Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for IBD Caused by IL-10R Gene Deficiency

February 13, 2020 updated by: Xiaowen Zhai, Children's Hospital of Fudan University

Multi-center Clinical Study of Cord Blood Stem Cell Transplantation in The Treatment of Very Early-Onset Inflammatory Bowel Disease Caused by Interleukin-10 Receptor Gene Deficiency

Very early onset inflammatory bowel disease (VEO-IBD) is a special subtype of children's inflammatory bowel disease (IBD). VEO-IBD is mostly caused by single-gene defects and can be cured by allo-hematopoietic stem cell transplantation ( HSCT). Umbilical Cord Blood Transplantation (UCBT) is less reported in these patients.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Very early onset inflammatory bowel disease (VEO-IBD) is a special subtype of children's inflammatory bowel disease (IBD). The clinical characteristics of VEO-IBD patients include early onset, severe diarrhea, severe malnutrition, perianal diseases and repeated infection. Studies have found that VEO-IBD is mostly caused by single-gene defects and can be cured by allo-hematopoietic stem cell transplantation ( HSCT). VEO-IBD is a rare disease. At present, there is no large sample of clinical data for transplantation in these patients. Umbilical Cord Blood Transplantation (UCBT) is less reported. Therefore, many transplantation-related issues need to be further studied, including HSCT indications, transplantation timing, pre-transplantation drug therapy, intestinal protection during transplantation, prevention and treatment of post-transplantation complications and so on. The aim of this study is to investigate the efficacy of UCBT in the treatment of VEO-IBD caused by interleukin-10 receptor (IL10R) gene deficiency, including engraftment rate, disease-free survival rate and overall survival rate, and to evaluate transplant-related mortality and complications. All the selected cases are diagnosed as VEO-IBD with IL10R gene deficiency by enteroscopy, histopathology and gene detection. These patients have no matched sibling donors. Their organs function should be normal. The guardian of the patient has the desire and requirement for UCBT and signs the informed consent before treatment. Cord blood stem cell selection: HLA high-resolution detection of patients before transplantation, searching through cord blood stem cell bank, selecting cord blood stem cells that meet the following criteria: HLA-A, B, C, DRB1 high-resolution (genotype) > 6/8 matching, total number of nuclear cells > 5 x 10^7/kg. Conditioning regimen: fludarabine + busulfan + cyclophosphamide. GVHD prevention: tacrolimus (FK506) or cyclosporine A. Infection prevention: Micafungin/caspofungin before engraftment, voriconazole after engraftment to prevent fungi. Ganciclovir is used from the beginning of conditioning to the infusion of cord blood stem cells, and acyclovir is used to prevent virus infection. SMZ is used to prevent Pneumocystis carinii infection after engraftment until half a year after the withdrawal of immunosuppressive agents.

Procedure/Surgery: Cord Blood Stem Cell Transplantation Unrelated cord blood stem cell selection: HLA high-resolution detection should be performed before transplantation. High-resolution (genotype) matching of HLA-A, B, C and DRB1 should be selected. The total number of nuclear cells should be more than 5*107/kg.

Conditioning regime: fludarabine 30 mg/m2/d for 5 days, busulfan 1 mg/kg for 4 times for 3 days, cyclophosphamide 50 mg/kg for 2 days.

Prevention of GVHD: tacrolimus (FK506) 0.1 mg/kg/day, starting from day 4 before transplantation, taking orally twice on an empty stomach to monitor the blood concentration and keep it at 5-10 ng/ml.

Infection prevention: Micafungin/caspofungin before engraftment, voriconazole after engraftment to prevent fungi. Ganciclovir is used from the beginning of conditioning to the beginning of reinfusion, and acyclovir is used to prevent virus infection until immunosuppressive agents are discontinued after reinfusion. SMZ is used to prevents Pneumocystis carinii infection after engraftment.

Study Type

Observational

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Minhang
      • Shanghai, Minhang, China, 201102
        • Children's Hospital of Fudan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with very early-onset inflammatory bowel disease with interleukin-10 receptor gene deficiency through gastroenterology, pathology and gene diagnosis institutions to improve enteroscopy, histopathology and gene detection.

Description

Inclusion Criteria:

  1. Diagnosis: All selected cases will be diagnosed as very early-onset inflammatory bowel disease with interleukin-10 receptor gene deficiency through gastroenterology, pathology and gene diagnosis institutions to improve enteroscopy, histopathology and gene detection.
  2. The patients have no HLA matched sibling donor.

  3. All organs function normally and meet the following test criteria:

    Liver function ALT, AST < 10 times normal value upper limit, TBIL < 5 times normal value upper limit.

    Renal function BUN and Cr < 1.25 times the upper limit of normal value. ECG and echocardiography showed no cardiac insufficiency.

