Fecal Microbiota Transplantation for the Treatment of Severe Acute Gut Graft-Versus-Host Disease

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial studies the side effects of using an investigational procedure (fecal microbiota transplantation [FMT]) in treating patients with severe acute gut graft-versus-host-disease. The purpose of a fecal microbiota transplantation is to use feces from a healthy human donor to replace the abnormal gut bacteria in the recipient. One of the side effects of a stem cell transplant is the development of graft-versus-host disease (GvHD) in several organs including gut. GvHD is caused by the donated bone marrow or peripheral blood cells recognizing the recipient's body as foreign and attacking it. Acute gut GvHD is one of the leading causes of death after transplant. Recently, studies have shown that patients with reduced intestinal bacterial diversity in their stool during acute gut GvHD have higher overall mortality rates. The information learned from this study may offer FMT as a promising therapy for the treatment of severe acute gut graft-versus-host-disease.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jonsson Comprehensive Cancer Center
• Collaborator: National Cancer Institute (NCI)

Criteria

Inclusion Criteria:

• Subjects who received an allogenic hematopoietic stem cell transplantation (HSCT)

• Acute GvHD defined as experiencing GvHD symptoms starting prior to day +100 after HSCT

• Gut GvHD defined as subjects experiencing GvHD symptoms consistent with stage 3 or stage 4 by Center for International Blood and Marrow Transplant Research (CIBMTR) staging:

• Stage 3 acute gut GvHD subjects having 1500-1999 mL stool per day

• Stage 4 subjects having greater than 2 liters of stool per day and/or severe abdominal cramping, bleeding or ileus

• Steroid-refractory acute gut GVHD defined as progression of symptoms after 3 days of systemic steroids (> 1 mg/kg/day methylprednisolone) or steroid-resistant acute gut GvHD defined stable symptoms after 5 days of systemic steroids (> 1 mg/kg/day methylprednisolone)

• Able to swallow capsules without aspiration or dysphagia

• Ability to understand the written informed consent and the willingness to sign the consent and accept the risk of receiving unrelated donor stool

Exclusion Criteria:

• Absolute neutrophil count < 500 cells/uL

• Presence of recurrent Clostridium difficile infection

• Presence of ileus or toxic megacolon

• History of multi-drug resistant stool pathogen

• History of inflammatory bowel disease (i.e Crohn's disease or ulcerative colitis)

• Uncontrolled and active systemic infection from bacteria, virus or fungus

• Human immunodeficiency virus (HIV)-positive subjects

• Quantifiable cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) evaluated by polymerase chain reaction (PCR) after hematopoietic stem cell transplantation (HSCT) and after neutrophil engraftment defined as absolute neutrophil count (ANC) > 500 cells/uL

• Hemodynamically unstable

• Active gastrointestinal bleed

• Pregnant and/or breastfeeding women

• Dysphagia due to oropharyngeal, esophageal, functional, neuromuscular (e.g. stroke, multiple sclerosis, amyotrophic lateral sclerosis [ALS]) or subject shows evidence of dysphagia when the 'safety test' capsule is administered

• Delayed gastric emptying syndrome

• Known chronic aspiration

• Subjects with a history of significant allergy to foods

• Subjects with allergies to sodium chloride, glycerol, theobroma oil, hide bovine gelatin, sodium lauryl sulfate, colorants Federal Food, Drug, and Cosmetic Act (FD&C), or titanium dioxide, all ingredients generally recognized as safe (GRAS)

• History of previous gastrointestinal surgery

• Subjects who are receiving other investigational agents for treatment of gut GvHD