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Oral Supplementation of 2'-Fucosyllactose in Allogeneic Bone Marrow Transplant Recipients

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ClinicalTrials.gov Identifier: NCT04263597
Recruitment Status : Recruiting
First Posted : February 11, 2020
Last Update Posted : June 9, 2022
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE February 7, 2020
First Posted Date  ICMJE February 11, 2020
Last Update Posted Date June 9, 2022
Actual Study Start Date  ICMJE August 26, 2020
Estimated Primary Completion Date September 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2022)
  • Number of bloodstream infections [ Time Frame: Day+100 after transplant ]
    Number of bloodstream infections in patients on 2FL
  • Number of patients able to take 2FL [ Time Frame: 1 week prior to start of chemotherapy until day+30 after transplant ]
    6 of 10 patients receiving 2FL able to take 80% of their planned doses
Original Primary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • Safety of 2'-fucosyllactose (2FL) [ Time Frame: Day+100 after transplant ]
    More bloodstream infections in 2FL group compared to placebo
  • Tolerability of 2'-fucosyllactose (2FL) [ Time Frame: 1 week prior to start of chemotherapy until day+30 after transplant ]
    6 of 10 patients receiving 2FL able to take 80% of their planned doses
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2022)
  • Relative abundance of fecal Bifidobacteria at day+30 compared to baseline by >/=10% [ Time Frame: Day+30 after transplant ]
    Change in relative abundance of fecal Bifidobacteria at day+30 compared to baseline by >/=10%
  • Relative abundance of fecal Firmicutes and Proteobacteria at day+30 compared to baseline for patients on 2FL [ Time Frame: Day+30 after transplant ]
    Change in relative abundance of fecal Firmicutes and Proteobacteria at day+30 compared to baseline for patients on 2FL
  • Incidence of acute GVHD [ Time Frame: Day+100 after transplant ]
    Incidence of acute GVHD in patients on 2FL
  • Incidence of bloodstream infections [ Time Frame: Day+100 after transplant ]
    Incidence of bloodstream infections in patients on 2FL
Original Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • Relative abundance of fecal Bifidobacteria at day+30 compared to baseline by >/=10% [ Time Frame: Day+30 after transplant ]
    Increase in relative abundance of fecal Bifidobacteria at day+30 compared to baseline by >/=10%
  • Relative abundance of fecal Firmicutes and Proteobacteria at day+30 compared to baseline for patients on 2FL [ Time Frame: Day+30 after transplant ]
    Decrease in relative abundance of fecal Firmicutes and Proteobacteria at day+30 compared to baseline for patients on 2FL
  • Plasma cytokines (IL6, IL8, IL10 and IFNγ) at day+30 in 2FL group compared to placebo [ Time Frame: Day+30 after transplant ]
    Lower plasma cytokines (IL6, IL8, IL10 and IFNγ) at day+30 in 2FL group compared to placebo
  • Plasma reg 3- alpha levels at day+30 in 2FL patients compared to placebo [ Time Frame: Day+30 after transplant ]
    Lower plasma reg 3- alpha levels at day+30 in 2FL patients compared to placebo
  • CD69+ CD8+T-cells at day+30 in 2FL patients compared to placebo. [ Time Frame: day+30 after transplant ]
    Lower CD69+ CD8+T-cells at day+30 in 2FL patients compared to placebo.
  • Fecal human DNA at day+30 in 2FL group compared to placebo [ Time Frame: Day+30 after transplant ]
    Lower fecal human DNA at day+30 in 2FL group compared to placebo
  • Incidence of acute GVHD [ Time Frame: Day+100 after transplant ]
    Incidence of acute GVHD in 2FL group compared to placebo
  • Incidence of bloodstream infections [ Time Frame: Day+100 after transplant ]
    Incidence of bloodstream infections in 2FL group compared to placebo
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oral Supplementation of 2'-Fucosyllactose in Allogeneic Bone Marrow Transplant Recipients
Official Title  ICMJE Oral Supplementation of 2'-Fucosyllactose in Allogeneic Bone Marrow Transplant Recipients to Maintain Intestinal Homeostasis
Brief Summary High dose chemotherapy and radiation used as preparative regimens in patients undergoing an allogeneic hematopoietic stem cell transplant (HSCT) disrupts intestinal homeostasis by damaging the intestinal epithelium and altering the intestinal microbiome. The investigators hypothesize that 2'-fucosyllactose (2FL) supplementation will be safe and tolerable and result in an increase in the relative abundance of intestinal Bifidobacteria. The investigators also hypothesize that 2FL supplementation will lead to reduction of Firmicutes and/or Proteobacteria, and improved intestinal homeostasis at day+30 as measured by lower pro-inflammatory cytokines, reduced levels of T-cell activation, lower markers of intestinal injury (fecal human DNA and plasma reg-3-alpha), increased fecal butyrate levels and ultimately lower incidence of acute GVHD and BSI at day+100.
Detailed Description

This phase I/IIa study is a single center prospective study at Cincinnati Children's Hospital Medical Center (CCHMC).

