Acute Myeloid Leukemia, Allogeneic Hematopoietic Cell Transplantation
Conditions
Keywords
AML, Allo-HCT
Brief summary
This is a randomized, double-blind, placebo-controlled clinical trial of Fecal Microbiota Transplant (FMT) in 2 independent cohorts (60 acute myeloid leukemia patients undergoing intensive chemotherapy and 60 Allo-HCT patients). Participants in each cohort will be randomized in a 2:1 ratio to receive up to 3 treatments of FMT vs. placebo after each exposure to antibacterial antibiotics until 3 months after randomization.
Interventions
BIOLOGICALFecal Microbiota Transplant (FMT)
Oral Capsule
OTHERPlacebo
Oral Capsule
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age≥ 18 years * Cohort A: Patients undergoing intensive induction chemotherapy for acute myeloid leukemia (AML; newly diagnosed or relapsed/refractory). \* Any intensive regimen with planned \ 4 weeks of inpatient stay * Cohort B: Allo-HCT patients \* Any allogeneic transplant regimen with planned GVHD prophylaxis containing generic IV Mycophenolate Mofetil (MMF) and tacrolimus (Tac) * Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control until at least six months post-FMT/placebo * Voluntary written consent signed before performance of any study-related procedure not part of normal medical care
Exclusion criteria
* Planned continuation of antibacterial antibiotics after the first neutrophil recovery (ANC \> 1,000) * Patients who are currently receiving or recently received (within 28 days) other investigational agents. * Pregnant or breast feeding. The FDA has not classified this agent into a specified pregnancy category. Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of FMT in AML Patients and Allo-HCT Recipients - Number of Infections | 4 Months | Number of infections infections until 4 months after the first intervention. Monitored each visit through safety assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Grade II-IV Acute Graft-versus-host Disease (aGVHD II-IV) | Day 180 post-HCT, up to 7 months | Percentage of Participants with Grade II-IV Acute Graft-versus-host Disease (aGVHD II-IV). Monitored each visit through safety assessment. Grade II better, Grade IV worse. |
| Number of BSI of Suspected Gut Origin | 1 week after first FMT treatment | Number of BSI of suspected gut origin. Monitored each visit through safety assessment. |
| FMT Engraftment | 2 Weeks after first FMT treatment | Proportion of Donor Microbiome Fecal Microbiota Transplantation (FMT) Present in Transplant Recipient. Patient and donor samples analyzed with SourceTracker software. |
| Number of Viral Infections | 4 Months after first FMT treatment | Number of Viral Infections. Monitored each visit through safety assessment. |
| Number of Fungal Infections | 4 Months after first FMT treatment | Number of Fungal Infections. Monitored each visit through safety assessment. |
| Number of Bacterial Infections | 4 Months after first FMT treatment | Number of Bacterial Infections. Monitored each visit through safety assessment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AML Patients Undergoing Intensive Chemothera Fecal Microbiota Transplant (FMT): Oral Capsule | 18 |
| AML Patients Undergoing Intensive Chemotherapy Control Placebo: Oral Capsule | 8 |
| Patients Undergoing Allo-HCT Patients Fecal Microbiota Transplant (FMT): Oral Capsule | 49 |
| Patients Undergoing Allo-HCT Patients Control Placebo: Oral Capsule | 25 |
| Total | 100 |
Baseline characteristics
| Characteristic | AML Patients Undergoing Intensive Chemothera | AML Patients Undergoing Intensive Chemotherapy Control | Patients Undergoing Allo-HCT Patients | Patients Undergoing Allo-HCT Patients Control | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 18 Participants | 3 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 7 Participants | 31 Participants | 22 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 7 Participants | 45 Participants | 23 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 15 Participants | 8 Participants | 45 Participants | 23 Participants | 91 Participants |
| Region of Enrollment United States | 18 participants | 8 participants | 49 participants | 25 participants | 100 participants |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 23 Participants | 9 Participants | 46 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 26 Participants | 16 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 8 | 6 / 49 | 3 / 25 |
| other Total, other adverse events | 16 / 18 | 4 / 8 | 22 / 49 | 4 / 25 |
| serious Total, serious adverse events | 16 / 18 | 4 / 8 | 22 / 49 | 4 / 25 |
Outcome results
Primary
Efficacy of FMT in AML Patients and Allo-HCT Recipients - Number of Infections
Number of infections infections until 4 months after the first intervention. Monitored each visit through safety assessment.
