Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID

Severe Combined Immunodeficiency Disease Clinical Trial

Official title:

Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for Severe Combined Immunodeficiency Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04172181
• Other study ID #: CPBMT-SCID-2019
• Status: Active, not recruiting
• Start date: December 1, 2019
• Est. completion date: October 31, 2023

Study information

• Verified date: January 2020
• Source: Children's Hospital of Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: October 31, 2023
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Severe Combined Immunodeficiency
• Severe Combined Immunodeficiency Disease

Intervention

Procedure:
• cord blood stem cell transplantation
Unrelated cord blood stem cell selection; Reduced intensity conditioning; GVHD prevention; Infection prevention.

Locations

Country	Name	City	State
China	Children's Hospital of Fudan University	Shanghai	Minhang

Sponsors (9)

Lead Sponsor	Collaborator
Children's Hospital of Fudan University	Beijing Children's Hospital, Children's Hospital Of Soochow University, Children’s Hospital of Nanjing Medical University, Guangzhou Women and Children's Medical Center, Shanghai Children's Hospital, Shenzhen Children's Hospital, The First Affiliated Hospital of Zhengzhou University, Wuhan Women and Children's Medical Center

Country where clinical trial is conducted

China, 

References & Publications (22)

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The occurrence of adverse events (AE)	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
Other	The occurrence of graft-versus-host disease (GVHD)	Acute and chronic GVHD is measured and graded as per standardised criteria.	3 years after transplantation
Other	Transplant-related mortality	Transplant-related mortality (TRM)included mortality from any cause other than as a result of the underlying primary immunodeficiency up to day +100 post neutrophil engraftment.	3 years after transplantation
Other	The occurrence of transplant-related complications except GVHD	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
Primary	Overall survival rate	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	Disease free survival rate	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
Secondary	Successful engraftment	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
Secondary	Immune reconstitution	Immune reconstitution is including T-cell and B-cell reconstitution.The variable would be coded as 1 if any of these two cells had been reconstituted while 0 for none. T-cell reconstitution is defined as meeting these criteria: CD3+ cell count > 1000 per cubic millimeter, and CD4+ cell count > 500 per cubic millimeter. B-cell reconstitution is defined as independence from Ig-replacement therapy.	3 years after transplantation