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

January 25, 2020 updated by: Xiaowen Zhai, Children's Hospital of Fudan University

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

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 were diagnosed as severe combined immunodeficiency disease by immunological function and genetic diagnosis center.

Description

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.

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
UCBT-SCID-Case
SCID patients who underwent cord blood stem cell transplantation.The only curative therapy for SCID is allogeneic hematopoietic stem cell transplantation.
Procedure: cord blood stem cell transplantation
Unrelated cord blood stem cell selection； Reduced intensity conditioning； 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
Immune reconstitution
Time Frame: 3 years after transplantation
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

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
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
Transplant-related mortality
Time Frame: 3 years after transplantation
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

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: 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
  • Study Director: qin maoquan, master, Beijing Children's Hospital

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 20, 2019

First Posted (Actual)

November 21, 2019

Study Record Updates

Last Update Posted (Actual)

January 28, 2020

Last Update Submitted That Met QC Criteria

January 25, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CPBMT-SCID-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

product manufactured in and exported from the U.S.

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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