Clinical trial NCT04172181: Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID
Official title: Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for Severe Combined Immunodeficiency Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Severe Combined Immunodeficiency Disease
Keywords: cord blood stem cell transplantation
severe combined immunodeficiency disease
primary immunodeficiency
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: 2019-11-21
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 were diagnosed as severe combined immunodeficiency disease by immunological function and genetic diagnosis center.

Brief summary: Severe combined immunodeficiency (SCID) is a rare disease caused by a group of genetic disorders that leads to early death from recurrent infections in affected children.The only curative therapy for SCID is allogeneic hematopoietic stem cell transplantation.Unrelated umbilical cord blood(UCB) is increasingly used as an alternative to bone marrow.

Detailed description: Severe combined immunodeficiency (SCID) is a rare disease caused by a group of genetic disorders that leads to early death from recurrent infections in affected children.The only curative therapy for SCID is allogeneic hematopoietic stem cell transplantation.Unrelated umbilical cord blood(UCB) is increasingly used as an alternative to bone marrow.The development of NBS in Europe and America has enabled more SCID patients to be diagnosed before symptoms appear, and to enter the normative assessment and intervention procedures as soon as possible. In China SCID has not been included in the NBS program,and there are few units that can diagnose SCID.Patients often delay diagnosis and miss the best period of transplantation. Department of Hematology, Children's Hospital of Fudan University, has used UCBT for the treatment of SCID patients with reduced intensity conditioning(RIC)since 2014.6 of 8 cases were treated with disease-free survival. The encouraging efficacy of these patients suggests that RIC of UCBT may be an effective treatment for SCID patients to urgently hematopoietic stem cell transplantation. The aim of this study is to investigate the efficacy of UCBT in the treatment of SCID, including engraftment rate, disease-free survival rate,overall survival rate and immune reconstitution, and to evaluate transplant-related mortality and complications. All the selected cases are diagnosed as severe combined immunodeficiency disease by immunological function 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) \> 6/8matching,total number of nuclear cells \>5x10\^7/kg.Conditioning: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 prevents Pneumocystis carinii infection after engraftment until half a year after the withdrawal of immunosuppressive agents.

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

Reduced intensity conditioning : Busulphan 3.2mg/kg per day in divided doses for 3 days(total dose 9.6 mg/kg) and cyclophosphamide 50 mg/kg for 2 days (total dose 100 mg/kg).

GVHD prevention: tacrolimus (FK506) 0.1 mg/kg/day, started 4 days before transplantation, is taken orally twice, and the blood concentration is monitored to maintain the concentration at 5-10 ng/ml. If the patient does not have a GVHD transplant +100 days after the slow reduction, until the transplant 6 months after the withdrawal.

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

Eligibility criteria: Inclusion Criteria:

1. All patients were diagnosed as severe combined immunodeficiency disease by immunological function and genetic diagnosis center.
2. Patients have no HLA-matched related donor.
3. Each organ functions normally and conforms the following inspection criteria:

Liver function ALT, AST ≤ 10 times the upper limit of normal value, TBIL ≤ 5 times the upper limit of normal value.

Renal function BUN, Cr ≤ 1.25 times the upper limit of normal value. ECG, cardiac examination normal

Exclusion Criteria:

1. Patients have any contraindications to hematopoietic stem cell transplantation.
2. Patients have other serious diseases, such as serious damage to vital organ function: respiratory failure, cardiac insufficiency, decompensated liver dysfunction, renal insufficiency, uncontrollable infection, etc.
3. The patient is undergoing other drug clinical research.
4. At the same time suffering from other serious acute or chronic physical or mental illness, or laboratory abnormalities, may affect patient safety and compliance, affecting informed consent, research participation, follow-up or interpretation of results.

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
measure: Immune reconstitution
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, master
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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