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

NCT ID: NCT04172181

Last Updated: 2020-01-28

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

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.

Conditions

Severe Combined Immunodeficiency Disease

Study Design

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

Study Groups

UCBT-SCID-Case

SCID patients who underwent cord blood stem cell transplantation.The only curative therapy for SCID is allogeneic hematopoietic stem cell transplantation.

cord blood stem cell transplantation

Intervention Type: PROCEDURE

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

Interventions

cord blood stem cell transplantation

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

Intervention Type: PROCEDURE

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.

• 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

clinical professor

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, master

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

References

van der Burg M, Gennery AR. Educational paper. The expanding clinical and immunological spectrum of severe combined immunodeficiency. Eur J Pediatr. 2011 May;170(5):561-71. doi: 10.1007/s00431-011-1452-3. Epub 2011 Apr 9.

Reference Type: RESULT

PMID: 21479529 (View on PubMed)

Gaspar HB, Qasim W, Davies EG, Rao K, Amrolia PJ, Veys P. How I treat severe combined immunodeficiency. Blood. 2013 Nov 28;122(23):3749-58. doi: 10.1182/blood-2013-02-380105. Epub 2013 Oct 10.

Reference Type: RESULT

PMID: 24113871 (View on PubMed)

Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Hanson IC, Filipovich AH, Jyonouchi S, Sullivan KE, Small TN, Burroughs L, Skoda-Smith S, Haight AE, Grizzle A, Pulsipher MA, Chan KW, Fuleihan RL, Haddad E, Loechelt B, Aquino VM, Gillio A, Davis J, Knutsen A, Smith AR, Moore TB, Schroeder ML, Goldman FD, Connelly JA, Porteus MH, Xiang Q, Shearer WT, Fleisher TA, Kohn DB, Puck JM, Notarangelo LD, Cowan MJ, O'Reilly RJ. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014 Jul 31;371(5):434-46. doi: 10.1056/NEJMoa1401177.

Reference Type: RESULT

PMID: 25075835 (View on PubMed)

Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2005 Feb;115(2):391-8. doi: 10.1016/j.jaci.2004.10.012.

Reference Type: RESULT

PMID: 15696101 (View on PubMed)

Routes JM, Grossman WJ, Verbsky J, Laessig RH, Hoffman GL, Brokopp CD, Baker MW. Statewide newborn screening for severe T-cell lymphopenia. JAMA. 2009 Dec 9;302(22):2465-70. doi: 10.1001/jama.2009.1806.

Reference Type: RESULT

PMID: 19996402 (View on PubMed)

Gatti RA, Meuwissen HJ, Allen HD, Hong R, Good RA. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet. 1968 Dec 28;2(7583):1366-9. doi: 10.1016/s0140-6736(68)92673-1. No abstract available.

Reference Type: RESULT

PMID: 4177932 (View on PubMed)

Antoine C, Muller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, Fasth A, Heilmann C, Wulffraat N, Seger R, Blanche S, Friedrich W, Abinun M, Davies G, Bredius R, Schulz A, Landais P, Fischer A; European Group for Blood and Marrow Transplantation; European Society for Immunodeficiency. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99. Lancet. 2003 Feb 15;361(9357):553-60. doi: 10.1016/s0140-6736(03)12513-5.

Reference Type: RESULT

PMID: 12598139 (View on PubMed)

Fernandes JF, Rocha V, Labopin M, Neven B, Moshous D, Gennery AR, Friedrich W, Porta F, Diaz de Heredia C, Wall D, Bertrand Y, Veys P, Slatter M, Schulz A, Chan KW, Grimley M, Ayas M, Gungor T, Ebell W, Bonfim C, Kalwak K, Taupin P, Blanche S, Gaspar HB, Landais P, Fischer A, Gluckman E, Cavazzana-Calvo M; Eurocord and Inborn Errors Working Party of European Group for Blood and Marrow Transplantation. Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? Blood. 2012 Mar 22;119(12):2949-55. doi: 10.1182/blood-2011-06-363572. Epub 2012 Feb 3.

Reference Type: RESULT

PMID: 22308292 (View on PubMed)

Chiesa R, Gilmour K, Qasim W, Adams S, Worth AJ, Zhan H, Montiel-Equihua CA, Derniame S, Cale C, Rao K, Hiwarkar P, Hough R, Saudemont A, Fahrenkrog CS, Goulden N, Amrolia PJ, Veys P. Omission of in vivo T-cell depletion promotes rapid expansion of naive CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol. 2012 Mar;156(5):656-66. doi: 10.1111/j.1365-2141.2011.08994.x. Epub 2012 Jan 9.

Reference Type: RESULT

PMID: 22224700 (View on PubMed)

Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, Amrolia PJ, Gaspar HB, Davies EG, Friedrich W, Hoenig M, Notarangelo LD, Mazzolari E, Porta F, Bredius RG, Lankester AC, Wulffraat NM, Seger R, Gungor T, Fasth A, Sedlacek P, Neven B, Blanche S, Fischer A, Cavazzana-Calvo M, Landais P; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation; European Society for Immunodeficiency. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010 Sep;126(3):602-10.e1-11. doi: 10.1016/j.jaci.2010.06.015. Epub 2010 Jul 31.

