Clinical trial NCT04170192: Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for IBD Caused by IL-10R Gene Deficiency
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Inflammatory Bowel Diseases
Keywords: Umbilical Cord Blood Stem Cell Transplantation
Inflammatory Bowel Disease
Interleukin 10 Receptor
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
Collaborators: name: Shanghai Children's Hospital
name: Children's Hospital of Soochow University
name: Beijing Children's Hospital
name: Guangzhou Women and Children's Medical Center
name: Shenzhen Children's Hospital
name: Wuhan Women and Children's Medical Center
name: Children's Hospital of Nanjing Medical University
name: The First Affiliated Hospital of Zhengzhou University
First posted: 2019-11-20
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: Overall survival rate
timeFrame: 3 years after transplantation
Secondary outcomes:
measure: Disease free survival rate
timeFrame: 3 years after transplantation
measure: Successful engraftment
timeFrame: 3 years after transplantation
Other outcomes:
measure: The occurrence of adverse events (AE)
timeFrame: 3 years after transplantation
measure: The occurrence of graft-versus-host disease (GVHD)
timeFrame: 3 years after transplantation
measure: Transplant-related mortality
timeFrame: 3 years after transplantation
measure: The occurrence of transplant-related complications except GVHD
timeFrame: 3 years after transplantation
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Minhang
Study officials:
affiliation: Shanghai Children's Hospital
name: Jiang Hui, Master
role: STUDY_DIRECTOR
affiliation: Children's Hospital of Soochow University
name: Hu Shaoyan, PHD
role: STUDY_DIRECTOR
affiliation: Beijing Children's Hospital
name: Qin Maoquan, PHD
role: STUDY_DIRECTOR
affiliation: Guangzhou Women and Children's Medical Center
name: Jiang Hua, PHD
role: STUDY_DIRECTOR
affiliation: Shenzhen Children's Hospital
name: Liu Sixi, Master
role: STUDY_DIRECTOR
affiliation: Wuhan Women and Children's Medical Center
name: Xiong Hao, PHD
role: STUDY_DIRECTOR
affiliation: Children's Hospital of Nanjing Medical University
name: Fang Yongjun, PHD
role: STUDY_DIRECTOR
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Wang Dao, PHD
role: STUDY_DIRECTOR
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