Hematopoietic Stem Cell Transplantation (HSCT)Phase 2NCT02641236
Gut Decontamination In Pediatric Allogeneic Hematopoietic
A Phase 2 study testing Vancomycin-polymyxin B in people with Hematopoietic Stem Cell Transplantation (HSCT) and Acute GVH Disease, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 4 to 30 years
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation (HSCT), Acute GVH Disease
- What is being tested?
- Vancomycin-polymyxin B
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2016to 28 Oct 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: A Randomized Phase 2 Study to Examine the Impact of Gut Decontamination on Intestinal Microbiome Composition in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients
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.
Read the 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.
- Being tested
- Vancomycin-polymyxin B
- Keywords
- Hematopoietic Stem Cell Transplantation (HSCT), Acute GVH Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vancomycin-polymyxin BDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 Weeks post HSCT
Secondary outcomes (5)
Diarrhea Frequency
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.
Measured: Participants were followed 7 days after HSCT.
Median Absolute Cell Numbers of T-, B-, NK- and Dendritic Cell Subsets by Flow Cytometry
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-).
Measured: Performed at the post-transplant time points (1,2,3,6,9,12 months post-transplant)
Incidence of Acute GVHD (Grade 2-4)
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.
Measured: Each stool collection time point after neutrophil engraftment until day +100
Overall Survival Rate at 12 Months (OS12)
OS12 is the proportion of participants alive at 12 months after study entry.
Measured: All participants were followed for 1 years after study entry.
Relapse Free Rate at 12 Months
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.
Measured: Patients were followed for 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study startMar 2016
- Primary completion15 Apr 2021
- Study completion28 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematopoietic Stem Cell Transplantation (HSCT)Studies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Leslie Lehmann, MD, Dana-Farber Cancer Institute
- Investigators
- Leslie Lehmann, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02641236
- Sponsor's protocol ID
- 15-394
- Status last verified
- Sep 2023
- First submitted
- 16 Nov 2015
- Last updated
- 15 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 35239511
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2 Study to Examine the Impact of Gut Decontamination on Intestinal Microbiome Composition in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients
- ClinicalTrials.gov ID
- NCT02641236
- Acronym / sponsor ID
- 15-394
- Keywords
- Hematopoietic Stem Cell Transplantation (HSCT), Acute GVH Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- 15 Apr 2021 (actual)
- Study completion
- 28 Oct 2021 (actual)
- First posted
- 29 Dec 2015 (estimated)
- Results
- Posted 15 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gut Decontamination with vancopoly | Active comparator | Drug: Vancomycin-polymyxin B* 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. |
| 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. |
Who may qualify
- Ages
- 4 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Eligibility Criteria for Patients Undergoing Allogeneic HSCT
- Eligibility Criteria for Healthy Bone Marrow Donors
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vancomycin-polymyxin B | Drug | Gut Decontamination with vancopoly |
Primary outcome
Gut Microbiome Description
Time frame: 2 Weeks post HSCT
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
5 secondary outcomes
Diarrhea Frequency
Time frame: Participants were followed 7 days after HSCT.
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)
Incidence of Acute GVHD (Grade 2-4)
Time frame: Each stool collection time point after neutrophil engraftment until day +100
Overall Survival Rate at 12 Months (OS12)
Time frame: All participants were followed for 1 years after study entry.
Relapse Free Rate at 12 Months
Time frame: Patients were followed for 12 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35239511Severyn 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leslie Lehmann, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vancomycin-polymyxin B in people with Hematopoietic Stem Cell Transplantation (HSCT) and Acute GVH Disease, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gut Microbiome Description (time frame: 2 Weeks post HSCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02641236, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2023.