  4. The legal guardian of the patient has the desire and requirement for the treatment of allogeneic umbilical cord blood stem cell transplantation, and signs the informed consent before treatment. The informed consent should inform all relevant contents of clinical research, patients are willing and abide by the treatment plan, follow-up plan, laboratory examination, etc.

Exclusion Criteria:

  1. There are any contraindications of hematopoietic stem cell transplantation.
  2. There are other serious diseases, such as severe damage to vital organ functions: respiratory failure, cardiac insufficiency, decompensated liver insufficiency, renal insufficiency, uncontrollable infection and so on.
  3. Other drug clinical researchers are under way.
  4. Simultaneously suffering from other serious acute or chronic physical or mental diseases, or abnormal laboratory examinations, may affect patient's life safety and compliance, and affect informed consent, research participation, follow-up or result interpretation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
UCBT-IBD-Case
Very early onset IBD patients who underwent Cord Blood Stem Cell Transplantation.
Procedure: Cord Blood Stem Cell Transplantation
Unrelated cord blood stem cell selection; Reduced intensity conditioning regime; GVHD prevention; Infection prevention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival rate
Time Frame: 3 years after transplantation
Overall survival is defined as the survival status of patients by the end of 3 years after the transplanting, coded as 1 for dead and 0 for survive.
3 years after transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease free survival rate
Time Frame: 3 years after transplantation
Disease free survival is defined as the survival status of patients by the end of the third year after transplantation. Disease free survival is defined as survive without conditions including engraftment failure and death caused by any reasons. The variable is coded as 0 for disease free survive, and 1 for all conditions other than the defined status of "0".
3 years after transplantation
Successful engraftment
Time Frame: 3 years after transplantation
The event of successful engraftment is defined as Neutrophil count ≥ 0.5×10^9/L for continuous 3 days and platelet count ≥ 20×10^9/L for continuous 7 days without transfusion. It is coded as 1.
3 years after transplantation

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The occurrence of adverse events (AE)
Time Frame: 3 years after transplantation
The adverse events (AE) is a composite variable including liver and kidney function damage, nausea, vomiting, arrhythmia and dyspnea. The variable would be coded as 1 if any of these events occurs after transplantation for 3 years while 0 for none . These adverse events would be measured by assessment scale method according to NCI CTC AE v4.0 classification standard.
3 years after transplantation
The occurrence of graft-versus-host disease (GVHD)
Time Frame: 3 years after transplantation
Acute and chronic GVHD is measured and graded as per standardised criteria.
3 years after transplantation
Transplant-related mortality
Time Frame: 3 years after transplantation
Transplant-related mortality (TRM) is defined as the proportion of non primary disease death patients in the total number of cord blood stem cell transplantation patients in the same period within 100 days after transplantation.
3 years after transplantation
The occurrence of transplant-related complications except GVHD
Time Frame: 3 years after transplantation
Transplant-related complications include infections, hepatic venous occlusion disease, hemorrhagic cystitis, capillary leakage syndrome, thrombotic microangiopathy, post-transplantation lymphoproliferative disease, idiopathic pneumonia syndrome and obstructive bronchiolitis, which are diagnosed according to the relevant diagnosis standards of each disease.
3 years after transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Fudan University

Collaborators

The First Affiliated Hospital of Zhengzhou University
Shanghai Children's Hospital
Beijing Children's Hospital
Children's Hospital of Soochow University
Guangzhou Women and Children's Medical Center
Shenzhen Children's Hospital
Children's Hospital of Nanjing Medical University
Wuhan Women and Children's Medical Center

Investigators

  • Study Director: jiang hui, master, Shanghai Children's Hospital
  • Study Director: hu shaoyan, PhD, Children's Hospital of Soochow University
  • Study Director: Qin Maoquan, PHD, Beijing Children's Hospital
  • Study Director: jiang hua, PhD, Guangzhou Women And Children's Medical Center
  • Study Director: liu sixi, master, Shenzhen Children's Hospital
  • Study Director: xiong hao, PhD, Wuhan Women and Children's Medical Center
  • Study Director: fang yongjun, PhD, Children's Hospital of Nanjing Medical University
  • Study Director: wang dao, PhD, The First Affiliated Hospital of Zhengzhou University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2019

Primary Completion (Anticipated)

October 31, 2022

Study Completion (Anticipated)

October 31, 2023

Study Registration Dates

First Submitted

November 12, 2019

First Submitted That Met QC Criteria

November 18, 2019

First Posted (Actual)

November 20, 2019

Study Record Updates

Last Update Posted (Actual)

February 17, 2020

Last Update Submitted That Met QC Criteria

February 13, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CPBMT-IBD-2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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