Clinical trial NCT02733744: Fecal Microbiota Transplantation After HSCT
Official title: A Pilot Study to Determine the Feasibility of Fecal MicrobiotaTransplantation (FMT) in Hematopoietic Stem Cell Transplantation (HSCT) Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Bone Marrow Transplantation
Keywords: Stem cell transplant
fecal microbiota transplantation
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2016-04-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is studying an intervention called fecal microbiota transplantation (FMT). Patients who are scheduled to undergo Hematopoietic Stem Cell Transplantation are invited to take part in this clinical trial to undergo empiric FMT soon after hematopoietic engraftment. The primary endpoint will be to assess the feasibility of FMT in this population and to assess safety.

Detailed description: The microbiome (spectrum of bacteria in a patient's gut) is thought to play a role in helping to shape one's immune system given its direct contact with normal cells in our intestine. Recent studies have suggested that a microbiome with very few bacteria (low diversity) seems to be bad for health and a high-diversity microbiome (many different species) appears to be good. This appears to be true even for patients after HSCT where low diversity microbiome status has correlated with infections, GVHD and overall survival.

Fecal microbiota transplantation (FMT) is routinely performed for an infection caused by Clostridium difficile but is not yet approved by the FDA as a treatment for any disease. FMT restores a high diversity microbiome. It is hoped that through FMT, overall outcomes after HSCT can potentially be improved.

FMT will be performed in the first 3 weeks after recovery of white blood cells after HSCT. The source of FMT will be from healthy 3rd party donors. FMT will be performed through the ingestion of 30 capsules over 2 consecutive days.

Eligibility criteria: Inclusion Criteria:

* Men or women ≥ 18 and ≤ 65 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 Consensus Criteria (Bacigalupo 2009) as well as the combination of fludarabine with melphalan (100-140 mg/mg2)
* Any Graft-vs-Host disease (GVHD) prophylaxis regimen is allowed.
* Eastern Cooperative Oncology Group (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
    * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Alkaline Phosphatase \< 5 x Upper Limit of Institutional Normal Range (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) ≥ 40millileters/min/1.73m2.
  * Pulmonary: Diffusing lung capacity for carbon monoxide (DLCO) (corrected for hemoglobin), Forced expiratory volume in 1 second (FEV1) and Forced vital capacity (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. 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 oral medications.

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.
* Patients with history of primary idiopathic myelofibrosis or any severe marrow fibrosis.
* Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.
* Delayed gastric emptying syndrome
* Known chronic aspiration
* Patients 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)

Primary outcomes:
measure: Feasibility measured by number of participants able to ingest 15 FMT capsules over a 2-day period
timeFrame: 2 days
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 2 years
measure: Overall Survival
timeFrame: 2 years
measure: Cumulative Incidence Of aGVHD
timeFrame: 2 years
measure: Non-Relapse Mortality Rate
timeFrame: 2 years
measure: Number of participants with treatment-related adverse events
timeFrame: 1 year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts general Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Yi-Bin Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: DeFilipp Z, Peled JU, Li S, Mahabamunuge J, Dagher Z, Slingerland AE, Del Rio C, Valles B, Kempner ME, Smith M, Brown J, Dey BR, El-Jawahri A, McAfee SL, Spitzer TR, Ballen KK, Sung AD, Dalton TE, Messina JA, Dettmer K, Liebisch G, Oefner P, Taur Y, Pamer EG, Holler E, Mansour MK, van den Brink MRM, Hohmann E, Jenq RR, Chen YB. Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. Blood Adv. 2018 Apr 10;2(7):745-753. doi: 10.1182/bloodadvances.2018017731.