease (GvHD)	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	FMT Capsules n=3 Participants * 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.	Placebo Capsules n=3 Participants * 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.
Number of Participants With Non-relapse-mortality at 6 months	1 Participants	0 Participants
Number of Participants With Non-relapse-mortality at 12 months (cumulative)	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 100 Days

Outcome measures

Measure	FMT Capsules n=3 Participants * 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.	Placebo Capsules n=3 Participants * 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.
Number of Participants With Infection at 100 Days	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	FMT Capsules n=3 Participants * 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.	Placebo Capsules n=3 Participants * 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.
Number of Participants With Progression Free Survival at 12 Months Post-treatment	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	FMT Capsules n=3 Participants * 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.	Placebo Capsules n=3 Participants * 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.
Overall Survival	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	FMT Capsules n=3 Participants * 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.	Placebo Capsules n=3 Participants * 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.
Graft Versus Host Disease(GVHD)/ Relapse Free Survival (GRFS)	0 Participants	2 Participants

Adverse Events

FMT Capsules

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

Placebo Capsules

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Measure	FMT Capsules n=3 participants at risk * 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.	Placebo Capsules n=3 participants at risk * 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.
Infections and infestations Sepsis	33.3% 1/3 • Number of events 1 • 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.	0.00% 0/3 • 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.

Other adverse events

Measure	FMT Capsules n=3 participants at risk * 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.	Placebo Capsules n=3 participants at risk * 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.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • 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.	33.3% 1/3 • 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.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • 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.	0.00% 0/3 • 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.
Blood and lymphatic system disorders Febrile neutropenia	66.7% 2/3 • 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.	0.00% 0/3 • 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.
Vascular disorders Hypertension	33.3% 1/3 • 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.	33.3% 1/3 • 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.
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • 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.	0.00% 0/3 • 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.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • 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.	0.00% 0/3 • 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.
Gastrointestinal disorders Nausea	66.7% 2/3 • 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.	0.00% 0/3 • 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.
Investigations Neutrophil count decreased	66.7% 2/3 • 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.	33.3% 1/3 • 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.
Investigations Platelet count decreased	66.7% 2/3 • 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.	100.0% 3/3 • 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.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/3 • 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.	33.3% 1/3 • 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.

Additional Information

Zachariah DeFilipp, MD

Massachusetts General Hospital

Phone: 617-643-3944

Email: ZDEFILIPP@MGH.HARVARD.EDU

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place