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

NCT ID: NCT04170192

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-12-01
• Study Completion Date: 2023-10-31

Brief Summary

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.

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.

Conditions

Inflammatory Bowel Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

UCBT-IBD-Case

Very early onset IBD patients who underwent Cord Blood Stem Cell Transplantation.

Cord Blood Stem Cell Transplantation

Intervention Type: PROCEDURE

Unrelated cord blood stem cell selection; Reduced intensity conditioning regime; GVHD prevention; Infection prevention.

Interventions

Cord Blood Stem Cell Transplantation

Unrelated cord blood stem cell selection; Reduced intensity conditioning regime; GVHD prevention; Infection prevention.

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Children's Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital of Soochow University

OTHER

Sponsor Role: collaborator

Beijing Children's Hospital

OTHER

Sponsor Role: collaborator

Guangzhou Women and Children's Medical Center

OTHER

Sponsor Role: collaborator

Shenzhen Children's Hospital

OTHER_GOV

Sponsor Role: collaborator

Wuhan Women and Children's Medical Center

OTHER

Sponsor Role: collaborator

Children's Hospital of Nanjing Medical University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: collaborator

Children's Hospital of Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xiaowen Zhai

vice president

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jiang Hui, Master

Role: STUDY_DIRECTOR

Shanghai Children's Hospital

Hu Shaoyan, PHD

Role: STUDY_DIRECTOR

Children's Hospital of Soochow University

Qin Maoquan, PHD

Role: STUDY_DIRECTOR

Beijing Children's Hospital

Jiang Hua, PHD

Role: STUDY_DIRECTOR

Guangzhou Women and Children's Medical Center

Liu Sixi, Master

Role: STUDY_DIRECTOR

Shenzhen Children's Hospital

Xiong Hao, PHD

Role: STUDY_DIRECTOR

Wuhan Women and Children's Medical Center

Fang Yongjun, PHD

Role: STUDY_DIRECTOR

Children's Hospital of Nanjing Medical University

Wang Dao, PHD

Role: STUDY_DIRECTOR

The First Affiliated Hospital of Zhengzhou University

Locations

Children's Hospital of Fudan University

Shanghai, Minhang, China

Countries

China

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Other Identifiers

CPBMT-IBD-2019

Identifier Type: -

Identifier Source: org_study_id