FMT In High-Risk Acute GVHD After ALLO HCT
FMT In High-Risk Acute GVHD After ALLO HCT
The purpose of this study is to evaluate the effectiveness of Fecal Microbiota Transplant
 (FMT) treatment in high-risk acute graft-versus-host disease (GVHD).

 This research study involves an experimental intervention called FMT.
In this research study, the investigators are evaluating the effectiveness of Fecal
 Microbiota Transplant (FMT) treatment in high-risk acute GVHD. The investigators are
 evaluating the effectiveness of FMT (also known as 'stool transplantation' or 'fecal
 transplant') in being able to transfer gut organisms from a healthy donor to the patient.

 The investigators are also evaluating the ability of this treatment to improve or completely
 resolve the clinical symptoms (diarrhea, abdominal pain, rash, liver inflammation) that can
 occur with acute GVHD.This research study is a Pilot Study, which is the first time
 investigators are examining this intervention for treatment of acute GVHD.

 The FDA (the U.S. Food and Drug Administration) has not approved FMT for this use. The FDA
 has classified human stool as a biological agent and determined that its use in FMT therapy
 should be regulated to ensure patient safety. To use FMT to treat recurrent Clostridium
 difficile infection, the most common indication for FMT, does not require an investigation
 new drug permit. To use FMT for research or to treat any condition other than recurrent
 Clostridium difficile infection requires an investigation new drug permit. An investigation
 new drug permit has been obtained for this study.

 -  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
 graft-versus-host disease (GVHD) is developed. GVHD occurs when donated bone marrow
 cells attack the body with an immune response.

 -  FMT is a process utilizing microbial components which are the good, healthy bacteria
 that would otherwise naturally occur the body. Since may have decreased microbial flora
 diversity after HCT, these microbial components are taken from a stool donor. They are
 extracted from fecal matter (stool) and put into a capsule to ingest.
Inclusion Criteria:

 -  Men or women ≥ 18 years old

 -  Patient has undergone allogeneic hematopoietic cell transplantation from any donor
 (related or unrelated with any degree of HLA matching) and any donor source (bone
 marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or
 disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are
 eligible.

 -  Evidence of myeloid engraftment (eg, absolute neutrophil count ≥ 0.5 × 109/L for 3
 consecutive assessments if ablative therapy was previously used). Use of growth factor
 supplementation is allowed.

 -  Patient must have clinically suspected Grade II to IV aGVHD as per MAGIC criteria.
 Clinical suspicion of aGVHD by the treating physician is sufficient and biopsies are
 not required to pathologically confirm aGVHD. However, in situations where alternative
 diagnoses of drug effects or infection are not adequately ruled out on clinical
 suspicion alone, biopsies are recommended. - Patients must have a diagnosis of
 high-risk acute GVHD, defined as either:

 -- Steroid-refractory GVHD:

 -  Progressive GVHD after at least 3 days of systemic corticosteroids (≥ 1 mg/kg/day
 of prednisone equivalent), OR

 -  No improvement in GVHD after at least 7 days on ≥ 1 mg/kg/day of prednisone
 equivalent or insufficient improvement which warrants the addition of another
 agent, OR

 -  Flare of GVHD symptoms during taper.

 -  High-risk, treatment-naïve GVHD

 -  AA3 risk by Ann Arbor GVHD scoring risk system

 -  Treatment-naïve: less than 3 days of therapy with systemic corticosteroids (≥ 1
 mg/kg/day of prednisone equivalent)

 -  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 large capsules.

 Exclusion Criteria:

 -  Participants who have initiated a new systemic treatment for steroid-refractory GVHD
 (institutional standard or investigational agent) within the 2 weeks prior to first
 dose of FMT. Treatment with FMT is allowed once the time since initiation of newest
 systemic therapy is 2 weeks or longer.

 -  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.

 -  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