Fecal Microbiota Transplantation (FMT) in Recipients After Allogeneic Hematopoietic Cell Transplantation (HCT)

Zachariah Michael DeFilipp

Status and phase: Terminated; Phase 2

Conditions: Allogeneic Hematopoietic Cell Transplantation (HCT)

Treatments: Drug: FMT; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03720392

18-293

Details and patient eligibility

About

This research study is studying the role fecal microbiota transplantation may play in post-Hematopoietic Cell Transplantation (HCT) recipients

Full 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

Enrollment: 8 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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8 participants in 2 patient groups, including a placebo group

FMT Capsules

Experimental group

Description:

* 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,

Treatment:

Drug: FMT

Placebo Capsules

Placebo Comparator group

Description:

* 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,

Treatment:

Drug: Placebo