This study will assess the safety and tolerability of various doses of 2FL. Eligible patients will be allocated to the following arms as determined by age at enrollment:

Arm 1: 0-5 years; Arm 2: 5.1-10 years; Arm 3: >10 years

The investigators will first enroll 5 patients of ages ≥10 years undergoing allogeneic HSCT. 2'-FL will be administered to these patients from day-7 until day+30 after HSCT at the starting dose for the ≥10 years age group. Once safety is determined the investigators will then enroll an additional 5 patients of ages 5-10 years and 5 patients of ages 0-5 years and administer 2'FL at starting doses according to their age group to children from day-7 to day+30 after HSCT. Enrollment in the 2 defined age groups (5-10 years and 0-5 years) will occur independent of each other/in parallel to establish safety. Once safety is established in these patients the investigators will proceed with the 3x3 study design dose finding portion of our study

Three patients will be enrolled in each arm at the starting dose level. Investigators will perform a dose escalation or de-escalation based on rates of dose limiting toxicities.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Eligible patients will be allocated into the following arms as determined by age at enrollment.

Arm 1: 0-5 years; Arm 2: 5.1-10 years; Arm 3: >10 years

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hematopoietic Stem Cell Transplant
Intervention  ICMJE Drug: 2'-fucosyllactose
2FL powder will be provided to participants randomized to receive 2FL in packets. They will be instructed to drink this daily by adding the required amount to food or drink. It may also be mixed in standard feeds or mixed with water and administered by enteral tube, whenever applicable.
Other Name: 2FL supplementation
Study Arms  ICMJE
  • Experimental: 2'-fucosyllactose for ages 0-5 years

    Starting Dose for ages 0-5 years: 2.5 g/day;

    Dose escalation for ages 0-5 years: 5 g/day;

    Dose de-escalation for ages 0-5 years: 1.25 g/day

    Intervention: Drug: 2'-fucosyllactose
  • Experimental: 2'-fucosyllactose for ages 5.1-10 years

    Starting Dose for ages 5.1-10 years: 5 g/day;

    Dose escalation for ages 5.1-10 years: 7.5 g/day;

    Dose de-escalation for ages 5.1-10 years: 2.5 g/day

    Intervention: Drug: 2'-fucosyllactose
  • Experimental: 2'-fucosyllactose for ages >10 years

    Starting dose for ages >10 years: 10 g/day;

    Dose escalation for ages >10 years: 15 g/day;

    Dose de-escalation for ages >10 years: 5 g/day

    Intervention: Drug: 2'-fucosyllactose
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: June 7, 2022)
70
Original Estimated Enrollment  ICMJE
 (submitted: February 7, 2020)
270
Estimated Study Completion Date  ICMJE September 2025
Estimated Primary Completion Date September 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Be scheduled for allogeneic stem cell transplant
  • All ages and underlying diagnoses, preparative regimens, stem cell sources and acute GVHD prophylaxes

Exclusion Criteria:

  • Unable to take anything orally or enterally (i.e. intestinal failure)
  • Actively breastfeeding infants
  • Recent (within the week prior to enrollment) GI infection
  • Patients receiving anti-diarrheal medications such as loperamide
  • Patients who have received probiotics or prebiotics during the previous month
  • Patients who have had any type of gut damage within the past 3 months such as previous bowel perforations, previous episode of Grade 4 neutropenic colitis or typhlitis
  • Patients with inflammatory bowel disease, short bowel syndrome, and patients with a history of bowel resections
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Celeste Dourson (513) 636-7679 Celeste.Dourson@cchmc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04263597
Other Study ID Numbers  ICMJE 2020-0008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Children's Hospital Medical Center, Cincinnati
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pooja Khandelwal, MD Children's Hospital Medical Center, Cincinnati
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date June 2022

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