Reference Type: RESULT

PMID: 20673987 (View on PubMed)

Grunebaum E, Mazzolari E, Porta F, Dallera D, Atkinson A, Reid B, Notarangelo LD, Roifman CM. Bone marrow transplantation for severe combined immune deficiency. JAMA. 2006 Feb 1;295(5):508-18. doi: 10.1001/jama.295.5.508.

Reference Type: RESULT

PMID: 16449616 (View on PubMed)

de la Morena MT, Nelson RP Jr. Recent advances in transplantation for primary immune deficiency diseases: a comprehensive review. Clin Rev Allergy Immunol. 2014 Apr;46(2):131-44. doi: 10.1007/s12016-013-8379-6.

Reference Type: RESULT

PMID: 23832379 (View on PubMed)

Castillo N, Garcia-Cadenas I, Barba P, Canals C, Diaz-Heredia C, Martino R, Ferra C, Badell I, Elorza I, Sierra J, Valcarcel D, Querol S. Early and Long-Term Impaired T Lymphocyte Immune Reconstitution after Cord Blood Transplantation with Antithymocyte Globulin. Biol Blood Marrow Transplant. 2017 Mar;23(3):491-497. doi: 10.1016/j.bbmt.2016.11.014. Epub 2016 Nov 22.

Reference Type: RESULT

PMID: 27888015 (View on PubMed)

Williams KM, Hakim FT, Gress RE. T cell immune reconstitution following lymphodepletion. Semin Immunol. 2007 Oct;19(5):318-30. doi: 10.1016/j.smim.2007.10.004. Epub 2007 Nov 19.

Reference Type: RESULT

PMID: 18023361 (View on PubMed)

Walker CM, van Burik JA, De For TE, Weisdorf DJ. Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. Biol Blood Marrow Transplant. 2007 Sep;13(9):1106-15. doi: 10.1016/j.bbmt.2007.06.006.

Reference Type: RESULT

PMID: 17697973 (View on PubMed)

Beck JC, Wagner JE, DeFor TE, Brunstein CG, Schleiss MR, Young JA, Weisdorf DH, Cooley S, Miller JS, Verneris MR. Impact of cytomegalovirus (CMV) reactivation after umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2010 Feb;16(2):215-22. doi: 10.1016/j.bbmt.2009.09.019. Epub 2009 Sep 26.

Reference Type: RESULT

PMID: 19786112 (View on PubMed)

Szabolcs P, Niedzwiecki D. Immune reconstitution in children after unrelated cord blood transplantation. Biol Blood Marrow Transplant. 2008 Jan;14(1 Suppl 1):66-72. doi: 10.1016/j.bbmt.2007.10.016.

Reference Type: RESULT

PMID: 18162223 (View on PubMed)

Uhlin M, Sairafi D, Berglund S, Thunberg S, Gertow J, Ringden O, Uzunel M, Remberger M, Mattsson J. Mesenchymal stem cells inhibit thymic reconstitution after allogeneic cord blood transplantation. Stem Cells Dev. 2012 Jun 10;21(9):1409-17. doi: 10.1089/scd.2011.0310. Epub 2011 Oct 12.

Reference Type: RESULT

PMID: 21861757 (View on PubMed)

Krenger W, Hollander GA. The immunopathology of thymic GVHD. Semin Immunopathol. 2008 Dec;30(4):439-56. doi: 10.1007/s00281-008-0131-6. Epub 2008 Oct 31.

Reference Type: RESULT

PMID: 18974988 (View on PubMed)

Weinberg K, Blazar BR, Wagner JE, Agura E, Hill BJ, Smogorzewska M, Koup RA, Betts MR, Collins RH, Douek DC. Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood. 2001 Mar 1;97(5):1458-66. doi: 10.1182/blood.v97.5.1458.

Reference Type: RESULT

PMID: 11222394 (View on PubMed)

Chung B, Barbara-Burnham L, Barsky L, Weinberg K. Radiosensitivity of thymic interleukin-7 production and thymopoiesis after bone marrow transplantation. Blood. 2001 Sep 1;98(5):1601-6. doi: 10.1182/blood.v98.5.1601.

Reference Type: RESULT

PMID: 11520813 (View on PubMed)

Jimenez M, Martinez C, Ercilla G, Carreras E, Urbano-Ispizua A, Aymerich M, Villamor N, Amezaga N, Rovira M, Fernandez-Aviles F, Gaya A, Martino R, Sierra J, Montserrat E. Reduced-intensity conditioning regimen preserves thymic function in the early period after hematopoietic stem cell transplantation. Exp Hematol. 2005 Oct;33(10):1240-8. doi: 10.1016/j.exphem.2005.06.016.

Reference Type: RESULT

PMID: 16219547 (View on PubMed)

Other Identifiers

CPBMT-SCID-2019

Identifier Type: -

Identifier Source: org_study_id