Allogeneic Hematopoietic Cell Transplantation (HCT)
Conditions
Keywords
Allogeneic Hematopoietic Cell Transplantation (HCT)
Brief summary
This research study is studying the role fecal microbiota transplantation may play in post-Hematopoietic Cell Transplantation (HCT) recipients
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
Interventions
DRUGFMT
FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur in the body.
DRUGPlacebo
a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.
Sponsors
Zachariah Michael DeFilipp
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Number of Participants With Infection at 100 Days | 100 Days | — |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
There were 2 participants who withdrew from the trial prior to randomization thus not evaluable.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3 |
| 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. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | FMT Capsules | Placebo Capsules | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 1 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 |
Outcome results
Primary
The Proportion of Patients Who Achieve Gut Microbiome Diversity at One Month Following the Final Post-HCT FMT
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
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.
Secondary
Graft Versus Host Disease(GVHD)/ Relapse Free Survival (GRFS)
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FMT Capsules | Graft Versus Host Disease(GVHD)/ Relapse Free Survival (GRFS) | 0 Participants |
| Placebo Capsules | Graft Versus Host Disease(GVHD)/ Relapse Free Survival (GRFS) | 2 Participants |
Secondary
Number of Participants With Acute Graft-Versus-Host-Disease (GvHD)
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FMT Capsules | Number of Participants With Acute Graft-Versus-Host-Disease (GvHD) | 2 Participants |
| Placebo Capsules | Number of Participants With Acute Graft-Versus-Host-Disease (GvHD) | 0 Participants |
Secondary
Number of Participants With Infection at 100 Days
Time frame: 100 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FMT Capsules | Number of Participants With Infection at 100 Days | 2 Participants |
| Placebo Capsules | Number of Participants With Infection at 100 Days | 0 Participants |
Secondary
Number of Participants With Non-relapse-mortality
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FMT Capsules | Number of Participants With Non-relapse-mortality | at 6 months | 1 Participants |
| FMT Capsules | Number of Participants With Non-relapse-mortality | at 12 months (cumulative) | 2 Participants |
| Placebo Capsules | Number of Participants With Non-relapse-mortality | at 6 months | 0 Participants |
| Placebo Capsules | Number of Participants With Non-relapse-mortality | at 12 months (cumulative) | 0 Participants |
Secondary
Number of Participants With Progression Free Survival at 12 Months Post-treatment
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FMT Capsules | Number of Participants With Progression Free Survival at 12 Months Post-treatment | 1 Participants |
| Placebo Capsules | Number of Participants With Progression Free Survival at 12 Months Post-treatment | 1 Participants |
Secondary
Overall Survival
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FMT Capsules | Overall Survival | 1 Participants |
| Placebo Capsules | Overall Survival | 2 Participants |