Time frame: 4 Months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AML Patients Undergoing Intensive Chemotherapy | Efficacy of FMT in AML Patients and Allo-HCT Recipients - Number of Infections | 1.12 Infections |
| AML Patients Undergoing Intensive Chemotherapy Control | Efficacy of FMT in AML Patients and Allo-HCT Recipients - Number of Infections | 1.50 Infections |
| Patients Undergoing Allo-HCT | Efficacy of FMT in AML Patients and Allo-HCT Recipients - Number of Infections | 0.89 Infections |
| Patients Undergoing Allo-HCT Control | Efficacy of FMT in AML Patients and Allo-HCT Recipients - Number of Infections | 1.09 Infections |
Secondary
FMT Engraftment
Proportion of Donor Microbiome Fecal Microbiota Transplantation (FMT) Present in Transplant Recipient. Patient and donor samples analyzed with SourceTracker software.
Time frame: 2 Weeks after first FMT treatment
Population: Only a subset of patients were evaluable for engraftment analysis. This is because they either didn't provide a sample or their sample didn't meet the quality criteria.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AML Patients Undergoing Intensive Chemotherapy | FMT Engraftment | 0.3192 Proportion of Donor Microbiome FMT |
| AML Patients Undergoing Intensive Chemotherapy Control | FMT Engraftment | 0.1117 Proportion of Donor Microbiome FMT |
Secondary
FMT Engraftment
Proportion of Donor Microbiome Fecal Microbiota Transplantation (FMT) Present in Transplant Recipient. Patient and donor samples analyzed with SourceTracker software.
Time frame: 4 Weeks after first FMT treatment
Population: Only a subset of patients were evaluable for engraftment analysis. This is because they either didn't provide a sample or their sample didn't meet the quality criteria.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AML Patients Undergoing Intensive Chemotherapy | FMT Engraftment | 0.4767 Proportion of Donor Microbiome FMT |
| AML Patients Undergoing Intensive Chemotherapy Control | FMT Engraftment | 0.2626 Proportion of Donor Microbiome FMT |
Secondary
Number of Bacterial Infections
Number of Bacterial Infections. Monitored each visit through safety assessment.
Time frame: 4 Months after first FMT treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AML Patients Undergoing Intensive Chemotherapy | Number of Bacterial Infections | 8 Infections |
| AML Patients Undergoing Intensive Chemotherapy Control | Number of Bacterial Infections | 2 Infections |
| Patients Undergoing Allo-HCT | Number of Bacterial Infections | 10 Infections |
| Patients Undergoing Allo-HCT Control | Number of Bacterial Infections | 2 Infections |
Secondary
Number of BSI of Suspected Gut Origin
Number of BSI of suspected gut origin. Monitored each visit through safety assessment.
Time frame: 1 week after first FMT treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AML Patients Undergoing Intensive Chemotherapy | Number of BSI of Suspected Gut Origin | 0 Bloodstream infections |
| AML Patients Undergoing Intensive Chemotherapy Control | Number of BSI of Suspected Gut Origin | 0 Bloodstream infections |
| Patients Undergoing Allo-HCT | Number of BSI of Suspected Gut Origin | 1 Bloodstream infections |
| Patients Undergoing Allo-HCT Control | Number of BSI of Suspected Gut Origin | 0 Bloodstream infections |
Secondary
Number of Fungal Infections
Number of Fungal Infections. Monitored each visit through safety assessment.
Time frame: 4 Months after first FMT treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AML Patients Undergoing Intensive Chemotherapy | Number of Fungal Infections | 0 Infections |
| AML Patients Undergoing Intensive Chemotherapy Control | Number of Fungal Infections | 0 Infections |
| Patients Undergoing Allo-HCT | Number of Fungal Infections | 1 Infections |
| Patients Undergoing Allo-HCT Control | Number of Fungal Infections | 0 Infections |
Secondary
Number of Viral Infections
Number of Viral Infections. Monitored each visit through safety assessment.
Time frame: 4 Months after first FMT treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AML Patients Undergoing Intensive Chemotherapy | Number of Viral Infections | 2 Infections |
| AML Patients Undergoing Intensive Chemotherapy Control | Number of Viral Infections | 2 Infections |
| Patients Undergoing Allo-HCT | Number of Viral Infections | 13 Infections |
| Patients Undergoing Allo-HCT Control | Number of Viral Infections | 8 Infections |
Secondary
Percentage of Participants With Grade II-IV Acute Graft-versus-host Disease (aGVHD II-IV)
Percentage of Participants with Grade II-IV Acute Graft-versus-host Disease (aGVHD II-IV). Monitored each visit through safety assessment. Grade II better, Grade IV worse.
Time frame: Day 180 post-HCT, up to 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AML Patients Undergoing Intensive Chemotherapy | Percentage of Participants With Grade II-IV Acute Graft-versus-host Disease (aGVHD II-IV) | 29.8 Percentage of participants |
| AML Patients Undergoing Intensive Chemotherapy Control | Percentage of Participants With Grade II-IV Acute Graft-versus-host Disease (aGVHD II-IV) | 8 Percentage of participants |