- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02641236
Gut Decontamination In Pediatric Allogeneic Hematopoietic
A Randomized Phase 2 Study to Examine the Impact of Gut Decontamination on Intestinal Microbiome Composition in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients
Study Overview
Status
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02115
- Boston Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Gut Decontamination with vancopoly
|
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No Intervention: No Gut Decontamination
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gut Microbiome Description
Time Frame: 2 Weeks post HSCT
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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)],
|
2 Weeks post HSCT
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Diarrhea Frequency
Time Frame: Participants were followed 7 days after HSCT.
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The number of daily bowel movements during the first 7 days post-HSCT is charted by floor nurses and/or clinical assistants and will be obtained from within each patient's electronic medical record in PowerChart.
Diarrhea frequency is defined the proportion of participants who had greater than 3 bowel movements per day.
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Participants were followed 7 days after HSCT.
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Median Absolute Cell Numbers of T-, B-, NK- and Dendritic Cell Subsets by Flow Cytometry
Time Frame: Performed at the post-transplant time points (1,2,3,6,9,12 months post-transplant)
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CD4+ Tregs were defined as CD3+CD4+CD25med-hiCD127lo, CD4+; Tcon as CD3+CD4+CD25neg-lo CD127med-hi, B cells as CD19+, cytotoxic T cells as CD8+, and natural killer cells as CD56+CD3-.
Within CD4+ Tregs and CD4+ Tcon, subsets were defined as follows: naive T cells (CD45RO-CD62L+), central memory (CD45RO+CD62L+), and effector memory (CD45RO+CD62L-).
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Performed at the post-transplant time points (1,2,3,6,9,12 months post-transplant)
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Incidence of Acute GVHD (Grade 2-4)
Time Frame: Each stool collection time point after neutrophil engraftment until day +100
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Grade 2 acute GVHD was defined as skin stage 3 or GI stage 1 or liver stage 1.
Skin stage 3 was defined as maculopapular rash >50% of body surface or generalized erythroderma; GI stage 1 was defined as adults: 500 - 1000 mL/day, children: 10 - 19.9 mL/kg/day or nausea, anorexia or vomiting with biopsy (EGD) confirmation of upper GI GVHD; liver stage 1 was defined as bilirubin 2.1-3 mg/dL.
Grade 3 acute GVHD was defined as GI stage 2-4 or liver stage 2-3.
GI stage 2-4 was defined as >1001 mL/day (adults), >30 ml/kg/day(children) or large volume stool with severe abdominal pain with our whiteout ileus or stool with frank blook or melena; liver stage 2-3 was defined as bilirubin 3.1-15mg/dL.
Grade 4 acute GVHD was defined as skin stage 4 or liver stage 4. Skin stage 4 was defined as generalized erythroderma with bullous formation and desquamation; liver stage 4 was defined as bilirubin > 15mg/dL.
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Each stool collection time point after neutrophil engraftment until day +100
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Overall Survival Rate at 12 Months (OS12)
Time Frame: All participants were followed for 1 years after study entry.
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OS12 is the proportion of participants alive at 12 months after study entry.
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All participants were followed for 1 years after study entry.
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Relapse Free Rate at 12 Months
Time Frame: Patients were followed for 12 months.
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Relapse free rate at 12 months was defined as the proportion of patients surviving without any signs or symptoms of that cancer after 12 months.
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Patients were followed for 12 months.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Leslie Lehmann, MD, Dana-Farber Cancer Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 15-394
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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