Fecal Microbiota Transplantation After HSCT
Fecal Microbiota Transplantation After HSCT
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.
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.
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)