Gut Decontamination In Pediatric Allogeneic Hematopoietic

NCT02641236 | Completed Phase 2 Results DMC

• 1 other identifier: 15-394
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is for participants who are undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and are at risk for developing acute graft-versus-host disease (GVHD). GVHD is a complication of HSCT in which immune cells from the donor cause inflammation and injury to tissues and organs of the HSCT recipient. Vancomycin-polymyxin B (commonly called "vancopoly") is an oral antibiotic that is given to people undergoing allogeneic HSCT as a preventive measure for acute GVHD. This research study is studying the effects of vancopoly on the microorganisms living in the intestine during and after stem cell transplantation.

Conditions

Hematopoietic Stem Cell Transplantation (HSCT); Acute GVH Disease

Keywords

Hematopoietic Stem Cell Transplantation (HSCT); Acute GVH Disease

Outcome Measures

Primary Outcomes (1)

• Gut Microbiome Description

  Shannon diversity index (range: 0-6), measured at 2 weeks post stem cell transplant. Shannon diversity is a way to calculate biodiversity in a community, and assumes that all species are represented in a sample and that they are randomly sampled. Shannon Diversity is a measurement sensitive to the loss of rare taxa (34 in the JCI Insight manuscript, Konopinski MK, PeerJ. 2020;8:e9391) and estimates microbial richness (e.g., the number of species) and evenness (e.g., the relative abundance of organisms within a sample). Formula 1: H = -∑\[(pi) \* ln(pi)\], * H: Shannon diversity index (H = 0 indicates that a community has only one species) pi: Proportion of individuals of i-th species in a whole community Formula 2: pi = n / N, * n: individuals of a given type/species * N: total number of individuals in a community

  2 Weeks post HSCT

Secondary Outcomes (5)

• Diarrhea Frequency

  Participants were followed 7 days after HSCT.

• Median Absolute Cell Numbers of T-, B-, NK- and Dendritic Cell Subsets by Flow Cytometry

  Performed at the post-transplant time points (1,2,3,6,9,12 months post-transplant)

• Incidence of Acute GVHD (Grade 2-4)

  Each stool collection time point after neutrophil engraftment until day +100

• Overall Survival Rate at 12 Months (OS12)

  All participants were followed for 1 years after study entry.

• Relapse Free Rate at 12 Months

  Patients were followed for 12 months.

Study Arms (2)

Gut Decontamination with vancopoly

ACTIVE COMPARATOR

* All eligible participants will be randomized to either Arm A: "Gut Decontamination" or Arm B: "No Gut Decontamination". * Participants assigned to this arm will receive non-absorbable, oral vancomycin-polymyxin B as per our institutional standard practice.

Drug: Vancomycin-polymyxin B

No Gut Decontamination

NO INTERVENTION

* All eligible participants will be randomized to either Arm A: "Gut Decontamination" or Arm B: "No Gut Decontamination". * Participants assigned to this arm will not receive oral vancomycin-polymyxin B, but all other HSCT supportive care will be the same as for patients in Arm A.

Interventions

Vancomycin-polymyxin B DRUG

Gut Decontamination with vancopoly

Eligibility Criteria

• Age: 4 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Eligibility Criteria for Patients Undergoing Allogeneic HSCT
• Recipient of 9/10 or 10/10 (HLA-A, -B, -C, -DRB1, -DQB1) matched bone marrow allogeneic hematopoietic stem cell transplantation (HSCT) OR 4/6, 5/6 and 6/6 (HLA-A, -B, -DR) matched cord blood allogeneic HSCT.
• Participants may have underlying malignant or non-malignant hematologic disease, except for primary immunodeficiency, as the indication for their allogeneic HSCT. Patients with immune dysregulation such as familial or secondary hemophagocytic lymphohistiocytosis (HLH) are eligible.
• Participants must may receive either a myeloablative or non-myeloablative(reduced-intensity) conditioning regimen. Anti-thymocyte globulin (ATG) in the conditioning regimen is permitted.
• Graft-versus-host disease (GVHD) prophylaxis with any of the following agents: calcineurin inhibitor, and short-course methotrexate, with or without steroids, mycophenolate mofetil, and sirolimus.
• Age ≥ 4 years old and toilet-trained. Participants must be able to deposit stool samples directly into stool collection containers. Stool specimens from diapers are difficult to obtain and are prone to more sampling error, particularly for loose or liquid stools which are common in the peri-transplant period.
• Lansky/Karnofsky performance status ≥60% (see Appendix A)
• Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document
• Eligibility Criteria for Healthy Bone Marrow Donors
• Healthy individuals, ages ≥ 4 years and toilet-trained, who have been identified by BCH or DFCI providers as 9/10 or 10/10 (HLA-A, -B, -C, -DRB1, -DQB1 matched bone marrow donors for transplantation will also be eligible to participate in this study.

You may not qualify if:

• Patients undergoing allogeneic HSCT for correction of a primary immunodeficiency disorder (e.g. SCID).
• Patients with age ≤ 10 years undergoing HSCT with a matched sibling donor. These patients are at very low risk of acute GVHD and do not receive gut decontamination per our institutional standard practice.
• Participants receiving GVHD prophylaxis with drugs other than calcineurin inhibitors, methotrexate or steroids.agents listed above (e.g. abatacept).
• History of allergic reactions attributed to oral vancomycin or oral polymyxin B.
• Participants undergoing active therapy for immune-mediated or infectious colitis upon admission for allogeneic HSCT.
• Participants receiving antibiotic therapy for treatment of a bacterial infection or bacterial prophylaxis upon admission for allogeneic HSCT. Use of any agent (e.g. sulfamethoxazole/trimethoprim) for prophylaxis of Pneumocystis jirovecii pneumonia is permitted. Concurrent use of anti-fungal and anti-viral therapies is also permitted.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Severyn CJ, Siranosian BA, Kong ST, Moreno A, Li MM, Chen N, Duncan CN, Margossian SP, Lehmann LE, Sun S, Andermann TM, Birbrayer O, Silverstein S, Reynolds CG, Kim S, Banaei N, Ritz J, Fodor AA, London WB, Bhatt AS, Whangbo JS. Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation. JCI Insight. 2022 Apr 8;7(7):e154344. doi: 10.1172/jci.insight.154344.

  PMID: 35239511 DERIVED

Results Point of Contact

• Title: Dr. Leslie Lehmann
• Organization: Dana-Farber Cancer Institute

Leslie_Lehmann@DFCI.HARVARD.EDU

617-632-4882

Study Officials

• Leslie Lehmann, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 16, 2015
• First Posted: December 29, 2015
• Study Start: March 1, 2016
• Primary Completion: April 15, 2021
• Study Completion: October 28, 2021
• Last Updated: September 15, 2023
• Results First Posted: September 15, 2023

Record last verified: 2023-09

Locations

US (2)