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Gut Decontamination In Pediatric Allogeneic Hematopoietic

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ClinicalTrials.gov Identifier: NCT02641236
Recruitment Status : Recruiting
First Posted : December 29, 2015
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Jennifer Whangbo, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE November 16, 2015
First Posted Date  ICMJE December 29, 2015
Last Update Posted Date January 9, 2019
Study Start Date  ICMJE March 2016
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2015)
Gut Microbiome Description [ Time Frame: 2 Weeks post HSCT ]
Shannon diversity index (range: 0-6), measured at 2 weeks post-HSCT.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02641236 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2015)
  • Stool Frequency [ Time Frame: 7 days post-HSCT ]
  • Immune cell profiling: Absolute cell numbers of T-, B-, NK- and dendritic cell subsets by flow cytometry [ Time Frame: Performed prior to day -5 and at the post-transplant time points (1,2,3,6,9,12,18 and 24 months post-transplant) ]
  • Presence of Acute GVHD [ Time Frame: Each stool collection time point after neutrophil engraftment until day +100 ]
  • Overall Survival [ Time Frame: Time from randomization to death due to any cause, or censored at date last known alive. All participants will be followed for 2 years after study entry. ]
  • Progression Free Survival [ Time Frame: Time from randomization to the earlier of progression of malignant disease or death due to any cause. All participants will be followed for 2 years after study entry. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gut Decontamination In Pediatric Allogeneic Hematopoietic
Official Title  ICMJE A Randomized Phase 2 Study to Examine the Impact of Gut Decontamination on Intestinal Microbiome Composition in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients
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.
Detailed Description

This research study is a Phase 2 clinical trial. Phase 2 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.

Pre-clinical studies performed in the 1970's showed that killing all the bacteria in the intestine with oral antibiotics could decrease the risk of acute GVHD following allogeneic HSCT. Based on this observation, many stem cell transplant centers adopted the practice of "gut decontamination" with oral antibiotics as a preventive measure for acute GVHD. There is no standard regimen for gut decontamination between transplant centers, and there are no definitive human studies showing that gut decontamination is beneficial for lowering the risk of acute GVHD.

Recent studies in adult patients undergoing stem cell transplant indicate that the types of bacteria living in the intestine can influence bone marrow transplant outcomes such as survival and development of acute GVHD. Some types of bacteria may be protective against GVHD and others may increase the risk of GVHD. Based on this newer research, it is possible that the practice of gut decontamination ("vancopolys") may not be beneficial for HSCT patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Hematopoietic Stem Cell Transplantation (HSCT)
  • Acute GVH Disease
Intervention  ICMJE Drug: Vancomycin-polymyxin B
Study Arms  ICMJE
  • Active Comparator: Gut Decontamination with vancopoly
    • 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.
    Intervention: Drug: Vancomycin-polymyxin B
  • No Intervention: No Gut Decontamination
    • 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 23, 2015)
28
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2023
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer Whangbo, MD, PhD 617-632-2664 Jennifer_Whangbo@dfci.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02641236
Other Study ID Numbers  ICMJE 15-394
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jennifer Whangbo, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jennifer Whangbo, MD, PhD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP